Abstract Details

Title A 104-week delayed-start analysis of PASADENA (Phase II study evaluating the safety and efficacy of prasinezumab in early Parkinson’s disease)

Topic Movement Disorders

Presentation(s) S16 - Movement Disorders: PD Biomarkers and Clinical Trials (4:54 PM-5:06 PM)

Poster/Presentation
Number 008

Background PASADENA Part 1 did not meet the primary endpoint (Movement Disorders Society–Unified Parkinson’s disease Rating Scale [MDS-UPDRS] sum of Parts I+II+III); however, prasinezumab-treated patients showed less motor progression compared with placebo.

Objective

To describe the effect of prasinezumab on motor progression in early Parkinson’s disease (ePD) using a delayed-start analysis of Part 2 (Week 104) of the Phase II PASADENA study (NCT03100149).

Design/Methods Individuals with ePD (diagnosis ≤2 years at screening; Hoehn & Yahr Stages I–II) were randomised to receive intravenous prasinezumab every 4 weeks (low or high dose) for 104 weeks (early-start group), or placebo for 52 weeks followed by prasinezumab (low or high dose) for 52 weeks (delayed-start group).

Results Worsening from baseline in MDS-UPDRS Part III scores was less in the early-start group (n=204) versus the delayed-start group (n=105) at Week 52 (5.02 [SE: 0.673] points vs. 6.25 [0.911] points, respectively) and at Week 104 (9.18 [0.994] vs. 11.12 [1.376] points, respectively), with the largest group difference in the bradykinesia subscore. Fewer patients in the early-start group (79.1%) reached a ≥5-point increase in MDS-UPDRS Part III versus the delayed-start group (89.5%) (hazard ratio: 0.77 [80% CI 0.66–0.91]). Digital motor scores were consistent with these results.

Conclusions After 2 years, prasinezumab-treated individuals showed less motor progression on MDS-UPDRS Part III in the early-start versus the delayed-start group. The ongoing Phase IIb PADOVA (NCT04777331) study will further assess efficacy and safety of prasinezumab in people with ePD on stable symptomatic treatment.

Authors/Disclosures
Gennaro Pagano, MD, PhD, eMBA (F. Hoffmann-La Roche Ltd) PRESENTER	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.
	No disclosure on file
Annabelle Monnet (F. Hoffmann-La Roche Ltd)	No disclosure on file
	No disclosure on file
	No disclosure on file
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.
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.
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.
	No disclosure on file
	No disclosure on file
	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.
	No disclosure on file
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.
Tania Nikolcheva	No disclosure on file