Efficacy and Safety Results of the Avalglucosidase alfa Phase 3 COMET Trial in Late-Onset Pompe Disease Patients (4195)

Objective: Results (Baseline to Week 49) of the double-blinded Phase 3 COMET trial (NCT02782741/Sanofi Genzyme) comparing avalglucosidase alfa (n=51) and alglucosidase alfa (n=49) in treatment-naïve patients with late-onset Pompe disease (LOPD) are reported.

Background: Avalglucosidase alfa is a recombinant human GAA enzyme replacement therapy specifically designed for enhanced M6P-receptor targeting and enzyme uptake aimed at increased glycogen clearance and improvement of clinical efficacy as compared to alglucosidase alfa.

Design/Methods: The primary objective was to determine the effect of avalglucosidase alfa on respiratory muscle function, measured by upright forced vital capacity (FVC) %predicted. Secondary/other objectives include the effect of avalglucosidase alfa on functional endurance, inspiratory and expiratory muscle strength, lower and upper extremity muscle strength, motor function, and health-related quality of life, and safety.

Results: Treatment with avalglucosidase alfa resulted in greater improvements in upright FVC %predicted at all timepoints and a 2.43% greater increase in FVC %predicted compared to alglucosidase alfa at Week 49. The primary study objective, achieving statistical non-inferiority, was met (p=0.0074) and testing for superiority was borderline significant (p=0.0626). Avalglucosidase alfa treatment resulted in greater improvements in the 6-Minute Walk Test (6MWT) (meters and %predicted), with 30.01-m and 4.71% greater increases, respectively. Similarly, positive results for avalglucosidase alfa were seen for all secondary and other efficacy endpoints. Treatment-emergent adverse events (AEs) were reported in 86.3% of avalglucosidase alfa-treated and 91.8% of alglucosidase alfa-treated participants. Five participants withdrew, four due to AEs, all in the alglucosidase alfa arm. Serious AEs were reported in 8 avalglucosidase alfa-treated and 12 alglucosidase alfa-treated participants. IgG antidrug antibody responses were similar in both groups. High titers and neutralizing antibodies were more common for alglucosidase alfa.

Conclusions: These results demonstrate substantial improvements in clinically meaningful outcome measures as well as a more favorable safety profile in patients with LOPD treated with avalglucosidase alfa compared to alglucosidase alfa.

Disclosure: Dr. Kushlaf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. Dr. Kushlaf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Kushlaf has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. Dr. Kushlaf has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Genzyme. Dr. Kushlaf has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Akcea. Dr. Kushlaf has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Catalyst Pharmaceuticals . Prof. Attarian has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SANOFI, Pfizer LFB, Alnylam Biogen . Prof. Attarian has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for SANOFI, Biogen. The institution of Prof. Attarian has received research support from National Institut of Health . Joao Lindolfo Borges has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eurofarma. Francoise Bohour has nothing to disclose. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis/Norvatis. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Yin-Hsiu Chien has received research support from Biogen. The institution of Yin-Hsiu Chien has received research support from Sanofi Genzyme. Young-Chul Choi has nothing to disclose. Dr. Clemens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Clemens has received personal compensation in the range of $500-$4,999 for serving as a Consultant for F. Hoffman-La Roche. The institution of Dr. Clemens has received research support from NS Pharma. The institution of Dr. Clemens has received research support from ReveraGen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Affinia Therapeutics. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Audentes. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Cytokinetics. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. Dr. Day has received intellectual property interests from a discovery or technology relating to health care. Jordi Diaz-Manera has nothing to disclose. Sevim Erdem-Ozdamar has nothing to disclose. The institution of Ozlem Alpan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi-Genzyme . The institution of Ozlem Alpan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Takeda. Ozlem Alpan has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prevail . Ozlem Alpan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Genzyme . The institution of Ozlem Alpan has received research support from Sanofi genzyme . The institution of Ozlem Alpan has received research support from Shire HGT . The institution of Ozlem Alpan has received research support from Amicus. Ozlem Alpan has received intellectual property interests from a discovery or technology relating to health care. Sergey Illarioshkin has nothing to disclose. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi/Genzyme. Priya Kishnani, MD has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi/Genzyme. Priya Kishnani, MD has received research support from Sanofi/Genzyme. Anna Kostera-Pruszczyk has nothing to disclose. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Ladha has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Ladha has received research support from Biogen. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Abbvie. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion Pharmaceuticals. Dr. Mozaffar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Mozaffar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Modis Therapeutics. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acceleron. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi-Genzyme. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Neuromuscular Disease Foundation. The institution of Dr. Mozaffar has received research support from NIH. The institution of Dr. Mozaffar has received research support from Muscular Dystrophy Association. The institution of Dr. Mozaffar has received research support from The Myositis Association. The institution of Dr. Mozaffar has received research support from Sanofi-Genzyme. The institution of Dr. Mozaffar has received research support from Orphazyme. The institution of Dr. Mozaffar has received research support from Argenx. The institution of Dr. Mozaffar has received research support from Bristol-Myers Squibb. The institution of Dr. Mozaffar has received research support from Valerion Therapeutics. The institution of Dr. Mozaffar has received research support from Momenta. The institution of Dr. Mozaffar has received research support from Amicus Therapeutics. The institution of Dr. Mozaffar has received research support from Spark Therapeutics. The institution of Dr. Mozaffar has received research support from Audentes Therapeutics. The institution of Dr. Mozaffar has received research support from Cartesian. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Study Section Member with NIH. Dr. Mozaffar has received personal compensation in the range of $500-$4,999 for serving as a Director, Virtual Course on Inclusion Body Myositis with Muscular Dystrophy Association. Dr. Mozaffar has received personal compensation in the range of $0-$499 for serving as a Speaker with California Neurological Association. Dr. Mozaffar has a non-compensated relationship as a Director, Annual Muscle Course with American Academy of Neurology that is relevant to AAN interests or activities. Mark Roberts has nothing to disclose. Volker Straub has nothing to disclose. Dr. Toscano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi Genzyme. The institution of Ans Van Der Ploeg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme . The institution of Ans Van Der Ploeg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. The institution of Ans Van Der Ploeg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics . The institution of Ans Van Der Ploeg has received research support from Sanofi Genzyme. Kristina an Haack has received personal compensation for serving as an employee of Sanofi. An immediate family member of Kristina an Haack has received personal compensation for serving as an employee of Sanofi. Christopher Hug has received personal compensation for serving as an employee of Sanofi. Christopher Hug has received stock or an ownership interest from Sanofi. The institution of an immediate family member of Christopher Hug has received research support from NIH. Olivier Huynh-Ba has received personal compensation for serving as an employee of Sanofi. TIANYUE ZHOU has received personal compensation for serving as an employee of Sanofi. TIANYUE ZHOU has received stock or an ownership interest from Sanofi. Judith Johnson has received personal compensation for serving as an employee of Sanofi. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EcoR1 Capital, LLC. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cello Health BioConsulting, previously Defined Health. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for CSL Behring. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Octapharma. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ArgenX. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Spark Therapeutics. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for RAF-5. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Houston NeuroCare. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Shire. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Catalyst. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for CSL Behring. The institution of Dr. Dimachkie has received research support from CSL Behring. The institution of Dr. Dimachkie has received research support from Orphazyme. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Benedikt Schoser, 18260 has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi Genzyme. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofo Genzyme. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Nexien. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. Benedikt Schoser, 18260 has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Audentes. Benedikt Schoser, 18260 has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. 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