Abstract Details

Title Long-Term Follow-Up (LTFU) of Onasemnogene Abeparvovec Gene Therapy in Spinal Muscular Atrophy (SMA)

Topic Child Neurology and Developmental Neurology

Presentation(s) S4 - Child Neurology and Developmental Neurology (4:16 PM-4:24 PM)

Poster/Presentation
Number 003

Background

In the Phase I trial (START; NCT02122952), SMA type 1 patients who received a one-time high-dose (proposed therapeutic dose) infusion (n=12) demonstrated significantly improved outcomes versus untreated natural history. Patients from five intravenous and intrathecal studies may enroll in LT-002.

Objective

Evaluate long-term safety/efficacy of patients previously treated in the onasemnogene abeparvovec (formally AVXS-101) clinical development program who electively enrolled into LTFU studies LT-001 (NCT03421977) and LT-002 (NCT04042025).

Design/Methods

Primary objective: long-term safety. Patients have annual visits (five years) followed by annual phone contact (ten years). Assessments include medical history/record review, physical examination, laboratory evaluation, pulmonary assessments, and milestone maintenance. LT-002 is an additional LTFU study with 308 participants planned from other onasemnogene abeparvovec clinical trials. Enrollment is ongoing.

Results

As of 11 June 2020, 13 patients (low dose, n=3; therapeutic dose, n=10) were enrolled in LT-001. The oldest patients were aged 6.7 (low dose) and 6.1 (therapeutic dose) years. Serious adverse events were reported in 8/13 patients; however, none were considered related to treatment or led to study discontinuation. All patients who received the therapeutic dose have survived and are free of permanent ventilation (mean [range] age at last datacut: 5.2 [4.7–6.1] years; mean [range] time since dosing: 5.2 [4.6–6.2] years). These patients have either maintained all previously attained milestones or gained new milestones; two have newly achieved standing with assistance while not receiving concomitant nusinersen at any point. Of the ten enrolled patients who received the therapeutic dose, six did not require regular, daily respiratory support more than four years after dosing. Nusinersen treatment was ongoing in seven of 13 patients. As of 11 June 2020, six patients were enrolled in LT-002 with minimal follow-up.

Conclusions

Data suggest that onasemnogene abeparvovec shows a favorable risk:benefit profile, and continues to demonstrate durable efficacy.

Authors/Disclosures
Jerry R. Mendell, MD, FAAN (The Research Institute at Nationwide Children's Hospital) PRESENTER	Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vertex. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Mendell has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta Therapeutics . The institution of Dr. Mendell has received research support from Sarepta.
Richard S. Finkel, MD, FAAN (St. Jude Children's Research Hospital)	Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Capricor. Dr. Finkel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen. Dr. Finkel has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Finkel 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. Finkel has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. The institution of Dr. Finkel has received research support from AveXis. The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has received personal compensation in the range of $0-$499 for serving as a Speaker in workshop with National Academy of Sciences. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with EveryLife Foundation that is relevant to AAN interests or activities.
	No disclosure on file
Kevin Strauss	Kevin Strauss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis.
John W. Day, MD, PhD (Stanford University School of Medicine)	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.
	No disclosure on file
	No disclosure on file
Sitra Tauscher-Wisniewski	Sitra Tauscher-Wisniewski has received personal compensation for serving as an employee of Novartis Gene Therapies.
Matthew N. Meriggioli, MD, FAAN (Novartis Biomedical Research)	Dr. Meriggioli has received personal compensation for serving as an employee of Novartis Gene Therapies. Dr. Meriggioli has received stock or an ownership interest from Novartis.