AveXis Releases New Data on Phase 1 Clinical Trial

AveXis has released new data from their current Phase 1 clinical trial testing AVXS-101, a systemic delivery of gene therapy for SMA. The data from this initial trial will inform future clinical studies of gene therapy approaches.

“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,” said Sean Nolan, President and Chief Executive Officer of AveXis.

New Data Released

In January 2016, AveXis reported interim data through the December 31, 2015 time period from the ongoing Phase 1 trial of AVXS-101 in SMA Type 1. The data reported in this release reflects that same dataset and time period. AveXis reported that AVXS-101 appears to have a favorable safety profile and appears to be generally well tolerated in patients studied as of December 31, 2015. As of that date, there had been a total of 10 serious adverse events (SAEs) reported; two of these were determined to be related to therapy and involved clinically asymptomatic, elevated liver function enzymes. Both cases have resolved.

As of December 31, 2015, no patient in either dosing cohort had experienced an “event.” An event is defined as death, or until a patient requires at least 16 hours per day of ventilation support for breathing for 14 consecutive days in the absence of an acute reversible illness, or perioperatively. The median event-free age of all 15 patients was 11.8 months, with the oldest patient at 25.8 months of age. In Cohort 1, all 3 patients were over 20 months of age and event-free. In Cohort 2, the first 6 patients to be treated were greater than 10.5 months of age and event-free.

As of December 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. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) is a test developed to measure motor skills of patients with SMA Type 1, and other motor milestone development surveys and tests.

Upcoming Clinical Trials

Enrollment for this Phase 1 trial has recently been completed. AveXis plans to initiate Phase 2 trial of systemic delivery in the first half of 2017. AveXis has also announced plans for a Phase 1 trial testing a second approach, CSF delivery, in individuals with SMA type II. This trial is scheduled to begin in the second half of 2016.

Cure SMA Funds Multiple Gene Therapy Approaches

Beginning in 2010, Cure SMA made a series of grants to Nationwide Children’s Hospital to study gene therapy, also called gene transfer. Spinal muscular atrophy (SMA) is caused by a mutation in the survival motor neuron 1 gene (SMN1). Because of this mutation, the individual does not produce enough survival motor neuron (SMN) protein.

Gene transfer may increase SMN levels by using a virus, called a vector, to deliver the SMN1 gene to affected cells. Dr. Brian Kaspar and Dr. Mendell discovered that Adeno-associated virus serotype 9 (AAV9) had the unique ability to cross the blood brain barrier and the Blood-Cerebrospinal Fluid Barrier (CSF).

Currently, two approaches are being studied: an injection into a vein, known as systemic delivery, which is the process being tested in this current trial, and delivery directly into the cerebrospinal spinal fluid (CSF), a process known as CSF-delivered gene therapy. CSF-delivered gene therapy has shown promise for reducing the amount of drug required for larger and older patients. This could eventually make the treatment accessible to a wider population.

In total, Cure SMA has granted $845,000 for gene therapy, including support for both the systemic program and the CSF program. Using the data generated with our funding for CSF delivery, Dr. Kaspar and his team were able to secure a $4 million grant from NINDS in 2013, to develop this delivery approach for human clinical trials in SMA.

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