highlights the groundbreaking work of Dr. Jerry Mendell and his team and further validates the clinically transformative nature of gene therapy in children with SMA Type 1.
The NEJM publication provides detailed data as of August 7, 2017, from the Phase 1, open-label, dose-escalating study, designed to evaluate the safety and tolerability of AVXS-101 in patients with SMA Type 1. The key measures of efficacy were the time from birth to an event, which was defined as either death or at least 16 hours per day of required ventilation support for breathing for 14 consecutive days in the absence of acute reversible illness or perioperatively, and video confirmed achievement of ability to sit unassisted. Additionally, several exploratory objective measures were assessed, including a standard motor milestone development survey and Childrens Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).
Event-free Survival and Safety
· Data as of August 7, 2017, showed no new events, and 15 of 15 (100%) patients were event-free at 20 months of age. The expected event-free survival rate at 20 months of age based on the natural history of the disease is eight percent. The median age at last follow-up was 25.7 months and 30.7 months for patients in the proposed therapeutic-dose cohort (Cohort 2) and low-dose cohort (Cohort 1), respectively.
· As has been previously reported, a total of five adverse events (AEs) in four patients were deemed treatment-related. Of these, two were serious adverse events (SAEs) experienced by two patients, and three were non-serious AEs experienced by two patients. All consisted of clinically asymptomatic liver enzyme elevations and were resolved with prednisolone treatment. There were no clinically significant elevations of gamma-glutamyl transferase, alkaline phosphatase or bilirubin and, as such, Hys Law was not met. Other non-treatment-related AEs were expected and were associated with SMA.
· A cumulative total of 297 AEs (five treatment-related AEs and 292 non-treatment related AEs) were reported as of August 7, 2017, following monitoring and source verification. Of these, 56 were determined to be SAEs and 241 were non-serious AEs.
· AVXS-101 appeared to have a favorable safety profile and to be generally well tolerated, with no new treatment-related safety or tolerability concerns identified.
Treatment Durability and Motor Milestone Achievement
· As of August 7, 2017, 11 of 12 patients (92%) in Cohort 2 have achieved and maintained CHOP-INTEND scores of >40 points.
· As of August 7, 2017, 11 of 12 patients (92%) in Cohort 2 achieved head control, nine of 12 patients (75%) could roll over and 11 of 12 patients (92%) could sit with assistance.
· As of August 7, 2017, 11 of 12 patients (92%) in Cohort 2 could sit unassisted for at least five seconds, 10 of 12 patients (83%) could sit unassisted for at least 10 seconds and nine of 12 patients (75%) could sit unassisted for 30 seconds or more.
· As of August 7, 2017, two patients in Cohort 2 could crawl, pull to a stand and stand and walk independently.
· All motor milestones have been assessed and adjudicated by an independent third-party reviewer using video evidence.