2018 Emerging Science Abstract Presentations

EMERGING SCIENCE PLATFORM SESSION

Tuesday, April 24, 2018, 5:45 p.m. – 7:00 p.m.

001 INTREPID: A Prospective, Double Blinded, Multicenter Randomized Controlled Trial Evaluating Deep Brain Stimulation with a New Multiple Source, Constant Current Rechargeable System in Parkinson's Disease Jerrold L. Vitek, MD, PhD, Minneapolis, MN

002 ABX-1431, A First-in-Class Endocannabinoid Modulator, Improves Tics in Adult Patients with Tourette Syndrome Kirsten Mueller-Vahl, MD, Hannover, Germany

003 Longer-term Assessment of the Safety and Efficacy of Nusinersen for the Treatment of Infantile-onset Spinal Muscular Atrophy (SMA): An Interim Analysis of the SHINE Study Diana Castro, MD, Dallas, TX

004 RG7916 significantly increases SMN Protein in SMA Type 1 Babies Giovanni Baranello, Milano, Italy

005 Effect of fingolimod in pediatric MS: further insights from sensitivity, supportive and post-hoc analyses from PARADIGMS Kumaran Deiva, MD, PhD, Le Kremlin-Bicêtre, France

006 MRI and Relapse Results for ALKS 8700 in Patients with Relapsing Remitting Multiple Sclerosis: 1-year Interim Results from the Phase 3 EVOLVE-MS-1 Study Richard Leigh-Pemberton, MD, Waltham, MA

007 Ezutromid significantly reduced muscle damage whilst maintaining utrophin in patients with Duchenne muscular dystrophy (DMD) after 24-weeks of treatment Francesco Muntoni, MD, London, UK

008 Efficacy, Safety, and Tolerability of Ubrogepant for the Acute Treatment of Migraine: Results from a Single Attack Phase II Study, ACHIEVE I Joel Trugman, Madison, NJ

009 Efficacy and safety of erenumab in episodic migraine patients with 2–4 prior preventive treatment failures: Results from the Phase 3b LIBERTY study Uwe Reuter, Berlin, Germany

EMERGING SCIENCE POSTER PRESENTATIONS

Poster Session IV, Wednesday, April 25, 2018, 11:30 a.m.–7:00 p.m.

P4.466 AVXS-101 Gene Replacement Therapy for SMA Type 1: Pivotal Study (STR1VE) Update John W. Day, MD, PhD, Palo Alto, CA

P4.467 Effect of ZX008 (Fenfluramine HCl Oral Solution) on Total Seizures in Dravet Syndrome Joseph Sullivan, San Francisco, CA

P4.468 Transdermal Cannabidiol (CBD) Gel for the Treatment of Focal Epilepsy in Adults John A. Messenheimer, Jr., MD, Moncure, NC

P4.469 ZX008 (Fenfluramine HCL Oral Solution) in Dravet Syndrome: Effect on Convulsive Seizure Frequency in Subjects Who Failed Treatment with Stiripentol Prior to Study 1 Elaine Wirrell, MD, FAAN, Rochester, MN

P4.470 Eptinezumab Achieved Meaningful Reductions in Migraine Activity As Early As Day 1 and Were Sustained Through Week 12: Results From PROMISE-2 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-2) Phase 3 Trial in Chronic Migraine David B. Kudrow, MD, Santa Monica, CA

P4.471 Eptinezumab Reduced Migraine Frequency and Triptan/Ergotamine Use Over Weeks 1-12, and Improved HIT-6 Scores at Months One and Three: Results From the Phase 3 PROMISE-2 Trial in Chronic Migraine Stephen D. Silberstein, MD, FAAN, Philadelphia, PA

P4.472 Clinical Development of VX15/2503 Anti-Semaphorin 4D Antibody as a Potential Treatment for Huntington’s Disease Elizabeth Evans, PhD, Rochester, NY

P4.473 A Randomized Trial of Deferiprone for Pantothenate Kinase-Associated Neurodegeneration (on behalf of the TIRCON Group) Thomas H. Klopstock, MD, Munich, Germany

P4.474 Non-Invasive Peripheral Nerve Stimulation for Symptomatic Relief of Hand Tremor in Essential Tremor Rajesh Pahwa, MD, FAAN, Kansas City, KS

P4.475 Natalizumab extended interval dosing (EID) is associated with a significant reduction in progressive multifocal leukoencephalopathy (PML) risk compared with standard interval dosing (SID) in the TOUCH® Prescribing Program Lana Zhovtis Ryerson, MD, New York, NY

P4.476 Withdrawn

P4.477 Autologous Haematopoietic Stem Cell Transplantation in Treatment Naïve Patients with ‘Aggressive’ Multiple Sclerosis Joyutpal Das, MBBS, Sheffield, UK

P4.478 B Cell Targeted Treatment in Myasthenia Gravis (BeatMG) - A Phase 2 Trial of Rituximab in Myasthenia Gravis: Topline Results Richard J. Nowak, MD, New Haven, CT

CLINICAL TRIALS PLENARY SESSION

Tuesday, April 24, 2018, 9:15 a.m.–11:30 a.m.

A double-blind placebo-controlled study to evaluate the safety and efficacy of FcRn-antagonist ARGX-113 (efgartigimod) in generalized myasthenia gravis James F. Howard, Jr., MD, FAAN, Chapel Hill, NC

A Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab for the Preventive Treatment of Chronic Migraine: Results of the PROMISE-2 (Prevention of Migraine via Intravenous Eptinezumab Safety and Efficacy 2) Trial Richard B. Lipton, MD, FAAN, Bronx, NY

001

5:45 p.m. – 5:48 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

INTREPID: A Prospective, Double Blinded, Multicenter Randomized Controlled Trial Evaluating Deep Brain Stimulation with a New Multiple Source , Constant Current Rechargeable System in Parkinson's Disease

Jerrold L. Vitek, MD, PhD; Cathrin Beutefisch; Andrew Duker; Jennifer Durphy; Kelly Foote; Monique Giroux; Michal Gostkowski; Robert Gross; Jonathan Jagid; Suketu Khandhar; Paul Larson; Timothy Leichliter; Luca Corneliu; Andre Machado; Adam Mamelak; Alon Mogilner; Guillermo Moguel-Cobos; Jules Nazzaro; Michael Okun; Jill Ostrem; Rajesh Pahwa; Michael C. Park; Fenna Phibbs; Julie Pilitsis ; Fracisco Ponce; Michael Pourfar; Gonzalo Revuelta; Joshua Rosenow; Sepehr Sani; Lauren Schrock; Mark Sedrak; Mustafa Siddiqui; Philip Starr; Mariel Szapiel; Michele Tagliati; Istvan Takacs; Stephen Tatter; Alexander Troster; Ryan Uitti; Leonard Verhagen; Jerrold Vitek; Robert Wharen; Donald Whiting; Hong Yu; Cindy Zadikoff; Lilly Chen, MD; Roshini Jain, MS

Objective: INTREPID is designed to assess the improvement in motor function and quality of life in patients with Parkinson's disease (PD) following Deep Brain Stimulation (DBS) using a new device with multiple independent current sources that allowed for activation of individual contacts on the DBS lead thereby permitting a defined distribution of applied current. Background: DBS is an effective treatment for the motor signs and fluctuations associated with PD. Although DBS efficacy has been substantiated by several randomized controlled trials (RCT), the degree of improvement varies significantly. The INTREPID Study assessed improvement in motor function and quality of life in PD patients following bilateral subthalamic nucleus (STN) DBS using a new device with multiple independent current sources. Design/Methods: INTREPID is a multicenter, prospective, double blinded RCT sponsored by Boston Scientific. Subjects were implanted bilaterally in the STN with a multiple source constant current DBS System (Vercise System). Blinded subjects were randomized to either receive active versus control settings for a 12-week period. All assessments were completed by a blinded assessor. Following the blinded period, subjects received their best therapeutic settings. Improvement in motor function and quality of life was evaluated using a PD diary, UPDRS, PDQ-39, and a battery of neuropsychological assessments. Adverse events were recorded. Results: The study successfully met the primary endpoint (p < 0.001) with a mean difference of 3.03 ± 4.2 hours from baseline to 12 weeks between the active and the control group in ON time (PD Diary), with no increase in antiparkinsonian medications. The study also met several of the secondary endpoints. The incidence of infection was 2.7% and peri-operative intracranial hemorrhage was 1%. Conclusions: The results of the INTREPID Study demonstrate that the use of a multiple source, constant-current DBS system is safe and effective in the treatment of Parkinson's disease symptoms.

Study Supported By: Boston Scientific

Disclosures: Dr. Vitek has received personal compensation for activities with Abbott, Boston Scientific, Medtronic, NeuroNexus, and Great Lakes NeuroTechnologies Inc. as a consultant and/or speaker. Dr. Vitek has received research support from Boston Scientific, NIH, Medtronic and Abbott. Dr. Vitek owns stock in SIS. Dr. Beutefisch has nothing to disclose. Dr. Duker has nothing to disclose. Dr. Durphy has nothing to disclose. Dr. Foote has nothing to disclose. Dr. Giroux has received personal compensation as a speaker with WorldMeds, Lundbeck and Adamas. Dr. Giroux has received research support from Boston Scientific and Cala Health. Dr. Gostkowski has nothing to disclose. Dr. Gross has nothing to disclose. Dr. Jagid has nothing to disclose. Dr. Khandhar has nothing to disclose. Dr. Larson has received personal compensation for advisory board and other activities with Medtronic, Abbott and Galvani. Dr. Larson has received research support from Voyageur Therapeutics. Dr. Leichliter has nothing to disclose. Dr. Luca has received personal compensation as a consultant for Medtronic and Abbott. Dr. Machado has nothing to disclose. Dr. Mamelak has received personal compensation as a consultant with Medtronic, Abbott (St Jude Medical) and Blaze Bioscience. Dr. Mamelak holds stock and/or stock options in Blaze Bioscience. Dr. Mogilner has received personal compensation as a consultant with Boston Scientific, Medtronic and Abbott (St Jude Medical). Dr. Mogliner has received research support from Boston Scientific and Abbott (St Jude Medical). Dr. Moguel-Cobos has nothing to disclose. Dr. Nazzaro has nothing to disclose. Dr. Okun has nothing to disclose. Dr. Ostrem has received personal compensation for consulting with Adamas and Neurocrine. Dr. Ostrem has received research support from the Michael J. Fox Foundation, Boston Scientific, Medtronic, Cala Health, and the DOD Defense Advanced Research Projects Agency. Dr. Pahwa has received consulting fees from Abbvie, ACADIA, Acorda, Adamas, Cynapses, Global Kinetics, Lundbeck, Neurocrine, Pfizer, Sage, Sunovion, Teva Neuroscience, and US World Meds. Dr. Pahwa has received personal compensation in an editorial capacity as the Co-Editor-In-Chief of the International Journal of Neuroscience. Dr. Pahwa has received research support from Abbvie, Adamas, Avid, Biotie, Boston Scientific, Cala Health, Civitas, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group and Pfizer. Dr. Park has received personal compensation for activities including consulting with Medtronic, Zimmer Biomet, and SmartimplantSystems. Dr. Park has received research support from Medtronic, Boston Scientific, Advanced Neuromodulation Systems, Inc., and St Jude Medical. Dr. Phibbs has received personal compensation for consulting with Medtronic. Dr. Pilitsis has received personal compensation for activities including speaking and consulting with Boston Scientific, Jazz Pharmaceuticals, Centauri, Karuna, Medtronic, and Abbott. Dr. Pilitsis hold stock and/or stock options in Centauri and Karuna. Dr. Pilitsis has received research support from Jazz Pharmaceuticals, Nevro, NIH, GE Global Research, Boston Scientific, Medtronic, and Abbott. Dr. Ponce is a consultant for Medtronic and has received personal compensation from the Barrow Center for Neuromodulation. Dr. Pourfar has nothing to disclose. Dr. Revuelta has nothing to disclose. Dr. Rosenow has received personal compensation and research support from Boston Scientific. Dr. Sani has nothing to disclose. Dr. Schrock has nothing to disclose. Dr. Siddiqui has received research support from Boston Scientific, Abbvie, Sunovion, Accord Therapies, and Elly Lily. Dr. Szapiel has nothing to disclose. Dr. Tagliati has nothing to disclose. Dr. Takacs has nothing to disclose. Dr. Tatter has nothing to disclose. Dr. Troster has received personal compensation for activities including consulting with Axovant, Boston Scientific, Medtronic, Takeda and Voyager. Dr. Troster has received research support from the Barrow Neurological Foundation. Dr. Uitti has nothing to disclose. Dr. Verhagen has received personal compensation for consulting with Abbott and Abbvie. Dr. Verhagen has received research support from Boston Scientific, Medtronic, Abbott, AbbVie, Neuroderm, Pfizer, Adamas, and Worldmeds. Dr. Wharen has nothing to disclose. Dr. Whiting has nothing to disclose. Dr. Yu has nothing to disclose. Dr. Zadikoff has received personal compensation for consulting with Abbvie, Abbott (St Jude), Merz, UCB, USWorldMeds, Acadia, and Teva. Dr. Zadikoff has received research support from AbbVie, Allergan and Abbott (St Jude). Dr. Chen is a full-time employee of Boston Scientific. Dr. Jain is a full-time employee of Boston Scientific. Dr. Starr has received personal compensation for activities with Boston Scientific and Medtronic. Dr. Starr has received research support from Boston Scientific and Medtronic.

