Abstract Details

Title Exploratory Analysis of PASADENA Open-label Extension Evaluating the Effect of Prasinezumab on the Progression of Motor Signs and Symptoms

Topic Movement Disorders

Presentation(s) S30 - Movement Disorders: Clinical Trials in Movement Disorders (2:00 PM-2:12 PM)

Poster/Presentation
Number 006

Background Prasinezumab is a humanized monoclonal antibody that binds aggregated alpha-synuclein with the potential to slow disease progression in Parkinson’s disease (PD).

Objective To compare the progression of the PASADENA population treated with prasinezumab to a matched real-world data sample from the Parkinson's Progression Markers Initiative (RWD-PPMI).

Design/Methods Early-stage PD participants of PASADENA received intravenous prasinezumab every 4 weeks (1500 mg or 4500 mg) for 104 weeks (early-start group) or placebo for 52 weeks (Part 1) followed by prasinezumab (1500 mg or 4500 mg) for 52 weeks (Part 2; delayed-start group). Following a wash-out period on average 7.4 months, 271 participants entered the 5-year open-label extension (OLE) receiving prasinezumab 1500 mg every 4 weeks (Part 3) and were included in the analysis, regardless of change in symptomatic therapy. After 3.5 years follow-up, MDS-UPDRS part III ON-state and MDS-UPDSR part II score were compared among early-start group (n=177), delayed-start group (n=94) and RWD-PPMI (n=303), using a mixed model for repeated measures.

Results Compared to the RWD-PPMI, PASADENA delayed- and early-start groups showed a slower decline (less increase in score) on MDS-UPDRS Part III ON-state: delayed-start group: -96% less progression (mean points [80% confidence interval]) (-4.9 [-6.75 to -3.04]), early-start group: -127% less progression (-6.5 [-7.96 to -5.03]); and on MDS-UPDRS Part II: delayed-start group: -38% less progression (-1.53 [-2.31 to -0.74]), early-start group: -43% less progression (-1.73 [-2.36 to -1.11]).

Conclusions Progression in the PASADENA OLE population was relatively small compared to the RWD-PPMI cohort, suggesting that prasinezumab slowed the progression of motor signs and symptoms of PD. These exploratory results need to be confirmed in a randomized controlled trial.

Authors/Disclosures
Patrik Brundin, MD, PhD (Roche) PRESENTER	Prof. Brundin has received personal compensation for serving as an employee of Roche. Prof. Brundin has stock in Acousort AB. Prof. Brundin has stock in Axial Therapeutics. Prof. Brundin has stock in F Hoffmann-La Roche. Prof. Brundin has stock in Enterin Inc. Prof. Brundin has stock in Kenai Therapeutics. The institution of an immediate family member of Prof. Brundin has received research support from NIH. Prof. Brundin has received personal compensation in the range of $500,000-$999,999 for serving as a Employee (Therapeutic Area Leader) with Roche. Prof. Brundin has a non-compensated relationship as a Member of International Linked Clinical Trials committee with Cure Parkinson's that is relevant to AAN interests or activities.
Gennaro Pagano, MD, PhD, eMBA (F. Hoffmann-La Roche Ltd)	Prof. Pagano has received personal compensation for serving as an employee of F.Hoffmann-La Roche Ltd. Prof. Pagano has stock in F.Hoffmann La Roche Ltd.
Annabelle Monnet (F. Hoffmann-La Roche Ltd)	No disclosure on file
Adriana Reyes	No disclosure on file
Tanya Simuni, MD, FAAN (Northwestern University Feinberg School of Medicien)	Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for cadia, AcureX, Adamas, AskBio, Amneal, Blue Rock Therapeutics, Caraway Therapeutics, Critical Path for Parkinson's Consortium (CPP), Denali, Michael J Fox Foundation, Neuroderm, Sanofi, Sinopia, Roche, Takeda and Vanqua Bio. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for of Koneksa, Neuroderm, Sanofi, UCB, AcureX, Adamas, AskBio, Biohaven, Denali, GAIN, Neuron23 and Roche. Dr. Simuni has received research support from Amneal, Biogen, Neuroderm, Prevail, Roche, and UCB and an investigator for NINDS, MJFF, Parkinson's Foundation.
Ronald Postuma, MD (Montreal General Hospital)	Dr. Postuma has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche, Biogen, Takeda, Theranexus, GE, Jazz, Curasen, Paladin, Inception Sciences, Phytopharmics, Vaxxinity, Merck. Dr. Postuma has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen/Partners. The institution of Dr. Postuma has received research support from CIHR, Weston Foundation, Webster Foundation, Roche, MJFF, Parkinson Canada, FRSQ, NIH.
Nicola Pavese, MD (Newcastle University)	Dr. Pavese has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial. Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. The institution of Dr. Pavese has received research support from Multiple System Atrophy Trust. The institution of Dr. Pavese has received research support from Parkinson's UK. The institution of Dr. Pavese has received research support from Independent Research Fund Denmark. The institution of Dr. Pavese has received research support from European Union. The institution of Dr. Pavese has received research support from MRC.
Fabrizio Stocchi	Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bial, Biogen, Sunovion, Lundbeck, UCB, Zambon, Chiesi, Lusofarmaco, Abbvie, Neuroderm, Kyowa, Synegile, Roche, Britannia, Sunovion, Blue Rock. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIAL, Zambon, Biogen, Roche, Synegile, Sunovion. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bial, Zambon, UCB, Kyowa, Sunovion.
Krzysztof Smigorski (F. Hoffmann-La Roche AG)	No disclosure on file
Valentina Gerbaldo	No disclosure on file
Riorge Thomas (Roche UK)	No disclosure on file
Hanno Svoboda (Roche)	No disclosure on file
Paulo P. Fontoura, MD, PhD, FAAN	Dr. Fontoura has received personal compensation for serving as an employee of F. Hoffmann La Roche. Dr. Fontoura has stock in Roche Pharmaceuticals.
Rachelle S. Doody, MD, PhD	Dr. Doody has received personal compensation for serving as an employee of F. Hoffman-LaRoche. Dr. Doody has stock in F. Hoffman-LaRoche.
Geoffrey A. Kerchner, MD, PhD (Genentech, Inc.)	Dr. Kerchner has received personal compensation for serving as an employee of F. Hoffmann-La Roche, Ltd.. Dr. Kerchner has stock in F. Hoffmann-La Roche, Ltd.. Dr. Kerchner has received publishing royalties from a publication relating to health care.
Azad Bonni, MD, PhD (F. Hoffmann-La Roche Ltd, Roche Innovation Center Basel)	Dr. Bonni has received personal compensation for serving as an employee of F.Hoffmann-La Roche Ltd. Dr. Bonni has stock in F.Hoffmann-La Roche Ltd.
Kenneth L. Marek, MD (IND)	Dr. Marek has received personal compensation for serving as an employee of IND. Dr. Marek has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for invicro. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for takeda. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denali. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Koneksa. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Xingimaging. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neuron23. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Marek has received research support from Michael J Fox Foundation.
Tania Nikolcheva	No disclosure on file