Abstract Details

Title NEO1 and NEO-EXT Studies: Long-Term Safety of Repeat Avalglucosidase Alfa Dosing for 4.5 Years in Patients With Late-Onset Pompe Disease

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) P5 - Poster Session 5 (5:30 PM-6:30 PM)

Poster/Presentation
Number 12-003

Objective Evaluate long-term safety of avalglucosidase alfa repeat dosing in late-onset Pompe disease (LOPD).

Background In NEO1 (NCT01898364), safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of avalglucosidase alfa dosing (5, 10, or 20 mg/kg qow) for 6 months were evaluated in LOPD patients either treatment-naïve (Naïve) or having received alglucosidase alfa for ≥9 months (Switch).

Design/Methods After NEO1 completion, participants were invited to enter NEO-EXT (NCT02032524), an ongoing NEO1 extension primarily evaluating long-term safety and pharmacokinetics of repeat avalglucosidase alfa dosing over 6 years. During 2016, NEO-EXT participants switched to avalglucosidase alfa 20 mg/kg qow.

Results

Interim safety results after 4.5 years of NEO-EXT are reported. At NEO1 enrollment, mean ages were: Naïve: 44.8 (SD:20.3, range:20-78) years; Switch: 46.7 (SD:14.1, range:21-68) years. 19/24 NEO1 participants entered NEO-EXT (8/10 Naïve; 11/14 Switch); 17 currently participate (7/8 Naïve; 10/11 Switch); 2 discontinued NEO-EXT (personal reasons). By May 2018, total infusions reached 731 (Naïve) and 1174 (Switch); mean infusions were Naïve: 73 (SD:43, range:9-113) and Switch: 84 (SD:40, range:8-118). Mean avalglucosidase alfa exposure duration reached 1025 (SD:611, range:109-1572) days for Naïve and 1179 (SD:570, range:102-1658) days for Switch. Treatment-emergent adverse events (AEs) were generally mild across doses. Most frequently reported treatment-related AEs are unchanged since the NEO-EXT 3.5-year review: nausea, fatigue, and headache (3 participants each); dizziness, dyspnea, erythema, myalgia, muscle spasms, and rash (2 participants each). One Switch participant discontinued NEO1 for a study drug-related serious AE (respiratory distress/chest discomfort); no deaths/life-threatening serious AEs have occurred. Anti-avalglucosidase IgG/IgM antibodies developed in 9/10(90%) Switch (median titer:1600, range:200-51,200) and 9/14(64%) Naïve (median titer:400, range:50-12,800) participants. No participant developed IgE antibodies or tested positive for enzyme activity inhibition.

Conclusions In NEO-EXT, the avalglucosidase alfa safety profile is consistent with the initial 6 months’ treatment during NEO1, with no additional participants developing anti-avalglucosidase alfa IgG/IgM antibodies or new allergic reactions.

Authors/Disclosures
Mazen M. Dimachkie, MD, FAAN (University of Kansas Medical Center) PRESENTER	Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 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 $0-$499 for serving as a Consultant for Catalyst. Dr. Dimachkie has received personal compensation in the range of $0-$499 for serving as a Consultant for Takeda. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medlink. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CSL Behring. Dr. Dimachkie has received personal compensation in the range of $0-$499 for serving as a Consultant for Astellas. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Dianthus. Dr. Dimachkie has received personal compensation in the range of $0-$499 for serving as a Consultant for TACT / Treat NMD. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cabaletta Bio. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Clinical Neurological Society of America, Inc . Dr. Dimachkie has received personal compensation in the range of $0-$499 for serving as a Consultant for Ig Society, Inc. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abcuro. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Horizon/Immunovant. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ipsen. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvig. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for ��ɫ�� (AAN). Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for American Association of Neuromuscular and Electrodiagnostic Medicine (AANEM). Dr. Dimachkie has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Annexon Biosciences. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AstraZeneca. Dr. Dimachkie has received personal compensation in the range of $0-$499 for serving as a Consultant for Candid Therapeutics. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Creyon Bio, Inc.. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nuvig Therapeutics. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB Biopharma. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Vertex Pharmaceuticals. Dr. Dimachkie has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Fortrea. Dr. Dimachkie has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Kriya Therapeutics. The institution of Dr. Dimachkie has received research support from NIH. The institution of Dr. Dimachkie has received research support from The Myositis Association. The institution of Dr. Dimachkie has received research support from Biosensics. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received intellectual property interests from a discovery or technology relating to health care. Dr. Dimachkie has received publishing royalties from a publication relating to health care. Dr. Dimachkie has received publishing royalties from a publication relating to health care.
Richard J. Barohn, MD, FAAN (University of Missouri)	Dr. Barohn has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for NuFactor. The institution of Dr. Barohn has received research support from FDA OPD R01. Dr. Barohn has received intellectual property interests from a discovery or technology relating to health care.
Priya Kishnani, MD (Duke University)	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 $10,000-$49,999 for serving as a Consultant for Amicus Therapeutics. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Maze Therapeutics. Priya Kishnani, MD has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for JCR Pharmaceutical. Priya Kishnani, MD has received personal compensation in the range of $500,000-$999,999 for serving as a Consultant for Asklepios Biopharmaceutical Inc. (AskBio). 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 personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus Therapeutics. 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 Baebies, Inc.. The institution of Priya Kishnani, MD has received research support from Sanofi/Genzyme. Priya Kishnani, MD has received research support from Amicus Therapeutics. Priya Kishnani, MD has received intellectual property interests from a discovery or technology relating to health care. Priya Kishnani, MD has received intellectual property interests from a discovery or technology relating to health care.
Shafeeq Ladha, MD (Barrow Neurological Institute)	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 $10,000-$49,999 for serving as a Consultant for Sanofi. Dr. Ladha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Ladha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Ladha has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurosense. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Rapa Therapeutics. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Ladha has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sanofi. Dr. Ladha has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Genentech. The institution of Dr. Ladha has received research support from Biogen. The institution of Dr. Ladha has received research support from Sanofi. Dr. Ladha has received publishing royalties from a publication relating to health care.
	No disclosure on file
Loren D. Pena	No disclosure on file
Sabrina Sacconi, MD	Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LUPIN. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for SANOFI. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIOGEN. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AMICUS. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Sacconi 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. Sacconi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FULCRUM THERAPEUTICS. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for AXELYS. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for OLOGY. The institution of Dr. Sacconi has received research support from Solve FSHD.
Philip Van Damme	The institution of Dr. Van Damme has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for QurAlis. The institution of Dr. Van Damme has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Argenx. The institution of Dr. Van Damme has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for VectorY. The institution of Dr. Van Damme has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for NRG Therapeutics. The institution of Dr. Van Damme has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. The institution of Dr. Van Damme has received research support from CSL Behring.
	No disclosure on file
Kristina an Haack	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Benedikt Schoser	Benedikt Schoser has received personal compensation for serving as an employee of Alexion. Benedikt Schoser has received personal compensation for serving as an employee of Argenx. Benedikt Schoser has received personal compensation for serving as an employee of Amicus. Benedikt Schoser has received personal compensation for serving as an employee of Astellas. Benedikt Schoser has received personal compensation for serving as an employee of Denali. Benedikt Schoser has received personal compensation for serving as an employee of Avidity . Benedikt Schoser has received personal compensation for serving as an employee of Sanofi. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Taysha. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Astellas. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Encoded. Benedikt Schoser has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kedrion.

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