002

5:48 p.m. – 5:51 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

ABX-1431, A First-in-Class Endocannabinoid Modulator, Improves Tics in Adult Patients with Tourette Syndrome

Kirsten Mueller-Vahl, MD; Ewgeni Jakubovski, Clinical Psychologist, MA; Fremer Carolin, MD; Katja Kunert, MD; Chan Beals, MD, PhD; Danielle Bocchino; Evan Friedman; Forrest Hull; Alan Ezekowitz, MD, PhD; Marcus May, PhD; Christoph Schindler, PhD

Objective: An inhibitor of the major clearance pathway of the primary endocannabinoid in the human brain (2-arachidonoylglycerol (2-AG)) was used to study the effects of elevating endocannabinoid tone in TS. Background: TS is a neurodevelopmental condition characterized by motor and vocal tics with onset in childhood. ABX-1431 is a first-in-class, oral, highly selective inhibitor of the enzyme monoacylglycerol lipase (MGLL) that raises nervous system concentrations of the endocannabinoid 2-AG, which acts as an agonist on presynaptic central cannabinoid (CB1) receptors. Since 2-AG exerts feedback inhibition on neurotransmitter release, and MGLL in abundant in the basal ganglia, ABX-1431 may improve tics and comorbidities in TS. Design/Methods: 20 adult patients (16 men, 4 women, age 18-54) with moderate-severe TS were treated in a single-dose crossover study with 40 mg ABX-1431 or placebo. Endpoints were tic severity according to the Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS), the Modified Rush Video-Based Tic Rating Scale (MRVS), and the self-assessment Adult Tic Questionnaire (ATQ), and premonitory urges according to the Premonitory Urge for Tics Scale (PUTS). Results: Patients displayed a placebo-adjusted ABX-1431-related tic improvement in the YGTSS-TTS at 8 hours (p=0.0384), with improvement in motor tics at 4 hours (p=0.0016) and 8 hours (p=0.0049), and a reduction in self-reported tic intensity (ATQ) at 4 hours (p=0.0005) and 8 hours (p=0.0008). A placebo-adjusted ABX-1431-related improvement in premonitory urges was observed at 4 hours (PUTS, p=0.0369), while no significant difference was observed with the MRVS. The most common adverse events were headache, somnolence, and fatigue, which resolved. Conclusions: Our data suggest that modulation of the endocannabinoid system by selective inhibition of MGLL improves tics in TS. ABX-1431 may provide a unique treatment profile for TS, and holds promise as a novel mechanism to treat movement disorders and neuropsychiatric conditions.

Study Supported By:

Disclosures: Dr. Mueller-Vahl has received personal compensation for consulting and/or serving on a scientific advisory board with Abide Therapeutics, Therapix Biosciences and CannaFoundation. Dr. Mueller-Vahl has received research support from GW Pharmaceuticals, Almirall, Abide Therapeutics and Therapix Biosciences. Dr. Jakubovski has nothing to disclose. Dr. Carolin has nothing to disclose. Dr. Kunert has nothing to disclose. Dr. Beals is an employee of Abide Therapeutics and has received stock options in the company. Dr. Bocchino is an employee of Abide Therapeutics and has received stock options in the company. Dr. Friedman is an employee of Abide Therapeutics and has received stock options in the company. Dr. Hull is an employee of Abide Therapeutics and has received stock options in the company. Dr. Ezekowitz is an employee of Abide Therapeutics and has received stock options in the company. Dr. Ezekowitz has received compensation for serving on the Board of Directors of Fulcrum. Dr. May has nothing to disclose. Dr. Schindler has nothing to disclose.

003

5:51 p.m. – 5:54 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Longer-term Assessment of the Safety and Efficacy of Nusinersen for the Treatment of Infantile-onset Spinal Muscular Atrophy (SMA): An Interim Analysis of the SHINE Study

Diana Castro, MD; Michelle A. Farrar; Richard Finkel, MD; Mar Tulinius; Kristin Krosschell; Kayoko Saito; Yiwei Zhang; Ishir Bhan; Wildon Farwell; Sandra P. Reyna

Objective: To present interim results from the SHINE study (NCT02594124) for patients with infantile-onset SMA (most likely to develop Type I) who transitioned from ENDEAR. Background: Nusinersen is an antisense oligonucleotide approved for the treatment of SMA. It has demonstrated a favorable benefit:risk profile and shown significant and clinically meaningful efficacy on motor function across a broad spectrum of SMA populations, and time to death or permanent ventilation (EFS) in infantile-onset SMA. Design/Methods: SHINE is an open-label extension study for infants/children who participated in the ENDEAR, CHERISH, CS12 or CS3A nusinersen trials. Nusinersen doses were administered according to the regimen and participant’s cohort from the previous trial. Primary endpoint is safety/tolerability; secondary endpoints include achievement of HINE Section 2 motor milestones, and EFS. Results: The cutoff date was June 30, 2017; 89 patients transitioned from ENDEAR, 65/81 previously randomized to nusinersen and 24/41 to sham-control. Within SHINE only, 83 patients had an adverse event (AE). There were no treatment-related serious AEs. The most frequent AEs were pyrexia and upper respiratory tract infection. Mean (95% CI) change in HINE-2 total score from nusinersen initiation to last observed visit was 1.1 (0.20–1.90) for patients who received sham-control in ENDEAR and nusinersen in SHINE (n=20/24) and 5.8 (4.58–7.04) for those who received nusinersen in ENDEAR and SHINE (n=74/81; pooled ENDEAR/SHINE data). Median (95% CI) EFS time among patients treated with sham-control in ENDEAR was 22.6 (13.6–31.3) weeks versus 73.0 (36.3–NA) weeks among those who received nusinersen in ENDEAR and SHINE. Conclusions: Improvements in motor function and EFS continued among patients who initiated nusinersen in ENDEAR and motor function improved among those who initiated nusinersen in SHINE. Further analysis of SHINE data will provide additional information on the long-term safety/tolerability and efficacy of repeated nusinersen doses across multiple SMA populations.

Study Supported By: Biogen

Disclosures: Dr. Castro has received personal compensation for activities compensation for serving on scientific advisory boards with Marathon and Sarepta. Dr. Castro has received research support from Bigoen, Sarepta, ReveraGen Biopharma, and FibroGen. Dr. Farrar has received personal compensation for serving on a scientific advisory board with Biogen. Dr. Finkel has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ionis Pharmaceuticals, Inc., Biogen, AveXis, Novartis, Roche, CureSMA, SMA Europe, the SMA Foundation and SMA Reach (UK). Dr. Finkel has received research support from Ionis Pharmaceuticals, Inc., AveXis, Roche and Cytokinetics. Dr. Tulinius has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Biomarin and PTC. Dr. Krosschell has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Cytokinetics. Dr. Krosschell has received research support from Ionis, Biogen and Cytokinetics. Dr. Saito has received personal compensation for serving on scientific advisory boards with Biogen and Roche/Chugai. Dr. Saito has received research support from Biogen, Roche/Chugai and Ionis. Dr. Zhang is an employee of Biogen and holds stock/stock options in the company. Dr. Bhan is an employee of Biogen and holds stock/stock options in the company. Dr. Farwell is an employee of Biogen and holds stock/stock options in the company. Dr. Reyna is an employee of Biogen and holds stock/stock options in the company.

004

5:54 p.m. – 5:57 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

RG7916 significantly increases SMN Protein in SMA Type 1 Babies

Giovanni Baranello; Heidemarie Kletzl; Yumi Cleary; Gillian Armstrong; John Day, MD, PhD; Andrea Klein; Eugenio Mercuri; Laurent Servais; Nicholas Deconinck; Riccardo Masson; Tim Seabrook; Christian Czech; Marianne Gerber; Fung Lee; Kristina Gelblin; Stephane Nave; Ksenija Gorni; Omar Khwaja, MD

Objective: Interim SMN protein data from FIREFISH Part 1 are presented for the first time. FIREFISH (NCT02913482) is a multi-center, open-label, seamless study of RG7916 (RO7034067) in babies aged 1–7 months with Type 1 spinal muscular atrophy (SMA) and two SMN2 gene copies. Background: SMA is a severe, progressive, inherited disease that leads to loss of motor function and is the leading genetic cause of mortality in infants and toddlers. SMA is caused by reduced levels of SMN protein due to deletions or mutations of the survival of motor neuron 1 (SMN1) gene and alternative splicing of a related SMN2 gene. The published median time to death or permanent ventilation in Type 1 patients with two SMN2 gene copies is 10.5 months of age (Finkel, Neurology 2014). RG7916 is an orally administered, centrally and peripherally distributed small molecule that modulates SMN2 pre-mRNA splicing to increase SMN protein. Design/Methods: The exploratory Part 1 (n=8–24) of the FIREFISH study assesses safety, tolerability, pharmacokinetics and pharmacodynamics of RG7916 at different dose levels. The confirmatory Part 2 (n=40) will assess safety and efficacy of RG7916. Results: A dose-dependent increase in SMN protein levels in blood was observed, with an up to 6.5 -fold increase versus baseline after 4 weeks of treatment at the highest dose of RG7916 (range 2.0 – 6.5). To date, no safety-related stopping rules have been met, and while follow up was limited, no patient lost the ability to swallow, required tracheostomy, or reached permanent ventilation. Updated survival data will be presented. Conclusions: The up to 6.5-fold increase in SMN protein observed in FIREFISH Part 1 compares favorably with the approximately 2-fold difference in SMN protein levels between SMA severity types (e.g., Type 2 vs. Type 1). All doses explored so far have been well tolerated. FIREFISH is currently recruiting globally.

Study Supported By: F. Hoffmann-La Roche

Disclosures: Dr. Baranello has nothing to disclose. Dr. Kletzl is an employee of F. Hoffmann-La Roche and holds stock/stock options in the company. Dr. Cleary is an employee of F. Hoffmann-La Roche. Dr. Armstrong is an employee of F. Hoffmann-La Roche and hold stock/stock options in the company. Dr. Day has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Ionis Pharmaceuticals, Roche Pharmaceuticals, Cytokinetics, Pfizer, AveXis, AMO Pharmaceuticals, Sarepta Therapeutics, and Santhera Pharmaceuticals. Dr. Day has received (royalty or license fee or contractual rights) payments from Athena Diagnostics. Dr. Day has received research support from Biogen, Ionis Pharmaceuticals, Cytokinetics, Roche Pharmaceuticals, aTyr, AveXis, Bristol Meyers Squibb, Sanofi-Genzyme, AMO Pharmaceuticals and Sarepta Therapeutics. Dr. Klein has received personal compensation for speaking and consulting with Biogen and Santhera. Dr. Mercuri has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Roche, Ionis, Biogen, Avexis and Novartis. Dr. Mercuri has received research support from Italian Telethon, Famiglie SMA Italy and SMA Europe. Dr. Servais has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Avexis, Sarepta, Dynacure, Pfizer and Servier. Dr. Servais has received research support from Roche, Valerion and Dynacure. Dr. Deconick has received personal compensation for activities, compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Sarepta. Dr. Masson has nothing to disclose. Dr. Seabrook is an employee of F. Hoffmann-La Roche. Dr Czech is an employee of F. Hoffmann-La Roche and hold stock/stock options in the company. Dr. Gerber is an employee of F. Hoffmann-La Roche and holds stock/stock options in the company. Dr. Lee has nothing to disclose. Dr. Gelblin is an employee of F. Hoffmann-La Roche. Dr. Nave is an employee of F. Hoffmann-La Roche. Dr. Gorni is an employee of F. Hoffmann-La Roche. Dr. Khwaja is an employee of F. Hoffmann-La Roche.

