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).

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.