AveXis Reports Data from Ongoing Phase 1 Trial of AVXS-101 in Spinal Muscular Atrophy Type 1

Today, AveXis, Inc. presented an interim analysis of data as of April 1, 2016 from the ongoing Phase 1 trial of AVXS-101 for the treatment of spinal muscular atrophy (SMA) Type 1. Jerry Mendell, MD, director of the Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital, presented the data at the 19th Annual Meeting of the American Society of Gene & Cell Therapy in Washington, D.C.

The data reported at the meeting show that AVXS-101 continues to demonstrate a favorable safety profile in patients studied, with no new treatment-related safety or tolerability concerns identified; all patients in both the low-dose and proposed therapeutic-dose cohorts remain without an “event”. Events are 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 mean motor function score continues to increase, with two patients having achieved motor function in a range considered to be normal.

Dr. Mendell said, “Given the rapid and devastating disease course of SMA Type 1, it is very encouraging to see that all patients in both dosing cohorts have remained event free, and all patients have demonstrated sustained improvements above baseline in motor function since receiving AVXS-101.

The ongoing Phase 1 study is designed to evaluate safety and preliminary indications of efficacy of AVXS-101 in patients suffering from SMA Type 1. Data as of April 1, 2016 has shown:

  • AVXS-101 appears to have a favorable safety profile and to be generally well tolerated in patients studied.
  • No patients in either dosing cohort have experienced an “event.” The median event-free age of all 15 patients was 14.9 months, and the median event-free age of patients in Cohort 1 was 25.7 months and in Cohort 2 was 11.7 months.
  • Mean increases of 8.7 points and 19.2 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.
  • The natural history of SMA Type 1 indicates that bulbar weakness leads to impaired swallowing, malnutrition and growth failure. The median age to growth failure is 7 months of age2. The median age to nutritional support is 8 months of age (IQR 6-13 months)1. AVXS reported today that 7 of 7 (100%) of AVXS-101 patients that did not require feeding support before treatment continued without feeding support as of April 1, 2016 in the ongoing Phase 1 trial. Five patients had gastric feeding tube placement prior to gene therapy.
  • The natural history of SMA Type 1 indicates that bulbar muscle weakness, skeletal muscle weakness in the neck and intercostal muscle weakness lead to respiratory impairment, poor clearance of airway secretions, risk of aspiration and recurrent infections leading to death or permanent ventilation. The median age to permanent ventilation or death is 10.5 months (IQR 8.1-13.6 months), and by 13.6 months only 25 percent of SMA Type 1 patients are alive and free of permanent ventilation1. In the ongoing trial, 8 of 10 (80%) of AVXS-101 patients that did not use biphasic/bi-level ventilation (BiPAP) support before gene transfer continue without any ventilation support as of April 1, 2016 (the 2 exceptions being after severe illness/hospitalizations to assist recovery).

“We are encouraged by these interim results as we work diligently to bring AVXS -101 to patients who suffer from SMA Type 1, a devastating disease for which there are currently no FDA-approved therapies,” said Suku Nagendran, MD, Senior Vice President and Chief Medical Officer, AveXis. “We look forward to reviewing the ongoing data from this study over the coming year as we continue the development of AVXS-101.”

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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