005

5:57 p.m. – 6:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Effect of fingolimod in pediatric MS: further insights from sensitivity, supportive and post-hoc analyses from PARADIGMS.

Kumaran Deiva, MD, PhD; Peter Huppke; Brenda Banwell, MD, FAAN; Tanuja Chitnis, MD, FAAN; Jutta Gaertner, MD; Lauren Krupp, MD, FAAN; Emmanuelle Waubant, MD, FAAN; Tracy Stites, PhD; Gregory Lewis Pearce; Martin Merschhemke

Objective: To further evaluate the effect of fingolimod versus interferon (IFN) β-1a in pediatric multiple sclerosis (MS), excluding IFN antibody-positive patients, in treatment-naïve patients, and on disability progression up to 2 years. Background: In PARADIGMS, a double-blind phase III trial of 215 pediatric MS patients (age 10–<18 years), fingolimod administered up to 2 years significantly reduced both the annualized relapse rate (ARR) (primary endpoint) and the rate of new/newly enlarged T2 (n/neT2) lesions (key secondary endpoint) compared to IFN β-1a. Design/Methods: Predefined analyses of the endpoints were performed after excluding patients in the IFN β-1a arm who were IFN neutralizing antibody (Nabs)-positive at study end (sensitivity analysis) and in disease-modifying therapy (DMT)-naïve patients (supportive analysis). A post-hoc evaluation of 3-month confirmed disability progression (3M-CDP) was also conducted. Results: Excluding Nabs-positive IFN β-1a patients (n=9) did not have any tangible impact on the primary and key secondary results (81.5% ARR reduction and 47.6% reduction in n/neT2 lesions, both p<0.001, versus 81.9% and 52.6% in the overall population, respectively). At baseline, 63.3% of patients were treatment naïve. The effect of fingolimod treatment in the DMT-naïve subpopulation (85.8% ARR reduction and 53.4% n/neT2 lesion reduction versus IFN β-1a, both p<0.001) was also consistent with the overall patient population. The Kaplan–Meier estimate of the percentage of patients without 3M-CDP up to 2 years was higher in the fingolimod group (95.2%) compared with the IFN β-1a group (84.7%) (p=0.015), with a risk reduction in 3M-CDP of 77.2% (hazard ratio=0.23, p=0.007). 3M-CDP sustained until the last observation yielded similar results. Expanded disability status scale (EDSS) measurements at different time points will be presented. Conclusions: Fingolimod in pediatric MS was associated with consistent control of disease activity across sensitivity/supportive analyses, and benefits on disability progression were observed over the treatment duration of up to 2 years.

Study Supported By: Novartis

Disclosures: Dr. Deiva has received personal compensation for speaking activities with Novartis. Dr. Huppke has received personal compensation for activities such as serving on a scientific advisory board and speaking with Novartis and Bayer Health Care. Dr. Banwell has received personal compensation for serving as a central MRI reviewer for the present trial with Novartis. Dr. Chitnis has received personal compensation for advisory boards/consulting with F. Hoffman-La Roche, Biogen and Novartis. Dr Chitnis has received financial support for research activities from Biogen, Merck Serono, Verily and Novartis. Dr. Jutta Gärtner in the last three years has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer, Teva and Novartis. Dr. Jutta Gärtner has received research support from Novartis and Biogen. Dr. Krupp has received personal compensation for activities as a speaker, consultant and/or participant on an advisory board from Biogen Idec, Novartis, Teva Neurosciences and Multicell. Dr. Krupp has received royalty or license fees from ER Squibb & Sons, Avenir, Johnson & Johnson and Osmotica. Dr. Krupp has received research support from Novartis, Biogen Idec, Celgene Corporation and Genentech. Dr. Waubant has received research support from Roche, Biogen Idec and Novartis. Dr. Stites is an employee with Novartis Pharmaceuticals Corporation. Dr. Pearce is an employee with Novartis Pharmaceuticals Corporation. Dr. Merschhemke is an employee with Novartis Pharmaceuticals Corporation.

006

6:00 p.m. – 6:03 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

MRI and Relapse Results for ALKS 8700 in Patients with Relapsing Remitting Multiple Sclerosis: 1-year Interim Results from the Phase 3 EVOLVE-MS-1 Study

Richard Leigh-Pemberton, MD; Robert Naismith; Boris Kandinov; David Rezendes; Narinder Nangia; Maria Lopez-Bresnahan, MD, PhD; Douglas Arnold, MD; Jerry Wolinsky, MD, FAAN

Objective: To report 1-year MRI and relapse results for patients with relapsing-remitting multiple sclerosis (RRMS) treated with ALKS 8700 (also known as BIIB098) in EVOLVE-MS-1. Background: ALKS 8700 is a prodrug of monomethyl fumarate (MMF), the active metabolite of dimethyl fumarate (DMF). DMF is approved for relapsing forms of multiple sclerosis (RMS). ALKS 8700 is being developed as an oral disease-modifying therapy for RMS and is designed to treat MS with the same active metabolite as DMF but with potentially improved gastrointestinal tolerability. Two Phase 3 studies are currently evaluating ALKS 8700 in patients with RRMS: EVOLVE-MS-1, a long-term safety and tolerability study of ALKS 8700, and EVOLVE-MS-2, a 5-week, head-to-head study comparing the gastrointestinal tolerability of ALKS 8700 and DMF. Design/Methods: EVOLVE-MS-1 is a multi-center, prospective, open-label, single-arm Phase 3 study to assess long-term safety, tolerability, and treatment effect of ALKS 8700 462 mg twice daily in approximately 900 patients with RRMS. Inclusion criteria: age 18-65 years with RRMS (McDonald criteria 2010) and EDSS 6.0. We present an exploratory interim report from November 2017 of annualized relapse rate (ARR) and MRI parameters. Results: ARR was 0.16 for the 570 patients (493.6 patient-years) evaluated during this interim analysis. Interim MRI results included 152 patients who completed MRI assessments at 1 year. Mean numbers (SD) of new/enlarging T2 lesions, gadolinium-enhancing (Gd+) lesions, and new T1-hypointense lesions were 2.8 (5.9), 0.3 (1.1), and 1.8 (4.2), respectively. With ALKS 8700 treatment there was a significant reduction (p<0.0001) in the number of Gd+ lesions from baseline (mean 1.2 [SD 4.1]) to 1 year (0.3 [1.1]). Conclusions: ALKS 8700 is a novel, oral, prodrug of MMF in Phase 3 development for the treatment of RRMS. These preliminary findings suggest ALKS 8700 may be an effective oral treatment option for patients with RRMS.

Study Supported By: Alkermes, Inc. Development program for ALKS 8700 now supported under a collaboration agreement with Biogen

Disclosures: Dr. Leigh-Pemberton is an employee of Alkermes, Inc. Dr. Naismith has received personal compensation for consulting/speaking with Acorda, Alkermes, Bayer, Biogen, Genentech, Genzyme, EMD Serono, Novartis and Teva. Dr. Naismith has received personal compensation in an editorial capacity for NEJM Journal Watch. Dr. Naismith has received research support from NIH and NMSS. Dr. Kandinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Rezendes has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Nangia has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes. Dr. Nangia has received compensation for serving on the Board of Directors of Alkermes. Dr. Lopez-Bresnahan is an employee of Alkermes. Dr. Arnold has served on advisory boards, received speaker honoraria, served as a consultant for or received research support from Bayer, Biogen, Coronado Biosciences, Consortium of Multiple Sclerosis Centers, Eli Lilly, EMD Serono, Genentech, Genzyme, GlaxoSmithKline, Merck Serono, MS Forum, NeuroRx Research, Novartis, Opexa Therapeutics, Roche, S.A. Serono Symposia International Foundation, Teva, the Canadian Institutes of Health Research and Multiple Sclerosis Society of Canada. Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Acetilon, Alkermes, Biogen, Bionest, Clene Nanomedicine, EMD Serono, Forward Pharma A/S, MedDay Pharmaceuticals, Novartis, Otsuka, Roche/Genentech, PTC Therapeutics and Sanofi Genzyme. Dr Wolinsky has received royalties for monoclonal antibodies outlicensed to Chemicon International through the University of Texas Health Science Center at Houston.

007

6:03 p.m. – 6:06 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Ezutromid significantly reduced muscle damage whilst maintaining utrophin in patients with Duchenne muscular dystrophy (DMD) after 24-weeks of treatment

Francesco Muntoni, MD; Gary Layton, MSc; Indranil Bhattacharya, PhD; Crystal Faelan, PhD; Anne C. Heatherington, PhD; David Roblin, MD, FRCp, FFPM, FMedSci; Jon Tinsley, PhD; Kay Davies, CBE, FRS, FMedSci

Objective: To share results from interim analysis for ezutromid, a first-in-class utrophin modulator which has the potential to treat all patients with DMD Background: Utrophin is a naturally occurring protein that may act as a functional replacement for dystrophin. It is hypothesized that continuous expression in mature muscle fibers could modify the course of DMD (Tinsley et al, 1998). Design/Methods: PhaseOut DMD is a Phase 2 open-label study of ezutromid administered to 40 ambulatory patients with DMD. Primary endpoints (48 week) are MRS assessments. Key secondary endpoints are from muscle biopsy; to be collected at baseline (n=40) and week 24 (n=25) or 48 (n=15). Safety, pharmacokinetics and functional measures are monitored throughout. The interim analysis was planned to assess impact on muscle health, primarily by biopsy; mixed effect models were used to estimate, with 95% confidence intervals, the changes from baseline (least square means difference [LSMD]). Results: A statistically significant reduction in %fibres expressing developmental myosin (MHCd) was observed (from 11.37% to 8.76%, LSMD -2.62% CI, -4.33, -0.90); a relative reduction of 23%. Mean utrophin intensity was maintained and even increased (relative +7%) (0.370 to 0.396, LSMD 0.026 95% CI, -0.005, 0.058). MRS indicated an increase in mean fat fraction (vastus lateralis: from 14.7% to 18.5% n=37) but a decrease in relaxation time (T2) (soleus: from 31.85 to 30.99 msec, n=38). No patient lost ambulation and there were no meaningful decreases in functional performance (eg 6MWD: baseline 404m, 24 weeks: 395m, n=39). All patients achieved plasma levels sufficient to modulate utrophin. Ezutromid continues to be safe and well tolerated. Conclusions: Decreased MHCd, a marker of regeneration, indicates reduction in muscle damage. Utrophin levels were maintained and even increased which, with decreasing MHCd, provides evidence of target engagement. These results support the utrophin hypothesis and the potential for universal treatment for DMD. With PhaseOut DMD StudyGroup

Study Supported By:

Disclosures: Dr. Muntoni has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Summit Therapeutics, Santhera, Pfizer, Sarepta, EU FP7 and Esperare. Dr. Layton has received personal compensation as a consultant to Summit (Oxford) Ltd. Dr. Bhattacharya is an employee and shareholder of Summit Therapeutics and Pfizer Ltd. Dr. Faelan is an employee of Flagship Biosciences which does contract work for Summit Therapeutics. Dr. Heatherington is an employee and shareholder at Summit Therapeutics and Pfizer Ltd. Dr. Roblin is an employee and shareholder at Summit Therapeutics. Dr. Tinsley is an employee and shareholder at Summit Therapeutics. Dr. Davies has received personal compensation for serving on a scientific advisory board with Summit Therapeutics. Dr. Davies has received personal compensation in an editorial capacity for Human Molecular Genetics (Oxford University Press). Dr. Davies has received personal compensation for serving on the Board of Directors of Biotech Growth Trust and UCB Pharmaceuticals. Dr. Davies has received royalty payments from Summit Therapeutics. Dr. Davies has received research support from Summit Therapeutics.

