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Abstract Details

AVXS-101 Gene-Replacement Therapy (GRT) in Spinal Muscular Atrophy Type 1 (SMA1): Long-Term Follow-Up From the Phase 1 Clinical Trial
Child Neurology and Developmental Neurology
S25 - Child Neurology: Spinal Muscular Atrophy: Treatments and Outcomes (1:55 PM-2:06 PM)
006

Infants with SMA1 rapidly lose the ability to swallow and breathe, do not achieve normal developmental milestones, fail to thrive, suffer from frequent pulmonary infections, and lose the ability to communicate before succumbing to the disease. AVXS-101, a one-time GRT, treats the genetic root cause of SMA, deletion/loss of function of the survival motor neuron (SMN1) gene. It is designed for immediate, sustained expression of SMN protein, allowing rapid onset and durable effect. In the phase 1 trial (NCT02122952), 15 SMA1 patients received a one-time intravenous dose of AVXS-101, 3 at a lower dose (cohort 1) and 12 at the proposed therapeutic dose (cohort 2). There was unprecedented event-free survival and developmental motor milestones (Mendell N Engl J Med 2017).

Report long-term follow-up study design and data from the phase 1 study of onasemnogene abeparvovec (AVXS-101) in SMA1.

Patients in the phase 1 study could rollover into a long-term follow-up study (NCT03421977). The primary objective is to collect long-term safety data by assessing incidence of serious adverse events, hospitalizations, and adverse events of special interest. Patients will have annual visits for 5 years followed by contact via phone annually for 10 years. Additionally, patient record transfers from their local physician and/or neurologist will be requested. Safety assessments will include medical history and record review, physical examination, clinical laboratory evaluation, and pulmonary assessments. Efficacy assessments will include physical examination to assess developmental milestones.

As of September 27, 2018, the oldest patients in cohort 1 and 2 are 59.2 and 52.1 months old, respectively, and free of permanent ventilation. Preliminary data, including survival and developmental milestones, will be presented. 

Patients treated with a one-time dose of AVXS-101 continue to gain strength, develop, and achieve new milestones, demonstrating a long-term, durable response.

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.
Kelly Lehman, MSN, CNP (Nationwide Children's Hospital- The Research Institute) Ms. Lehman has nothing to disclose.
Markus McColly No disclosure on file
Linda P. Lowes, PT PhD The institution of Ms. Lowes has received research support from Sarepta Therapeutics.
Lindsay N. Alfano, PT (Nationwide Children'S Hospital) Ms. Alfano has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ATOM International, Ltd (Amicus Therapeutics, Catabasis, Genethon, Italfarmaco, NS Pharma, Pfizer, PTC Therapeutics). Ms. Alfano has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sarepta Therapeutics. The institution of Ms. Alfano has received research support from Novartis Gene Therapies. The institution of Ms. Alfano has received research support from Sarepta Therapeutics. The institution of Ms. Alfano has received research support from Audentes Therapeutics/Astellas Gene Therapies. Ms. Alfano has received intellectual property interests from a discovery or technology relating to health care.
No disclosure on file
Megan Iammarino, PT (Nationwide Children'S Hospital) Dr. Iammarino has nothing to disclose.
Kathleen Church No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
No disclosure on file
Douglas Feltner No disclosure on file
Richard Shell No disclosure on file
Samiah A. Al-Zaidy, MD Dr. Al-Zaidy has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AveXis Inc.