AveXis Releases Favorable Data in Ongoing Phase 1 Test of SMA Gene Therapy, AVXS-101

AveXis recently reported favorable results from an ongoing Phase 1 clinical trial examining its candidate, AVXS-101, for the systematic delivery of gene therapy to young patients with spinal muscular atrophy (SMA). These preliminary results will help inform upcoming trials on gene therapy approaches.

The open-label, dose-escalation study evaluating the safety and efficacy of AVXS-101, delivered intravenously, has enrolled 15 patients diagnosed before 6 months of age, with two copies of the SMN2 backup gene. Participants are in one of two dosing cohorts: three patients, ages six to seven months at time of dosing, received a one-time dose of 6.7 X 10^13 vg/kg (cohort 1), and the other 12, ages 1 to 8 months at time of dosing, received 2.0 X 10^14 vg/kg (cohort 2). The data released is from the trial’s time period ending Dec. 31, 2015 (the same period as interim data released in January), and the company reported that AVXS-101 had a favorable safety profile and was generally well-tolerated. Ten serious adverse events reported, two of which were related to therapy, involving clinically asymptomatic, elevated liver function enzymes. These two cases have been resolved, the company said.

The trial’s primary outcome is safety and tolerability, and the secondary outcome measure is efficacy as defined by the time from birth to an “event,” defined either as death or time until a patient requires at least 16 hours/day of ventilation support  for 14 consecutive days. Exploratory outcome measures include motor function testing, assessed by several motor milestone surveys and tests, including the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND), a test developed to measure motor skills of patients with SMA type 1.

As of Dec. 31, 2015, mean increases of 6.0 points and 18.0 points in CHOP-INTEND scores were observed in Cohort 1 and Cohort 2, respectively.

In Cohort 1, all three patients were event-free and over 20 months of age; in Cohort 2, the first six patients  treated were event-free and older than 10.5 months of age.

AveXis’ primary focus is to develop gene therapies for SMA, initially targeting SMA type 1 and then moving to other SMA subtypes. “The past six months has been a period of significant progress for AveXis, as we completed a successful initial public offering, reported encouraging interim data for our lead program for AVXS-101 in spinal muscular atrophy (SMA) Type 1, and built an experienced leadership team,” Sean Nolan, president and chief executive officer of AveXis, said in a news release.

AveXis is planning to begin a Phase 2 trial of AVXS-101 in early 2017, and to begin a Phase 1 trial using a cerebrospinal fluid (CSF) delivery in patients with SMA type 2 later in 2016.

AVXS-101 has been granted Orphan Drug designation for the treatment of all types of SMA ,and Fast Track designation for the treatment of SMA type 1, one of the most life-threatening of neurological genetic disorders. Both designations came from the U.S. Food and Drug Administration.