008

6:06 p.m. – 6:09 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Efficacy, Safety, and Tolerability of Ubrogepant for the Acute Treatment of Migraine: Results from a Single Attack Phase II Study, ACHIEVE I

Joel Trugman; Michell Finnegan; Richard Lipton, MD, FAAN; David Dodick, MD, FAAN; Kaifeng Lu; Hassan Lakkis; Armin Szegedi

Objective: To evaluate the efficacy, safety, and tolerability of ubrogepant (50mg, 100mg) versus placebo for the acute treatment of a single migraine attack. Background: Calcitonin gene-related peptide (CGRP) and its receptors are expressed in regions of the nervous system associated with migraine pathophysiology. Ubrogepant is a novel, oral CGRP receptor antagonist in development for the acute treatment of migraine. Design/Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, Phase III study (NCT02828020; ACHIEVE I). Adult patients with a history of migraine (with/without aura) were randomized (1:1:1) to placebo, ubrogepant 50mg, or ubrogepant 100mg. Patients had up to 60 days to treat a single migraine attack of moderate/severe headache pain intensity. Co-primary efficacy endpoints were pain freedom 2 hours after initial dose and absence of the most bothersome migraine-associated symptom (MBS), identified at the time of the treated attack, 2 hours after initial dose. Safety and tolerability were evaluated. Results: 1672 patients were randomized, 1436 were in the safety population, and 1327 were included in the mITT efficacy analysis. Mean age was 40.7 years; majority Caucasian (82.4%) and female (87.5%). The MBS identified at the time of treatment were photophobia (56.4%), phonophobia (22.3%) and nausea (20.9%). At 2-hours post-initial dose, the percentage of ubrogepant-treated patients achieving pain freedom was significantly greater than those treated with placebo (50mg: 19.2%, p=0.0023; 100mg: 21.2%, p=0.0003, placebo: 11.8%). Similarly, the percentage of ubrogepant-treated patients achieving absence of MBS was significantly greater than placebo (50mg: 38.6%, p=0.0023, 100mg: 37.7%, p=0.0023, placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs within 48 hours of dosing were nausea, somnolence, and dry mouth, all with an incidence <5%. Conclusions: In the ACHIEVE I study, both co-primary efficacy endpoints were met with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well-tolerated with no identified safety concerns.

Study Supported By: Allergan plc

Disclosures: Dr. Trugman holds stock and/or stock options in Allergan plc. Dr. Finnegan is a full-time employee of Allergan plc. Dr Lipton has received honoraria from Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Boston Scientific, Bristol Myers Squibb, Colucid, Dr. Reddys, Eli Lilly, eNeura Therapeutics, GlaxoSmithKlein, Merck, Pernix, Novartis, Pfizer, Supernus, Teva, Trigemina, Vector and Vedanta. Dr. Lipton holds stock options in eNeura Therapeutics (a company without commercial products). Dr. Dodick has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Allergan, Amgen, Alder, Merck, Dr Reddy’s, Promius, eNeura, Eli Lilly & Company, Insys therapeutics, Autonomic Technologies, Teva, Xenon, Tonix, Trigemina, Boston Scientific, GBS, Colucid, Zosano, Laydenburg Thalmann, Biocentric, Biohaven, Magellan, Pfizer (Japan) and Charleston Laboratories. Dr. Dodick has received personal compensation for serving in an editorial capacity for CME Companies, Chameleon Communications, Medscape, WebMD, Academy for Continued Healthcare Learning, Haymarket Medical Education, Miller Medical Communications, Global Scientific Communications, Meeting LogiX and Health LogiX. Dr. Dodick has received (royalty or license fee or contractual rights) payments from Oxford University Press and Cambridge University Press. Dr. Dodick holds stock and/or stock options in Nocira and Second Opinion. Dr. Lu is an employee and stockholder of Allergan. Dr. Lakkis is a full-time employee of Allergan. Dr. Szegedi is a full-time employee of Allergan. Dr. Szegedi is a stockholder of Allergan and Merck.

009

6:09 p.m. – 6:12 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Efficacy and safety of erenumab in episodic migraine patients with 2–4 prior preventive treatment failures: Results from the Phase 3b LIBERTY study

Uwe Reuter; Peter Goadsby, MD, PhD; Michel Lanteri-Minet, MD, Michel Ferrari, MD, PhD; Shihua Wen; Jan Klatt

Objective: To assess the efficacy and safety of erenumab in patients with episodic migraine who have failed 2–4 prior preventive migraine treatments (PMTs). Background: Erenumab is a fully human monoclonal antibody that inhibits the canonical CGRP receptor. Clinical studies have demonstrated the efficacy and safety of erenumab in patients with episodic and chronic migraine. Current oral preventive therapies are associated with low adherence rates due to the lack of efficacy and/or poor tolerability. It is therefore important to assess the safety and efficacy of erenumab in patients who have failed multiple therapies. Design/Methods: LIBERTY (NCT03096834) was a 12-week, double-blind, randomized study. Patients (N=246) were randomized (1:1) to receive erenumab 140mg and placebo. The primary endpoint was the proportion of patients achieving ≥50% reduction in mean monthly migraine days (MMDs) during Weeks 9-12 (Month 3). Secondary endpoints included change from baseline to Month 3 in MMDs and monthly acute migraine-specific medication days (MSMDs) and safety/tolerability. Results: At baseline, proportion of patients who failed 2, 3, and 4 prior PMTs were 38.6%, 37.8%, and 22.8%, respectively. The mean (SD) MMDs and MSMDs were 9.3 (2.64) and 4.6 (2.89), respectively. At week 12, the proportion of patients achieving ≥50% reduction in MMD was higher in those treated with erenumab 140mg vs placebo (30.3% vs 13.7%; OR [95% CI]: 2.73 [1.43, 5.19]; p=0.002). At week 12, there were greater reductions in MMDs and MSMDs with erenumab 140mg vs placebo (mean difference [95% CI] in MMD: −1.61 [−2.70, −0.52]; p=0.004; mean difference (95% CI) in MSMD: −1.73 [−2.46, −1.01]; p<0.001). Safety and tolerability profile of erenumab was comparable to placebo. No patients in the erenumab group discontinued due to adverse events. Conclusions: These results confirm the efficacy and safety of erenumab in this first dedicated study of a difficult to treat population with 2–4 prior preventive migraine treatment failures.

Study Supported By: Novartis Pharma AG, Basel, Switzerland

Disclosures: Dr. Reuter has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen, Co-Lucid, Autonomic Technologies, Novartis, Eli Lilly, Pharm-Allergan and Teva. Dr. Goadsby has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Biopharmaceuticals, Allergan, Amgen, Electrocore, Eli-Lilly, eNeura, Novartis and Teva. Dr. Goadsby has received personal compensation in an editorial capacity for Journal Watch, Up-to-Date, Oxford Univeristy Press, Massachusetts Medical Society and Walters Kluwer. Dr. Goadsby has received compensation for serving on the Board of Directors of Trigemina, Inc. Dr. Goadsby has received research support from Amgen. Dr. Lanteri-Minet has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Astellas, ATI, Grunenthal, Lilly, Medtronic, Novartis, Pfizer, Sanofi and Teva. Dr. Lanteri-Minet has received research support from Medtronic and Novartis. Dr. Ferrari has received research support from the Netherlands Organization for Scientific Research (NWO), the European Community, ZonMw and the Dutch Heart Foundation. Dr. Wen is an employee of Novartis. Dr. Klatt is an employee of Novartis.

P4.466

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

AVXS-101 Gene Replacement Therapy for SMA Type 1: Pivotal Study (STR1VE) Update

John W. Day, MD, PhD; Douglas Feltner, MD; Francis Ogrinc, PhD; Thomas Macek, PhD; Courtney Wells; Lynlee Muehring; James L’Italien, PhD; Jessica Cardenas, PhD; Douglas Sproule, MD; Sukumar Nagendran; Brian Kaspar, PhD; Jerry Mendell, MD, FAAN

Objective: STR1VE is a pivotal phase 3 study (NCT03306277) investigating efficacy and safety of a one-time intravenous infusion of AVXS-101, a potential SMN gene replacement therapy, in a minimum of 15 patients with Spinal Muscular Atrophy Type 1 (SMA1). We report the phase 3 clinical study design and baseline demographics. Background: SMA1 is a neurodegenerative disease leading to respiratory failure and early death. Patients fail to achieve motor milestones, and motor function declines, as measured by CHOP-INTEND. Phase 1 (NCT02122952) data demonstrated that AVXS-101 improved survival and motor function in SMA1 patients. CHOP-INTEND scores increased at 1 and 3 months compared with a decline in a historical cohort. Four patients experienced asymptomatic elevations in serum aminotransferase soon after dosing that were attenuated by prednisolone. Design/Methods: STR1VE is a phase 3, multi-center (16 sites), open-label, single-arm, one-time-dose study in SMA1 patients SMN1 mutations, and 1–2 SMN2 copies). For the first 3 patients, a 4-week dosing interval allows review of safety data and of early signs of efficacy prior to dosing the next patient. The primary outcomes are achievement of independent sitting for 30 seconds at 18 months of age, and survival (avoidance of death or permanent ventilation) at 14 months of age. Results: As of Jan 30, 2018, 3 SMA1 patients with 2 SMN2 copies have been enrolled. Age at enrollment and symptom onset was 2.7 months (1.8–4.3 months) and 1.0 months (0.5–2.0 months), respectively. The mean baseline CHOP-INTEND score was 24.3 (18–34). No patients required ventilatory or nutritional support. Conclusions: The AVXS-101 phase 3 pivotal study investigates the efficacy and safety of a one-time intravenous infusion of AVXS-101 SMNgene replacement in SMA1 patients. Updated patient data with follow-up will be presented.

Study Supported By: AveXis, Inc.

Disclosures: Dr. Day has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Ionis Pharmaceuticals, Roche Pharmaceuticals, Cytokinetics, Pfizer, AveXis, AMO Pharmaceuticals, Sarepta Therapeutics and Santhera Pharmaceuticals. Dr. Day has received (royalty or license fee or contractual rights) payments from Athena Diagnostics. Dr. Day has received research support from Biogen, Ionis Pharmaceuticals, Cytokinetics, Roche Pharmaceuticals, aTyr, AveXis, Bristol Meyers Squibb, Sanofi-Genzyme, AMO Pharmaceuticals and Sarepta Therapeutics.Dr. Feltner is employed by AveXis and has received personal compensation for consulting with Acadia and Embera Neurtherapeutics. Dr. Feltner has received compensation for serving on the Board of Directors of Embera Neurotherapeutics. Dr. Feltner holds stock and/or stock options in AveXis. Dr. Ogrinc is an employee with AveXis, Inc. Dr. Macek is an employee of AveXis, Inc. and has received personal compensation for consulting with the Gerson Lehrmen Group. Dr. Wells is an employee with AveXis, Inc. Dr. Muehring is an employee with AveXis, Inc. Dr L’Italien is an employee with AveXis, Inc. and holds stock/stock options in the company. Dr. Cardenas is employed by AveXis, Inc. and has received stock options for serving on a board of directors for a commercial entity. Dr. Sproule is an employee of AveXis, Inc. and has stock options in the company. Dr. Nagendran is an employee of AveXis, Inc. and has stock options in the company. Dr. Kaspar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Inc. Dr. Kaspar hold stock and/or stock options in AveXis, Inc. Dr. Mendell has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Inc. and Sarepta Therapeutics. Dr. Mendell has received research support from Sarepta Therapeutics Inc. and AveXis, Inc.

