Abstract Details

Title Long-Term Follow-Up of Onasemnogene Abeparvovec Gene Therapy in Patients with Spinal Muscular Atrophy Type 1

Topic Child Neurology and Developmental Neurology

Presentation(s) P7 - Poster Session 7 (8:00 AM-9:00 AM)

Poster/Presentation
Number 4-006

Objective Evaluate long-term safety and efficacy of onasemnogene abeparvovec in patients with spinal muscular atrophy type 1 (SMA1; biallelic SMN1 mutations/deletions and two SMN2 copies) who enrolled into the LT-001 study (NCT03421977).

Background In the Phase I trial (START; NCT02122952), SMA1 patients who received the proposed therapeutic dose of onasemnogene abeparvovec (n=12) demonstrated substantially improved outcomes versus natural history.

Design/Methods The primary objective was to evaluate long-term safety assessed by medical history/record review, physical examination, laboratory evaluation, and pulmonary assessments. Efficacy was evaluated by assessing developmental milestones.

Results As of May 23, 2022, 13 patients (low-dose, n=3; therapeutic dose, n=10) were enrolled and followed for a mean of 95.1 (low-dose) and 83.5 (therapeutic dose) months. The oldest patient was 8.5 years of age (8.0 years post-dosing). In five patients, respiratory events and dehydration were reported. No deaths, serious treatment-emergent adverse events related to treatment, or any late-onset treatment events were reported. All patients who received the therapeutic dose survived, were free of permanent ventilation (mean [range] age at last data cut, 7.1 [6.6–7.9] years), and have maintained achieved developmental milestones. Three have achieved a new developmental milestone of standing with assistance (two without add-on therapy and one with nusinersen add-on). One patient in the low-dose cohort also achieved new developmental milestones (head control, sitting with support). Only three of 10 patients receiving the therapeutic dose required respiratory support, a decrease from five of 10 in December 2019. Four of 10 patients did not require any non-mechanical feeding support; all 10 fed orally. Four of 10 patients receiving the therapeutic dose never received add-on therapy. Of the six remaining, two started risdiplam, three switched from nusinersen to risdiplam, and one discontinued nusinersen.

Conclusions Onasemnogene abeparvovec continues to demonstrate a favorable risk-benefit profile and durable efficacy up to 8 years post-dosing.

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.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Lesa Mehl	Lesa Mehl has received personal compensation for serving as an employee of AveXis / Novartis Gene Therapies / Novartis Institutes for Biomedical Research, Inc. Lesa Mehl has stock in Novartis.
Anne M. Connolly, MD, FAAN (Nationwide Children's Hospital)	Dr. Connolly has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Edgewise Therapeutics. Dr. Connolly has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Octapharma. Dr. Connolly has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Connolly has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. The institution of Dr. Connolly has received research support from Muscular Dystrophy Association. The institution of Dr. Connolly has received research support from NIH.

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