Abstract Details

Title Intravenous and Intrathecal Onasemnogene Abeparvovec Gene Therapy in Symptomatic and Presymptomatic Spinal Muscular Atrophy: Long-Term Follow-Up Study

Topic Child Neurology and Developmental Neurology

Presentation(s) S34 - Child Neurology and Developmental Neurology 2 (1:12 PM-1:24 PM)

Poster/Presentation
Number 002

Objective Examine the long-term safety and durability of intravenous or intrathecal onasemnogene abeparvovec in symptomatic and presymptomatic patients with spinal muscular atrophy (SMA) who enrolled into the LT-002 study (NCT04042025).

Background Patients who received intravenous (STR1VE-US; STR1VE-EU; STR1VE-AP; SPR1NT) and intrathecal (STRONG) onasemnogene abeparvovec demonstrated improved survival and motor function versus natural history.

Design/Methods Long-term safety was assessed by medical history/record review, physical examination, laboratory evaluation, and pulmonary/cardiac assessments. Efficacy was assessed by developmental milestones and Hammersmith Functional Motor Scale Expanded (HFMSE).

Results As of May 23, 2022, 81 patients (intravenous, n=63 [symptomatic, n=38; presymptomatic, n=25]; intrathecal, n=18) were enrolled in LT-002, with a mean (range) follow-up of 3.4 (1.0–4.3) and 3.6 (2.6–4.3) years for the intravenous and intrathecal cohorts, respectively. There were no deaths or treatment-emergent adverse events (TEAEs) resulting in discontinuation. The most frequently reported TEAEs were gastroenteritis, nasopharyngitis, pneumonia, respiratory distress, and viral infection. All patients survived and maintained developmental milestones with a mean (range) age at cutoff of 3.7 (2.4–4.7) and 5.3 (3.4–7.4) years for the intravenous and intrathecal cohorts, respectively. Only one patient required permanent ventilation. Twenty-seven patients achieved new developmental milestones (presymptomatic-intravenous, n=6; symptomatic-intravenous, n=16; intrathecal, n=5); more than half (n=16) did so without add-on therapy. Improvements in HFMSE were clinically significant (≥3 points; presymptomatic-intravenous, 81.25%; symptomatic-intravenous, 66.6%; intrathecal, 50%). No patients treated presymptomatically required ventilatory/nutritional support; few symptomatic patients required ventilatory (intravenous-symptomatic, 32%; intrathecal, 5.6%) or feeding (intravenous-symptomatic, 20%; intrathecal, 0%) support at cutoff. Most patients fed orally (intravenous, 95%; intrathecal, 100%). The majority (57/81) never received add-on therapy. Of those receiving add-on therapy, half did not achieve a new developmental milestone after initiation of add-on therapy.

Conclusions Intravenous/intrathecal onasemnogene abeparvovec demonstrates consistent, substantial, and durable efficacy and no new safety signals in symptomatic and presymptomatic patients with SMA.

Authors/Disclosures
Basil T. Darras, MD (Children'S Hosp Boston Harvard Med School) PRESENTER	The institution of Dr. Darras has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Dr. Darras has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Amicus. The institution of Dr. Darras has received research support from National Institutes of Health/National Institute of Neurological Disorders and Stroke,. The institution of Dr. Darras has received research support from Slaney Family Fund for SMA. The institution of Dr. Darras has received research support from Spinal Muscular Atrophy Foundation. The institution of Dr. Darras has received research support from CureSMA. The institution of Dr. Darras has received research support from Working on Walking Fund . The institution of Dr. Darras has received research support from CHERISH, CS2/CS12 . The institution of Dr. Darras has received research support from Biogen for CS11. The institution of Dr. Darras has received research support from AveXis. The institution of Dr. Darras has received research support from Sarepta Pharmaceuticals. The institution of Dr. Darras has received research support from PTC Therapeutics. The institution of Dr. Darras has received research support from Roche. The institution of Dr. Darras has received research support from Santhera. The institution of Dr. Darras has received research support from Scholar Rock. The institution of Dr. Darras has received research support from Fibrogen. The institution of Dr. Darras has received research support from Summit. Dr. Darras has received publishing royalties from a publication relating to health care. Dr. Darras has received publishing royalties from a publication relating to health care.
	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 $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 Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PepGen. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Epirium Bio. 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 Solid Biosciences. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Astellas Pharma. 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 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. The institution of Dr. Day has received research support from AMO Pharma. The institution of Dr. Day has received research support from AnnJi. Dr. Day has received research support from CureSMA. The institution of Dr. Day has received research support from Muscular Dystrophy Association. The institution of Dr. Day has received research support from Ionis Pharmaceuticals. The institution of Dr. Day has received research support from NMD Pharma. The institution of Dr. Day has received research support from SMA Foundation. Dr. Day has received intellectual property interests from a discovery or technology relating to health care.
Yin-Hsiu Chien	Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Biogen. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amicus. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Avexis/Norvatis. Yin-Hsiu Chien has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. The institution of Yin-Hsiu Chien has received research support from Sanofi Genzyme.
	No disclosure on file
	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.
	No disclosure on file
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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