P4.467

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Effect of ZX008 (Fenfluramine HCl Oral Solution) on Total Seizures in Dravet Syndrome

Joseph Sullivan; Lieven Lagae; Kelly Knupp, MD; Bradley Galer; Glenn Morrison; Arnold Gammaitoni; Gail Farfel

Objective: To assess the effect of ZX008 (fenfluramine) on total seizure (TS) frequency in patients with Dravet syndrome (DS). Background: DS is a rare, severe, treatment-resistant epileptic encephalopathy. In a Phase 3, randomized, double-blind, placebo-controlled trial, ZX008 significantly reduced monthly convulsive seizure (CS) frequency (defined as tonic-clonic, tonic, atonic, clonic, and focal motor seizures). Here we present secondary analyses of the effect of ZX008 on TS frequency. Design/Methods: Patients (2-18 years old) with a diagnosis of DS in whom CSs were not completely controlled by their current anti-epileptic drug regimen were enrolled. Following a 6-week baseline period, patients were randomized 1:1:1 to placebo, ZX008 0.2 mg/kg/day, or ZX008 0.8 mg/kg/day (maximum dose 30 mg/day) and treated for 14 weeks, including an initial 2-week titration period. The number and type of seizures were recorded daily in an electronic diary by caregivers. Results: A total of 119 patients with DS enrolled in the study and were randomized to treatment (n=40, 0.8 mg/kg/day; n=39, 0.2 mg/kg/day; n=40, placebo). Mean subject age was 9±4.7 years. During baseline, the median monthly TS frequency ranged from 40.7 to 53.9 in the three groups. During the 14-week treatment period, median percent changes in TS frequency were 13.1% in placebo, -34.3% in ZX008 0.2 mg/kg/day (p=0.031), and -70.1% in ZX008 0.8 mg/kg/day (p<0.001). In addition to the effect of ZX008 0.8 mg/kg/day on CS, improvements in myoclonic and absence seizures were also observed. ZX008 was generally well tolerated. Conclusions: ZX008 may represent an important and effective new treatment option for patients with DS, with improvement in several seizure types.

Study Supported By: Zogenix, Inc.

Disclosures: Dr. Sullivan has received personal compensation for consulting and advising activities with Epygenix, Epilepsy Study Consortium and Dravet Syndrome Foundation. Dr. Sullivan has received research support from Zogenix. Dr. Lagae has received personal compensation for consulting and advising activities with LivaNova, Novartis, Ovid, Shire and Zogenix. Dr. Lagae and the KU Leuven University/Antwerp University Hopsital may benefit financially from a royalty agreement that is related to this research if Zogenix is successful in marketing its product, fenfluramine. The terms of this arrangement have been reviewed and approved by the KU Leuven University/Antwerp University Hospital. Dr. Knupp has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Greenwich Biosciences and Dravet Syndrome Foundation. Dr. Knupp has received research support from Zogenix, PERF and West Therapeutics. Dr. Galer is an employee of Zogenix and holds stock in the company. Dr. Morrison is an employee of Zogenix and holds stock in the company. Dr. Gammaitoni is an employee of Zogenix and holds stock in the company. Dr. Farfel is an employee of Zogenix and holds stock in the company.

P4.468

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Transdermal Cannabidiol (CBD) Gel for the Treatment of Focal Epilepsy in Adults

John A. Messenheimer, Jr., MD; Terence O’Brien, MD; Samuel Berkovic, MD, FRACP; Jacqueline French, MD, FAAN; Marcel Bonn-Miller, PhD; Donna Gutterman, PharmD

Objective: Evaluate the safety and efficacy of ZYN002 (transdermal cannabidiol [CBD] gel) as adjunctive therapy for the treatment of adult focal seizures. Background: CBD can reduce seizures in pediatric patients, but data in adults are limited. Design/Methods: STAR 1 was a phase 2A, randomized, double-blind, placebo-controlled study of ZYN002 administered BID for 12 weeks to adults with focal seizures. Patients were initially randomized 1:1:1 to 195 mg or 390 mg CBD daily, or placebo. STAR 2 is the open-label extension study for completers of STAR 1. In STAR 2, all patients started on 390 mg CBD daily. Results: 188 patients were initially randomized into STAR 1. After 12 weeks, the median reduction in focal seizures was 18.4% (195 mg CBD/day; n=63), 14.0% (390 mg CBD/day; n=62), and 8.7% (placebo; n=63). There were no statistically significant differences in efficacy between ZYN002 and placebo. 174 patients completed STAR 1 and 171 patients rolled into STAR 2. Seizure control was evaluated as a function of duration on ZYN002, regardless of initial randomization group or dose. Longer exposure to ZYN002 resulted in greater improvements in seizure frequency, with median percent change in seizures from -16.3% at 3 months (n=170), to -27.3% at 6 months (n=148), -50.2% at 9 months (n=98), and -58.0% at 12 months (n=70). ZYN002 was well tolerated, with excellent skin tolerability. The most common adverse events were upper respiratory tract infection (viral and bacterial; 16%), headache (11%), fatigue (7%), and laceration (5%). Conclusions: While change in seizure frequency was not significantly different between active and placebo during STAR 1, continued treatment with ZYN002 in STAR 2 appeared to result in improvements in seizure control, with clinically meaningful reductions observed by 6 months of treatment and maintained through 12 months. ZYN002 (administered BID) was well tolerated, with excellent patient compliance and acceptance.

Study Supported By: Zynerba Pharmaceuticals, Inc.

Disclosures: Dr. Messenheimer has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Zynerba Pharmaceuticals. Dr. O'Brien has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with SciGen, Eisai and UCB Pharma. Dr. O'Brien's institution has received funding from Eisai, Janssen-Cilag, Sanofi-Genzyme, SciGen, Zynerba Pharmaceuticals and UCB Pharma. Dr. Berkovic has received personal compensation for serving on scientific advisory boards for UCB and Eisai. Dr. Berkovic has received research support for contracted drug trials from UCB Australia Pty Ltd, SK Life Science Inc, Upsher–Smith Laboratories, Zynerba Pharmaceuticals, Eisai and Marinus. Dr. Berkovic has received research support from UCB, Eisai and SciGen. Dr. French has received research support from Acorda, Alexza, Eisai Medical Research, LCGH, Lundbeck, Pfizer, SK Life Sciences, Sunovion, Takeda and UCB. Dr. Bonn-Miller is an employee of Zynerba Pharmaceuticals. Dr. Gutterman is an employee of Zynerba Pharmaceuticals.

P4.469

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

ZX008 (Fenfluramine HCL Oral Solution) in Dravet Syndrome: Effect on Convulsive Seizure Frequency in Subjects Who Failed Treatment with Stiripentol Prior to Study 1

Elaine Wirrell, MD, FAAN; Rima Nabbout; Linda Laux, MD; Joseph Sullivan; An-Sofie Schoonjans; Gail Farfel; Bradley Galer; Glenn Morrison; Arun Mistry; Arnold Gammaitoni

Objective: To assess the effect of ZX008 on frequency of convulsive seizures (FCS) in a subset of Dravet syndrome (DS) subjects in a Phase 3 clinical trial (Study 1) who had previously been treated with stiripentol. For this analysis, subjects who had discontinued stiripentol prior to study entry were defined as failures. Background: Stiripentol is approved in Europe, Australia, Canada, and Japan (and available for compassionate use in the USA) for adjunctive treatment of patients with DS. Here we present a subgroup analysis of the effect of ZX008 on FCS in subjects who discontinued stiripentol prior to entry in Study 1 (N=119). Design/Methods: Following a 6-week baseline period, subjects were randomized 1:1:1 to placebo (n=16), ZX008 0.2 mg/kg/day (n=20), or ZX008 0.8 mg/kg/day, maximum dose 30 mg/day (n=22) and treated for 14 weeks, including an initial 2-week titration period. Number and type of seizures were recorded daily in an electronic diary. Results: A total of 58 subjects met the criteria for this analysis with a mean age 9.7 years (range, 2-18). ZX008 0.8 mg/kg/day showed a 60.8% reduction in mean monthly FCS vs placebo (p=0.002). Seventy-three percent of subjects in the ZX008 0.8 mg/kg/day group achieved& ge;50% reduction in FCS (p=0.006) and 50% achieved &ge;75% reduction in FCS (p=0.036). Longest median seizure-free intervals were 24.5 days (0.8 mg/kg/day, p=0.003), 18 days (0.2 mg/kg/day, p=0.012), and 9 days (placebo). Compared with placebo, ZX008 0.8 mg/kg/day-treated subjects were more likely to be rated much or very much improved by parents/caregivers (41% vs 6%, p=0.012) and investigators (64% vs 6%, p&lt;0.001). ZX008 was generally well tolerated. Conclusions: ZX008 provided robust improvement in FCS in subjects who had previously used stiripentol, the only approved treatment for seizures in DS. ZX008 may represent an effective new treatment option for these patients with DS.

Study Supported By: Zogenix

Disclosures: Dr. Wirrell has received personal compensation for consulting and advising activities with Biomarin, Sunovion and Dravet Syndrome Foundation. Dr. Wirrell has received research support from Zogenix and GW Pharma. Dr. Nabbout has received personal compensation for consulting and lecture activities with Zogenix, Advicennes, UCB, Biomarin, Eisai, GW Pharma and Novartis. Dr. Laux has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Dravet Syndrome Foundation. Dr. Laux has received research support from Zogenix and Greenwich Biosciences. Dr. Sullivan has received personal compensation for consulting and advising activities with Epygenix, Epilepsy Study Consortium and Dravet Syndrome Foundation. Dr. Sullivan has received research support from Zogenix. Dr. Schoonjans has received consulting and advising fees from Brabant and Zogenix. Dr. Farfel is an employee of Zogenix and holds stock in the company. Dr. Galer is an employee of Zogenix and holds stock in the company. Dr. Morrison is an employee of Zogenix and holds stock in the company. Dr. Mistry is an employee of Zogenix and holds stock in the company. Dr. Gammaitoni is an employee of Zogenix and holds stock in the company.

P4.470

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Eptinezumab Achieved Meaningful Reductions in Migraine Activity As Early As Day 1 and Were Sustained Through Week 12: Results From PROMISE-2 (Prevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-2) Phase 3 Trial in Chronic Migraine

David B. Kudrow, MD; Merle Diamond; Lora McGill, MD, FAAN; Roger Cady; Suman Bhattacharya; David Biondi, DO, FAAN; Joe Hirman; Jeff Smith

Objective: Evaluate effects of eptinezumab on migraine activity from Day 1 post intravenous (iv) infusion through Weeks 4 and 12 in subjects with chronic migraine. Background: Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology. Eptinezumab , a humanized, anti-CGRP monoclonal antibody with 100% bioavailability following iv administration, selectively and potently inhibits CGRP. Design/Methods: Adults with CM (ICDH-3 beta) were randomized (1:1:1) to eptinezumab 100 mg, 300 mg, or placebo. Infusions were administered on Day 0 and at Week 12. The primary endpoint was change from baseline in frequency of monthly migraine days (MMD) over Weeks 1-12. A key secondary endpoint was percentage of subjects with a migraine on Day 1 postinfusion. Another secondary endpoint was reduction from baseline in MMD over each month. Results: Efficacy analysis included 1072 subjects. Mean baseline MMD in 100-mg, 300-mg, and placebo groups were 16.1, 16.1, and 16.2, respectively. Mean reductions from baseline in MMD over Weeks 1-12 were -7.7 (p<0.0001) and -8.2 (p<0.0001) vs -5.6, respectively. Similar mean reductions from baseline in MMD were observed over monthly intervals: Weeks 1-4, -7.6 and -8.3 vs -5.3; Weeks 5-8, -8.1 and -8.5 vs -6.1; and Weeks 9-12, -7.7 and -8.2 vs -6.0. The average percent of subjects with a migraine on any given day during the baseline period in the 100-mg, 300-mg, and placebo groups was 57.5%, 57.4%, and 58.0%, respectively. The percent of subjects with a migraine on Day 1 postinfusion was 28.6% (-50.3% [p=0.0001]) and 27.8% (-51.6% [p<0.0001]) with eptinezumab 100 and 300 mg, respectively, vs 42.3% (-27.1%) with placebo. The safety profile was consistent with previous clinical trials of eptinezumab. Conclusions: A single infusion of eptinezumab significantly reduced MMD for 3 months in subjects with CM. The percentage of subjects with a migraine on Day 1 was reduced by approximately 50% following eptinezumab infusion.

