Abstract Details

Title NEO1/NEO-EXT Studies: Long-term Muscle Quantitative Magnetic Resonance Imaging and Functional Efficacy in Adults With Late-onset Pompe Disease (LOPD) on Avalglucosidase Alfa Treatment

Topic General Neurology

Presentation(s) P8 - Poster Session 8 (5:30 PM-6:30 PM)

Poster/Presentation
Number 4-010

Objective

To assess changes in muscle fat fraction (FF) and functional efficacy in patients with late-onset Pompe disease (LOPD) after long-term treatment with avalglucosidase alfa (AVA).

Background

NEO1 (NCT01898364) and NEO-EXT (NCT02032524 [NEO1 extension]) studied AVA, a recombinant human acid α-glucosidase enzyme replacement therapy designed for greater cellular uptake, in adults with LOPD.

Design/Methods

Participants were treatment-naïve (Naïve, n=10) or had received alglucosidase alfa for ≥9 months (Switch, n=14) at baseline, and received AVA (5, 10, or 20 mg/kg/every other week [qow]) for 6 months. 19 participants entered NEO-EXT receiving their NEO1 AVA dose until 2016; thereafter, all received AVA 20 mg/kg/qow. We report muscle quantitative magnetic resonance imaging (qMRI) Dixon FF changes from NEO1 baseline and exploratory efficacy data up to 8 years of follow-up (cut-off: February 16, 2023). Annualized slopes were derived from linear mixed-effects models.

Results

Baseline mean±SD hamstring %FF was Naïve: 37.8%±26.0% (n=6); Switch: 26.6%±19.3% (n=8) and quadriceps %FF was Naïve 9.8%±3.4% (n=6); Switch 13.0%±6.9% (n=8). FF% slope estimates (95% CI) for hamstring were Naïve: 1.853/year (0.962, 2.743); Switch: 1.130/year (0.284, 1.976) and for quadriceps were Naïve: 0.782/year (0.371, 1.193); Switch: 0.702/year (0.192, 1.212). These 8-year qMRI data continue the trend previously reported at 5 years. Slope estimates (95%CI) for forced vital capacity % predicted were Naïve: −0.392/year (−0.863, 0.079); Switch: −0.464/year (−0.880, −0.049) and for 6-minute walk test % predicted were Naïve: −1.165/year (−1.720, −0.611); Switch: −0.265/year (−0.719, 0.190). Compared to previously reported 6-year data, participants appear as clinically stable at 8 years.

Conclusions

These NEO-EXT results support the clinical utility of monitoring qMRI in LOPD patients, which may be a useful biomarker of early disease progression. qMRI evidenced a trend for stabilization in most participants, supporting the observed clinical stability during 8 years of follow-up. [On behalf of NEO-EXT Investigators] Funding: Sanofi.

Authors/Disclosures
Shafeeq Ladha, MD (Barrow Neurological Institute) PRESENTER	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.
Pierre Carlier	No disclosure on file
John Vissing, MD (Rigshospitalet)	Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Dyne Therapeutics. Prof. Vissing has received personal compensation in the range of $0-$499 for serving as a Consultant for Denali Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avidity Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Italfarmaco. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alexion. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NMD Pharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NMD Pharma. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Prof. Vissing has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Sarepta. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion Pharmaceuticals. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Johnson & Johnson (Janssen). Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Edgewise Therapeutics. Prof. Vissing has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for UCB. The institution of Prof. Vissing has received research support from Rigshospitalet. The institution of Prof. Vissing has received research support from Avidity. The institution of Prof. Vissing has received research support from Sanofi. The institution of Prof. Vissing has received research support from Roche. The institution of Prof. Vissing has received research support from AnnJi.
Mazen M. Dimachkie, MD, FAAN (University of Kansas Medical Center)	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.
Barry Byrne	Barry Byrne has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Barry Byrne has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Rocket Pharma. Barry Byrne has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Muscular Dystrophy Association.
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.
Eugen Mengel	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.
Jaya Trivedi, MD, FAAN (UT Southwestern Medical Center)	The institution of Dr. Trivedi has received research support from Avidity.
Peter Young	No disclosure on file
Kristina an Haack	No disclosure on file
Nicole Armstrong	No disclosure on file
Miossec Patrick (sanofi)	No disclosure on file
Nathan Thibault	Nathan Thibault has received personal compensation for serving as an employee of Sanofi. Nathan Thibault has stock in Sanofi.
Susan Sparks	Susan Sparks has received personal compensation for serving as an employee of Sanofi. Susan Sparks has stock in Sanofi.
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.
Jordi Diaz-Manera (Newcastle University)	Jordi Diaz-Manera has nothing to disclose.

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