Onasemnogene Abeparvovec Gene Therapy in Presymptomatic Spinal Muscular Atrophy (SMA): SPR1NT Study Update in Children with 3 Copies of SMN2 (4163)

Objective: Evaluate the safety/efficacy of onasemnogene abeparvovec (formerly AVXS-101) in presymptomatic SMA patients with 3 copies of the survival motor neuron 2 gene (SMN2).

Background: SMA causes loss of motor/respiratory function due to SMN1 deletion/mutation. Copies of SMN2 modify disease severity. A range of phenotypes may occur with 3SMN2 with approximately 85% developing symptoms in infancy and not being able to walk independently without intervention.

Design/Methods: SPR1NT (NCT03505099) is an ongoing multicenter, open-label, Phase III study. Asymptomatic patients expected to develop SMA (Cohort 2: 3SMN2, ≤6 weeks) received a one-time intravenous infusion and are assessed through 24 months. Primary outcome: standing unassisted for ≥3 seconds. Secondary outcome: independent walking. Safety outcomes: incidence of adverse events (AEs)/serious AEs.

Results: As of 11 June 2020, 15 patients in Cohort 2 were enrolled (enrollment complete). Median age (range) at last visit (months): 15.2 (3.3–21.1); median follow-up time (range) at last visit (months): 14.5 (2.0–19.9). All patients are alive and none used ventilatory or feeding tube support at any time. Eight of 15 Cohort 2 patients had achieved the primary efficacy endpoint of stands alone within the normal developmental window (16.9 months, De Onis 2006). The remaining 7 patients were all younger than 16.9 months of age. Six patients also walked alone within the normal developmental window (17.6 months, De Onis 2006); remaining patients were younger than 17.6 months of age. Within the whole SPR1NT study population 30/30 patients (14 2SMN2, 15 3SMN2, and 1 4SMN2 patient included only in the safety population) experienced ≥1 AE; 17/30 experienced treatment-related AEs. 7/13 experienced a serious AE, but all resolved and were considered unrelated to treatment.

Conclusions: Patients in this cohort treated with onasemnogene abeparvovec have achieved gross motor milestones similar to non-SMA, typically developing peers, demonstrating a significant therapeutic benefit.

Disclosure: Kevin Strauss has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sarepta. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Pfizer. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis. Dr. Muntoni has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. The institution of Dr. Muntoni has received research support from European Commission. The institution of Dr. Muntoni has received research support from Medical Research Council. The institution of Dr. Muntoni has received research support from Biogen. The institution of Dr. Muntoni has received research support from Muscular Dystrophy UK. The institution of Dr. Muntoni has received research support from MDA USA. The institution of Dr. Muntoni has received research support from Sarepta. The institution of Dr. Muntoni has received research support from Association Francoise Myopathies. Dr. Muntoni has received personal compensation in the range of $0-$499 for serving as a Clinical expert with UK NICE Committee. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Michelle Farrar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Kyoko Saito has nothing to disclose. 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 an Expert Witness for Vertex. Dr. Mendell has received research support from Sarepta. The institution of Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis. Dr. McMillan has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for AveXis. The institution of Dr. McMillan has received research support from Roche. Dr. Swoboda has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Swoboda has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Swoboda has received research support from Biogen. Dr. Kwon has nothing to disclose. Dr. Zaidman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Zaidman has received research support from Biogen. Dr. Chiriboga has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentec. Dr. Chiriboga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Chiriboga has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avexis. Dr. Chiriboga has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Dr. Chiriboga has received research support from Roche. The institution of Dr. Chiriboga has received research support from Avexis. The institution of Dr. Chiriboga has received research support from Biogen. The institution of Dr. Chiriboga has received research support from NIH. Dr. Chiriboga has received publishing royalties from a publication relating to health care. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta. Dr. Iannaccone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Iannaccone 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. Iannaccone has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis. The institution of Dr. Iannaccone has received research support from AveXis. The institution of Dr. Iannaccone has received research support from Biogen. The institution of Dr. Iannaccone has received research support from Sarepta. The institution of Dr. Iannaccone has received research support from PTC Therapeutics. The institution of Dr. Iannaccone has received research support from FibroGen. The institution of Dr. Iannaccone has received research support from ReveraGen. The institution of Dr. Iannaccone has received research support from MDA. The institution of Dr. Iannaccone has received research support from PPMD. The institution of Dr. Iannaccone has received research support from NIH. Dr. Iannaccone has received personal compensation in the range of $0-$499 for serving as a grant reviewer with NIH. Dr. Krueger has nothing to disclose. Dr. Parsons has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AveXis. Dr. Parsons has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. The institution of Dr. Parsons has received research support from AveXis. The institution of Dr. Parsons has received research support from Biogen. The institution of Dr. Parsons has received research support from Scholar Rock. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sarepta. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Shieh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Alexion. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for PTC. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Pfizer. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for CSL Behring. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Grifols. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Alexion. Dr. Shieh has received personal compensation in the range of $50,000-$99,999 for serving on a Speakers Bureau for Biogen. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Genentech. Dr. Shieh has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Avexis. Sarah Kavanagh has received personal compensation in the range of $100,000-$499,999 for serving as a Consultant for UCB Pharma. Sarah Kavanagh has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Colorado Prevention Center. Sarah Kavanagh has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for PureTech Health. Sarah Kavanagh has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Worldwide Clinical Trails. Deepa Chand has received personal compensation for serving as an employee of Novartis Gene Therapies. Deepa Chand has received stock or an ownership interest from Novartis. Deepa Chand has received publishing royalties from a publication relating to health care. Sitra Tauscher-Wisniewski has received personal compensation for serving as an employee of Novartis Gene Therapies. Thomas Macek has received personal compensation for serving as an employee of Novartis . Thomas Macek has received stock or an ownership interest from Novartis .