Study Supported By: Alder BioPharmaceuticals, Inc., Bothell, WA, USA

Disclosures: Dr. Kudrow has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen, Alder and Ely Lilly. Dr. Kudrow has received research support from Amgen, Alder, Ely Lilly, Allergan, Biohaven, Colucid, Genentech-Roche and Teva. Dr. Diamond has nothing to disclose. Dr. McGill has nothing to disclose. Dr. Cady is a full-time employee with Alder Biopharmaceuticals. Dr. Bhattacharya is a full-time employee with Alder Biopharmaceuticals. Dr. Biondi is a full-time employee with Alder Biopharmaceuticals. Dr. Hirman has received personal compensation for consulting with Alder Biopharmaceuticals. Dr. Smith is a full-time employee of Alder Biophamaceuticals.

P4.471

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Eptinezumab Reduced Migraine Frequency and Triptan/Ergotamine Use Over Weeks 1-12, and Improved HIT-6 Scores at Months One and Three: Results From the Phase 3 PROMISE-2 Trial in Chronic Migraine

Stephen D. Silberstein, MD, FAAN; Egilius Spierings, MD, PhD; Gary Berman, MD; David Biondi, DO, FAAN; Jeff Smith; Suman Bhattacharya; Roger Cady

Objective: Evaluate the effects of eptinezumab on migraine frequency and triptan/ergotamine use over Weeks 1-12, and on Headache Impact Test-6 (HIT-6) scores over Weeks 1-4 and Weeks 9-12, in subjects with chronic migraine (CM). Background: Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology. Eptinezumab a humanized, anti-CGRP monoclonal antibody with 100% bioavailability following intravenous administration, selectively and potently inhibits CGRP. Design/Methods: Adults with CM (ICHD-3 beta) were randomized (1:1:1) to eptinezumab 100 mg, 300 mg, or placebo. Infusion was administered on Day 0 and at Week 12. The primary endpoint was mean change from baseline in monthly migraine days (MMD) over Weeks 1-12. Secondary endpoints included change in days of triptan/ergotamine use over Weeks 1-12 and HIT-6 score changes from baseline. Subjects completed HIT-6 questionnaires at baseline and at Weeks 4 and 12. Results: Efficacy analysis included 1072 subjects. Mean baseline MMD in the 100- mg, 300-mg, and placebo groups were 16.1, 16.1, and 16.2, respectively. Mean reductions from baseline in MMD over Weeks 1-12 were -7.7 (p&lt;0.0001) and -8.2 (p&lt;0.0001) for eptinezumab 100 mg and 300 mg, respectively, vs -5.6 for placebo. Mean triptan/ergotamine medication days/month at baseline were 6.6, 6.7, and 6.2 in the 100-mg, 300-mg, and placebo groups, respectively. Over Weeks 1-12, mean triptan/ergotamine medication days/month were 3.3 (-3.3 [p&lt;0.0001*]) and 3.2 (-3.5 [p&lt;0.0001]) vs 4.3 (-1.9), respectively. Mean HIT-6 baseline scores in the 100-mg, 300-mg, and placebo groups were 65.0, 65.1, and 64.8, respectively. Mean HIT-6 score improvements from baseline were -7.0and -8.6vs -4.7 over Weeks 1-4, and -6.2 (p=0.0011*) and -7.4 (p&lt;0.0001) vs -4.5 over Weeks 9-12. Conclusions: A single infusion of eptinezumab in subjects with CM significantly reduced mean MMD over 3 months. This benefit was associated with overall reductions of approximately 50% in triptan/ergotamine use and meaningful improvements in HIT-6 scores. *Unadjusted.

Study Supported By: Alder BioPharmaceuticals, Inc., Bothell, WA, USA.

Disclosures: Dr. Silberstein has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder Biopharmaceuticals, Allergan, Inc., Amgen, Avanir Pharmaceuticals, Inc., Curelator, Inc., Dr. Reddy’s Laboratories, eNeura Inc., electroCore Medical, LLC, Lilly USA, LLC, Medscape, LLC., NINDS, Supernus Pharmaceuticals, Inc., Teva Pharmaceuticals, Theranica and Trigemina, Inc. Dr. Silberstein's employer receives research support from Allergan, Inc., Amgen, Cumberland Pharmaceuticals, Inc., ElectroCore Medical, LLC, Labrys Biologics, Eli Lilly and Company and Merz.Dr. Spierings has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder and Ely Lilly. Dr. Spierings has received research support from Alder, Amgen, Teva, Allergan and Pfizer. Dr. Berman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder and AmGen. Dr. Biondi is a full-time employee of Alder Biopharmaceuticals. Dr. Smith is a full-time employee of Alder Biopharmaceuticals. Dr. Bhattacharya is a full-time employee of Alder Biopharmaceuticals. Dr. Cady is a full-time employee of Alder Biopharmaceuticals.

P4.472

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Clinical Development of VX15/2503 Anti-Semaphorin 4D Antibody as a Potential Treatment for Huntington’s Disease

Elizabeth Evans, PhD; Terry Fisher, PhD; Maurce Zauderer; John Leonard; Danielle Fisher; Leslie Balch; Alan Howell; Crystal Mallow; Ernest Smith, PhD; Andrew Feigin, MD

Objective: Evaluation of VX15/2503, a first-in-class antibody to Semaphorin 4D (SEMA4D), in a randomized double-blind, placebo-controlled phase 2 clinical trial (SIGNAL) enrolling late prodromal and early manifest HD subjects. Background: SEMA4D signaling through its receptor triggers activation of inflammatory glial cells, inhibits migration and differentiation of oligodendrocyte precursor cells, and disrupts endothelial tight junctions that maintain the blood-brain barrier (BBB). Chronic inflammation, neuronal degeneration, and disruption of the BBB are believed to play important roles in neuroinflammatory and neurodegenerative diseases. Antibody neutralization of SEMA4D ameliorates neurodegenerative processes in several preclinical models, including HD transgenic mice. Design/Methods: The SIGNAL trial evaluates the safety, tolerability and efficacy of VX15/2503. Endpoints include clinical features of HD and imaging, including volumetric MRI, considered an early biomarker with prognostic significance for HD, and FDG-PET measures of glucose metabolism in prospectively defined brain regions of interest (ROI). Results: The recently completed first cohort in this first study of a biologic administered to HD subjects (n=36) demonstrated that rapid recruitment is feasible. No concerning safety signals were identified following up to 12 monthly IV administrations and a three-month safety follow-up. VX15/2503 treatment trended toward stabilization of disease-related reduction in MRI volume and favored VX15 over placebo in 24/31 ROI, especially among frontal and adjacent parietal lobes. FDG-PET imaging also favored VX15 in all ROI, with median increase in FDG uptake from baseline of 8.6% (range: 0.5-20.4%) compared to placebo control and p-value <0.1 in 19/31 ROI, including 12/14 ROI within the frontal and parietal regions. Conclusions: Data from Cohort A suggests that treatment with VX15/2503 was well tolerated and appeared to prevent loss of brain volume and restore metabolic activity. These results informed the design of a larger cohort of subjects in this continuing study, in which additional clinical features of HD, including cognition and motor assessments, will be evaluated.

Study Supported By:

Disclosures: Dr. Evans is a full-time employee of Vaccinex and holds stock options in the company. Dr. Fisher is a full-time employee of Vaccinex. Dr. Zauderer is a full-time employee of Vaccinex. Dr. Leonard is a full-time employee of Vaccinex and holds stock and/or stock options in the company. Dr. Fisher is a full-time employee of Vaccinex. Dr. Balch is a full-time employee of Vaccinex. Dr. Howell is a full-time employee of Vaccinex. Dr. Mallow is a full-time employee of Vaccinex. Dr. Smith is a full-time employee of Vaccinex and holds stock in the company. Dr. Feigin has received personal compensation for activities with Oxford Medica as an advisory board member. Dr. Feigin has received research support from Vaccinex, Teva and Voyager Therapeutics.

P4.473

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

A Randomized Trial of Deferiprone for Pantothenate Kinase-Associated Neurodegeneration (on behalf of the TIRCON Group)

Thomas H. Klopstock, MD

Objective: To investigate whether treatment with the iron-chelating drug deferiprone (DFP) has benefit in patients with pantothenate kinase-associated neurodegeneration (PKAN), the most common form of neurodegeneration with brain iron accumulation (NBIA). Background: PKAN is a rare genetic disorder characterized by progressive dystonia and iron accumulation in the globus pallidus. Reduction of brain iron might slow the progression of symptoms. The iron chelator DFP can cross the blood-brain barrier and remove labile iron from neuronal cells. Design/Methods: Eighty-nine PKAN patients were randomized in a 2:1 ratio to receive either DFP or matching placebo for 18 months. Efficacy was assessed using the Barry-Albright Dystonia (BAD) scale, the Patient Global Impression of Improvement (PGI-I), and numerous tests of functional abilities and activities of daily living. Brain iron was measured at baseline and month 18 using MRI R2*. Results: After 18 months, MRI showed a sharp drop in brain iron the DFP group while the placebo group had virtually no change, for a treatment group difference of -35.6 Hz (p < 0.0001). In patients with atypical PKAN, a slower-progressing form of the disease, DFP-treated patients worsened by 2.19 points less than placebo patients on the total BAD score (p=0.0187). In the intention-to-treat analysis of all patients, however, this group difference did not reach significance with DFP-treated patients worsening by 1.51 points less than the placebo group (p=0.0761). No significant differences were seen on other efficacy measures, but there was a pattern suggesting an effect for deferiprone on the majority of measures. With regard to safety, deferiprone was well tolerated. Conclusions: Patients with PKAN who received DFP for 18 months showed a significant decrease in brain iron and a trend suggesting slower progression of symptoms as compared to patients who received placebo.

Study Supported By: European Commission, the US FDA, and ApoPharma Inc., Canada.

Disclosures: Dr. Klopstock has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Santhera. Dr. Klopstock has received research support from Santhera, GenSight, Actelion, Genzyme and ApoPharma.

P4.474

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Non-Invasive Peripheral Nerve Stimulation for Symptomatic Relief of Hand Tremor in Essential Tremor

Rajesh Pahwa, MD, FAAN; Monique Giroux, MD; Jill Ostrem, MD; Rohit Dhall, MD; Pinky Agarwal, MD, FAAN; Ryder Gwinn, MD; Dhira Khosla, DO; Kelly Lyons, PhD; Paula Chidester, MS; Erika Ross, PhD; Scott Delp, PhD

Objective: We evaluated the safety and efficacy of a non-invasive neuromodulation therapy for hand tremors in essential tremor (ET) using a custom stimulation pattern tuned to interrupt each patient’s tremulous signal in both acute and at-home settings. Background: Although the precise mechanisms of ET are uncertain, it is thought to be caused by tremulous activity within a central tremor network. There is myriad clinical evidence supporting invasive neuromodulation of deep brain structures within this network in ET patients. Few studies have investigated the effect of non-invasive neuromodulation of the connecting peripheral nerve inputs to this network in tremor. Design/Methods: In the acute study, 77 subjects were randomized to receive either peripheral nerve treatment or sham stimulation of the tremor dominant hand. Tremor was evaluated before and after a single stimulation session. For the chronic study, 61 subjects were randomized to treatment, sham, or standard-of-care. Subjects underwent a minimum of two sessions each day throughout the study. Results: The acute study demonstrated that the therapy was safe and produced significant improvements compared to sham in the physician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) dominant upper limb scores (p=0.017), and in patient-rated Bain&amp; Findley activities of daily living (ADL) scores (p = 0.001). No significant adverse events were reported, 3% of subjects experienced mild adverse events (skin redness, irritation) that spontaneously resolved without intervention. In the chronic study, baseline tremor characteristics, including tremor frequency (5.3 Hz +/-; 1.1 Hz), were identified in the kinematic data as well as tremor characteristics and response over the course of the study. Conclusions: These randomized controlled studies suggest that non-invasive peripheral neuromodulation may offer meaningful symptomatic relief from hand tremor in ET with a favorable side effect profile compared to other available therapies, and that at-home monitoring may provide key insights into evaluating and treating tremor.

Study Supported By: Cala Health, Inc.

Disclosures: Dr. Pahwa has received consulting fees from Abbvie, ACADIA, Acorda, Adamas, Cynapses, Global Kinetics, Lundbeck, Neurocrine, Pfizer, Sage, Sunovion, Teva Neuroscience and US World Meds. Dr. Pahwa has received personal compensation in an editorial capacity as the Co-Editor-In-Chief of the International Journal of Neuroscience. Dr. Pahwa has received research support from Abbvie, Adamas, Avid, Biotie, Boston Scientific, Cala Health, Civitas, Cynapses, Kyowa, National Parkinson Foundation, NIH/NINDS, Parkinson Study Group and Pfizer.Dr. Giroux has received personal compensation as a board member for Cala Health, Inc. Dr. Giroux has received research support from Cala Health, Inc. Dr. Ostrem has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Neurocrine and Adamas. Dr. Dhall has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Best Doctors. Dr. Dhall has received research support from Axovant, Biotie pharmaceuticals (now part of Acorda) and Impax Pharmaceuticals. Dr. Agarwal has received personal compensation for activities compensation for consulting, serving on a Scientific board, speaking, or other activities with US world meds, Teva, Acadia, Lundbeck and Impax. Dr. Agarwal has received research support from Pfizer, Northwestern University, CHDI Foundation, Merck & Co, US WorldMeds, Dystonia Coalition, Astellas, Adamas, Teva Pharmaceuticals, University of Rochester, Huntington Study Group, Partners Healthcare, Chiltern International, Omeros Cor and Cala Health. Dr. Gwinn has received personal compensation for consulting with Bioneuronics. Dr. Khosla has received personal compensation for consulting, serving on a scientific advisory board, or other activities with Cala Health, Inc. Dr Khosla has received research support from Cala Health, Inc. Dr. Lyons is the President of the International Essential Tremor Foundation and has received compensation as a consultant for Sage. Dr. Lyons has received personal compensation in an editorial capacity as the Co-Editor-In-Chief of the International Journal of Neuroscience. Dr. Chidester is an employee of Cala Health, Inc. Dr. Ross is an employee of Cala Health, Inc. and holds stock and/or stock options in the company. Dr. Delp receives personal compensation for consulting, scientific advising and board member activities with Cala Health, Inc., Circuit Therapeutics, Inc. and Zebra Medical Technologies, Inc.

P4.475

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Natalizumab extended interval dosing (EID) is associated with a significant reduction in progressive multifocal leukoencephalopathy (PML) risk compared with standard interval dosing (SID) in the TOUCH^® Prescribing Program

Lana Zhovtis Ryerson, MD; John Foley, MD; Ih Chang; Ilya Kister, MD, FAAN; Gary Cutter, PhD; Ryan Metzger, PhD; Judith Goldberg; Xiaochun Li; Evan Riddle, PhD; Karen Smirnakis; Bei Yu; Zheng Ren; Chistophe Hotermans, MD, PhD; Pei-Ran Ho; Nolan Campbell

Objective: To determine whether natalizumab EID is associated with reduced PML risk compared with SID. Background: Natalizumab, approved for 300 mg intravenous every-4-weeks dosing, is associated with PML risk. Prior studies have been inconclusive regarding EID’s impact on PML risk. The US REMS program (TOUCH) offers the largest data source that can inform on PML risk in patients on EID. Design/Methods: Investigators developed SID and EID definitions and finalized the statistical analysis plan while blinded to PML events. Average dosing intervals (ADIs) were ≥3 to 5 to ≤12 weeks for EID. The primary analysis assessed ADI in the last 18 months of infusion history. The secondary analysis identified any prolonged period of EID at any time in the infusion history. The tertiary analysis assessed ADI over the full infusion history. Only anti-JC virus antibody positive (JCV Ab+) patients with dosing intervals ≥3 to ≤12 weeks were included. EID and SID PML hazard ratios (HRs) were compared using adjusted Cox regression models and Kaplan-Meier estimates. Results: Analyses included 13,132 SID and 1988 EID patients (primary), 15,424 SID and 3331 EID patients (secondary), and 23,168 SID and 815 EID patients (tertiary). In primary analyses, ADI (days) was 30 for SID and 37 for EID; median exposure (months) was 44 for SID and 59 for EID. Most EID patients had >2 years SID treatment prior to EID. The PML HR (95% confidence interval) was 0.06 (0.01-0.22; P<0.001) for primary and 0.12 (0.05-0.29; P<0.001) for secondary analyses (both in favor of EID); no EID PML cases were observed in tertiary analyses (Kaplan-Meier log-rank test P=0.02). Conclusions: In JCV Ab+ patients, natalizumab EID is associated with a clinically and statistically significant reduction in PML risk as compared with SID. As TOUCH does not collect effectiveness data, further studies are needed.

Study Supported By: Biogen

Disclosures: Dr. Zhovtis Ryerson has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Teva and Genetech. Dr. Zhovtis Ryerson has received research support from Biogen.Dr. Foley has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Genentech, Genzyme and Teva. Dr. Foley has received research support from Biogen, Alkermes, Mallinckrodt, Novartis, Genzyme, Genentech, Teva and Abreos. Dr. Chang is an employee of Biogen and has received compensation for serving on the board of directors at Biogen. Dr. Chang also holds stock and/or stock options in Biogen. Dr. Kister has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen and Genetech. Dr. Kister has received research support from Genzyme. Dr. Cutter has received personal compensation for activities compensation for serving on data and safety monitoring boards with AMO Pharmaceuticals, Apotek, Horizon Pharmaceuticals, Merck, Merck/Pfizer, Modigenetech/Prolor, Neurim, Opko Biologics, Reata Pharmaceuticals, Receptos/Celgene, Sanofi, Teva Pharmaceuticals, NHLBI (Protocol Review Committee), and NICHD (OPRU oversight committee); has received compensation for consulting or advisory boards from Argenix, Atara Biotherapeutics, Bioeq GmBH, Consortium of MS Centers (grant), Genentech, Genzyme, Innate Therapeutics, Klein-Buendel, MedDay, Medimmune, Novartis, Opexa Therapeutics, Roche, Savara, Somahlution, Teva Pharmaceuticals, TG Therapeutics, and Transparency Life Sciences; and is president of Pythagoras, a private consulting company. Dr. Metzger has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen. Dr. Metzger holds stock and/or stock options in Biogen, which sponsored research in which Dr. Metzger was involved as an investigator. Dr. Goldberg has nothing to disclose. Dr. Li has nothing to disclose. Dr. Riddle is a Biogen employee and holds stock in Biogen. Dr. Smirnakis is an employee of Biogen and holds stock and/or stock options in Biogen. Dr. Yu is an employee of Biogen. Dr. Ren is an employee of Biogen and holds stock and/or stock options in Biogen. Dr. Hotermans is an employee of Biogen and holds stock and/or stock options in Biogen. Dr. Ho is an employee of Biogen. Dr. Campbell is an employee of Biogen and holds stock and/or stock options in Biogen.

P4.476 – Withdrawn

P4.477

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

Autologous Haematopoietic Stem Cell Transplantation in Treatment Naïve Patients with ‘Aggressive’ Multiple Sclerosis

Joyutpal Das, MBBS; John Snowden; Mark Freedman, MD, FAAN; Sona Mistry; Simon Bell, MB, ChB, MRCP; Azza Ismail, PhD, MBBS, MRCP; Helen Jessop; Marjorie Bowman; Ricardo Sarccardi; Chiara Innocenti; Harold Atkins; Joachim Burman; Basil Sharrack, MD, PhD, FAAN

Objective: To assess the safety and efficacy of autologous haematopoietic stem cell transplantation (AHSCT) in treatment naïve patients with ‘aggressive’ multiple sclerosis (MS). Background: AHSCT is a very effective treatment in patients with highly active relapsing remitting MS who failed to respond to standard disease modifying therapies (DMTs). International guidelines advocate its use in treatment naïve patients with ‘aggressive’ MS (1). Design/Methods: A total of 19 patients: 7 from Sheffield (UK), 7 from Uppsala (Sweden), 4 from Ottawa (Canada) and 1 from Florence(Italy) with ‘aggressive’ MS received AHSCT between May 2004 and May 2017. None received standard DMTs before AHSCT. BEAM (carmustine, etoposide, cytarabine, melphalan) with antithymocyte globulin (ATG), cyclophosphamide with ATG or combination of cyclophosphamide, ATG and busulphan were used as conditioning regimens. Results: Median age at diagnosis was 33 (21–52) years. Median time between symptom onset and AHSCT was 9 (2–58) months. Median pre-treatment Expanded Disability Status Scale (EDSS) score was 6.5 (1.5–9.5). Median follow up was 30 (6–118) months. Median EDSS score at the last follow up was 2.0 (0–6.5). Median improvement of EDSS scores was 2.0 (0–8) (p<0.05, Wilcoxon signed-rank test). None had any clinical relapse following AHSCT. Three patients had new T2 lesions with or without gadolinium enhancement at the first six month follow up MRI, but no further new or enhancing lesions were observed in any subsequent scans. Routine toxicities were observed with no treatment related mortality. Conclusions: AHSCT was safe and highly effective in inducing rapid and sustain remission in this cohort and was associated with a significant improvement of their level of disability. AHSCT should be considered as first line therapy in patients with ‘aggressive’ MS. 1. Snowden et al. Haematopoietic SCT in severe autoimmune diseases: updated guidelines of European Group for Blood and Marrow Transplantation. Bone Marrow Transplantation 2012Jun;47(6):770-90

Study Supported By:

Disclosures: Dr. Das has nothing to disclose. Dr. Snowden has nothing to disclose. Dr. Mistry has nothing to disclose. Dr. Jessop has nothing to disclose. Dr. Bell has nothing to disclose. Dr. Sharrack has nothing to disclose.

P4.478

Poster Session IV, 11:30 a.m. – 7:00 p.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

B Cell Targeted Treatment in Myasthenia Gravis (BeatMG) - A Phase 2 Trial of Rituximab in Myasthenia Gravis: Topline Results

Richard J. Nowak, MD; Christopher Coffey, PhD; Jonathan Goldstein, MD; Mazen Dimachkie, MD, FAAN; Michael Benatar, MBChB, DPhil, FAAN; Safawa Huq; Brenda Pearson; Jon Yankey; Liz Uribe; Laura Herbelin; Kevin O’Connor; Robin Conwit, MD, FAAN; John Kissel, MD, FAAN; David Hafler, MD, FAAN; Merit Cudkowicz, MD, MSc; Richard Barohn, MD, FAAN

Objective: The specific primary objective of the BeatMG study is to determine whether rituximab is a safe and beneficial therapeutic for myasthenia gravis (MG) that warrants further study in an efficacy trial. Background: MG is an antibody-mediated autoimmune disorder characterized by fatigable muscle weakness. Despite available therapies, some patients continue to have uncontrolled disease or intolerable adverse effects. Autoreactive B cells appear to play an important role in the immunopathogenesis of MG and would seem appropriate for targeted drug therapy investigation. Additionally, encouraging preliminary findings with rituximab provided the rationale for this trial. Design/Methods: We conducted a randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial utilizing a futility analysis for the primary outcome. Participants 21-90 years of age, with confirmed acetylcholine receptor (AChR) antibody positive generalized MG (Myasthenia Gravis Foundation of America Class II-IV) were eligible for enrollment if they were on ≥15 mg of prednisone per day. Participants were randomized 1:1 to receive a two-cycle rituximab regimen (375 mg/m2 IV weekly x 4 weeks, repeated at Week 24) versus matching placebo, and included additional strata based on baseline immunotherapy regimen. The study duration was 52 weeks, and enrolled a total of 52 participants. A forced steroid taper began at Week 8, and was guided by predefined criteria. The primary outcome was a measure of steroid sparing effect, defined as the proportion of participants achieving a ≥75% reduction in mean daily prednisone dose in the 4 weeks prior to week 52 and with clinical improvement or no significant worsening. Safety evaluations included adverse events, vital signs, and laboratory assessments. Secondary outcomes determined whether there was a trend toward clinical benefit as defined by an improvement in MG-specific clinical assessments: Myasthenia Gravis Composite (MGC) and Quantitative Myasthenia Gravis (QMG) scores, among others. Results: Final results from the study will be presented. Conclusions: Conclusions to be discussed.

Study Supported By: The study was supported by grant U01NS084495 from the National Institute of Neurological Disorders and Stroke (NINDS) with drug/placebo provided by Genentech through an investigator-initiated trial agreement.

Disclosures: Dr. Nowak has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals, Ra Pharma and Grifols. Dr. Nowak has received research support from the NIH (NINDS and NIADS), Alexion Pharmaceuticals, Genentech, Grifols, RA Pharma and the Myasthenia Gravis Foundation of America.Dr. Coffey has nothing to disclose. Dr. Goldstein has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion. Dr. Dimachkie has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alnylam, Baxalta, Catalyst, CSL-Behring, Mallinckrodt, Novartis, NuFactor and Terumo. Dr. Dimachkie has received research support from Alexion, Biomarin, Catalyst, CSL-Behring, FDA/OPD, GSK, Grifols, MDA, NIH, Novartis, Orphazyme and TMA. Dr. Benatar has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Eli Lilly. Dr. Benatar has received personal compensation in an editorial capacity with Journal Watch Neurology. Dr. Huq has nothing to disclose. Dr. Pearson has nothing to disclose. Dr. Yankey has nothing to disclose. Dr. Uribe has nothing to disclose. Dr. Herbelin has received personal compensation for consulting activities with RA Pharma. Dr. O’Connor has received personal compensation for educational and consulting activities with Genetech and Editas Medicine. Dr. O’Connor has received research support from RA Pharma. Dr. Conwit has nothing to disclose. Dr. Kissel has received research support from AveXis, Novartis, Cytokinetics, Alexion Pharmaceuticals, Genzyme, CSL Behring, Accelerant and aTyr Pharmaceuticals. Dr. Hafler has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genentech, Bristol Myers Squibb, Medimmune/AstraZeneca, Mylan Pharmaceuticals and Proclara Bioscience. Dr. Hafler has received research support from Bristol Myers Squibb and Genentech. Dr. Cudkowicz has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, Lilly, Astra Zenica, Biohaven, Mitsubishi, Denali, Mt Pharma and Jama Neurology. Dr. Barohn has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with NuFactor, Novartis, Option Care and PlatformQ Health Education. Dr. Barohn has received research support from NIH, FDA/OOPD, NINDS, Novartis, Sanofi/Genzyme, Biomarin, IONIS, Teva, Cytokinetics, Eli Lilly, PCORI, ALSA and PTC.

Clinical Trials Plenary Session

Tuesday, April 24, 2018, 9:15 a.m. – 11:30 a.m.

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

A double-blind placebo-controlled study to evaluate the safety and efficacy of FcRn-antagonist ARGX-113 (efgartigimod) in generalized myasthenia gravis

James F. Howard, Jr., MD, FAAN; Vera Bril, MD; Renato Mantegazza, MD; Andrzef Szczudlik, MD; Said Beydoun, MD, FAAN; Francisco Javier Rodriguez De Rivera Garrido, PhD, MBBS; Mariarosa Rottoli; Fredrik Piehl, MD, PhD; Philip Van Damme; Tuan Vu; Peter Ulrichts; Katrien Verschueren; Antonio Guglietta; Hans de Haard; Nicolas Leupin; Jan Verschuuren, MD, PhD

Objective: To evaluate the safety and efficacy of ARGX-113 (efgartigimod) for the treatment of generalized MG. Background: Myasthenia gravis (MG) is an autoimmune disease driven by IgG autoantibodies targeting the neuromuscular junction hence leading to muscle weakness. ARGX-113 is an Fc fragment antagonizing the IgG salvage receptor FcRn thereby accelerating the degradation of IgGs and reducing their serum levels. This effect may be beneficial in IgG-driven autoimmune diseases such as MG. Design/Methods: A phase 2 randomized, double-blind, placebo-controlled, multicenter study was conducted in 24 patients with generalized MG (gMG). Primary objective of the study was to evaluate the safety and tolerability of ARGX-113 and secondary objectives included an efficacy analysis using four established clinical scales (MG-ADL, QMG, MGC and MG-QoL-15r). Adult anti-AChR+ gMG patients with MG-ADL ≥ 5 were enrolled. Patients were randomized 1:1 to receive four once-weekly infusions of 10 mg/kg ARGX-113 or placebo and were monitored 8 additional weeks after last treatment. Results: ARGX-113 was well tolerated in all patients, with most adverse events characterized as mild and deemed unrelated to the study drug. No serious or severe adverse events were reported. Treatment with ARGX-113 resulted in rapid and strong clinical improvement over placebo lasting for the entire duration of the study as measured by all four efficacy scales (MG-ADL, QMG, MGC and MG-QoL-15r). More specifically, 75% of patients treated with ARGX-113 had a clinically meaningful improvement in MG-ADL scores (≥2-point reduction from baseline) for a period of at least 6 consecutive weeks versus 25% of placebo patients (p = 0.0391). All patients in the treatment arm showed a rapid and deep reduction of their total IgG levels and disease improvement correlated with reduction in pathogenic IgG levels. Conclusions: These results validate ARGX-113 as a potential novel therapeutic option for gMG patients and warrant further clinical evaluation.

Study Supported By: Argenx BVBA

Disclosures: Dr. Howard Jr. has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alexion Pharmaceuticals. Dr. Howard Jr. holds stock and/or stock options in Pfizer, Johnson & Johnson and General Electric. Dr. Howard Jr. has received research support from Alexion Pharmaceuticals, Ra Pharmaceuticals and Argenx BVBA. Dr. Bril has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with CSL, Grifols, Bionevia, UCB, Octapharma, Pfizer and Shire. Dr. Bril has received research support from CSL, Grifols, UCB, Bionevia, Shire and Octapharma. Dr. Mantegazza has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BioMarin, Alexion Pharmaceuticals and Argenx BVBA. Dr. Mantegazza has received research support from Sanofi-Genzyme, Teva, Bayer and BioMarin. Dr. Szczudlik has nothing to disclose. Dr. Beydoun has received personal compensation for activities, compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Baxalta Grifols, Xenoport, MT Pharma, Sarepta, Alexion, CSL, Daiichi and Pfizer. Dr. Rodriguez De Rivera Garrido has nothing to disclose. Dr. Rottoli has received personal compensation for activities with Almirall, Bayer Pharmaceuticals, Biogen Idec, Genzyme Corporation, Merck & Co., Novartis, Teva and Roche. Dr. Piehl has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Chugai. Dr. Van Damme has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Cytokinetics, Pfizer and Treeway. Dr. Vu has received personal compensation for speaking activities with Alexion, MT Pharma and Allergan. Dr. Vu has received research support from Alexion, Biogen, UCB Pharma, RA Pharma, Cytokinetics, Grifols, Behring, ARGX and Amylyx. Dr. Ulrichts has nothing to disclose. Dr. Verschueren has nothing to disclose. Dr. Guglietta has nothing to disclose. Dr. de Haard has nothing to disclose. Dr. Leupin is an employee of Argenx. Dr. Verschuuren has received research support from Argenx.

Clinical Trials Plenary Session

Tuesday, April 24, 2018, 9:15 a.m. – 11:30 a.m. 

EMBARGOED FOR RELEASE UNTIL 12:01 AM ET ON FRIDAY, APRIL 20, 2018

A Phase 3, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Eptinezumab for the Preventive Treatment of Chronic Migraine: Results of the PROMISE-2 (Prevention of Migraine via Intravenous Eptinezumab Safety and Efficacy 2) Trial

Richard B. Lipton, MD, FAAN; Joel Saper, MD, FAAN; Messoud Ashina; David Biondi, DO, FAAN; Suman Bhattacharya; Joe Hirman; Barbara Schaeffler; Roger Cady 

Objective: Evaluate the efficacy and safety of intravenous (iv) eptinezumab for preventive treatment of chronic migraine (CM). Background: Calcitonin gene-related peptide (CGRP) plays an important role in migraine pathophysiology. Eptinezumab, a humanized, anti-CGRP monoclonal antibody with 100% bioavailability following iv administration, selectively and potently inhibits CGRP. Design/Methods: Adults with CM (ICHD-3 beta) and were randomized (1:1:1) to eptinezumab 100 mg, 300 mg, or placebo. Infusion was administered on Day 0 and at Week 12. The primary endpoint was change from baseline in monthly migraine days (MMD) over Weeks 1-12. Key secondary endpoints included ≥75% reduction in MMD over Weeks 1-12 and Weeks 1-4, ≥50% reduction in MMD over Weeks 1-12, and percentage of subjects with migraine on Day 1 postinfusion. Results: Efficacy analysis included 1072 subjects. Mean baseline MMD in the 100-mg, 300-mg, and placebo groups were 16.1, 16.1, and 16.2, respectively. Reductions from baseline in MMD over Weeks 1-12 were greater with eptinezumab 100 mg (-7.7 [p<0.0001]) and 300 mg (-8.2 [p=0.0001]) vs placebo (-5.6). Significantly more subjects achieved ≥75% reduction in MMD over Weeks 1-12 with eptinezumab 100 mg (26.7% [p=0.0001]) and 300 mg (33.1% [p<0.0001]) vs placebo (15.0%). The ≥75% reductions in MMD over Weeks 1-4 were similar. Results favored eptinezumab for ≥50% reduction in MMD over Weeks 1-12: 100 mg (57.6% [p<0.0001]) and 300 mg (61.4% [p<0.0001]) vs placebo (39.3%). The percentage of subjects with migraine on Day 1 postinfusion was reduced from baseline by 50.3% (p=0.0001) for 100 mg and 51.6% (p<0.0001) for 300 mg vs 27.1% for placebo. The safety profile was consistent with previous clinical trials of eptinezumab. Conclusions: In subjects with CM, a single dose of eptinezumab 100 mg and 300 mg significantly reduced MMD for 12 weeks. Significant benefits occurred on the first day postinfusion and were sustained for 3 months.

Study Supported By: Alder BioPharmaceuticals, Inc., Bothell, WA, USA.

Disclosures: Dr Lipton has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alder, Allergan, American Headache Society, Amgen, Autonomic Technologies, Avanir, Boston Scientific, Bristol Myers Squibb, Colucid, Dr. Reddys, Eli Lilly, eNeura Therapeutics, GlaxoSmithKlein, Merck, Pernix, Novartis, Pfizer, Supernus, Teva, Trigemina, Vector and Vedanta. Dr Lipton holds stock options in eNeura Therapeutics (a company without commercial products). Dr. Saper has received personal compensation for activities compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Amgen, Autonomic Technologies, Eli Lilly, Dr Reddy, Teva and Supernus Pharm & Migraine Research Foundation. Dr. Saper has received research support from Achelios, GlaxoSmithKline, Astellas, Merck, Vanda, Alder, Allergan, Amgen, Inc., Autonomic Technologies, Inc., Cerephex Corporation, Daiichi Sankyo, Dr. Reddy’s Laboratories Ltd., Eli Lilly, Labrys Biologics, Pfizer, Inc., Scion Neurostim, LLC, Winston Laboratories, Nu Pathe, Johnson & Johnson (Ethicon), Purdue Pharma, Supernus, Teva and the Tian & Migraine Research Foundation. Dr. Ashina has received personal compensation for consulting activities with Alder BioPharmaceuticals, Allergan, Amgen, Alder, ATI, Eli Lilly, Novartis and Teva. Dr. Biondi is a full-time employee of Alder BioPharmaceuticals. Dr. Bhattacharya is a full-time employee of Alder BioPharmaceuticals. Dr. Hirman has received personal compensation as a consultant for Alder BioPharmaceuticals. Dr. Schaeffler is a full-time employee of Alder BioPharmaceuticals. Dr. Cady is a full-time employee of Alder BioPharmaceuticals.