AveXis Reports Results from Phase 1 Trial of AVXS-101

AveXis, Inc., a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, today reported topline results from the Phase 1 trial of AVXS-101 in spinal muscular atrophy (SMA) Type 1. The company also reported financial results for the fourth quarter and full year ended December 31, 2016, recent corporate highlights and upcoming milestones.

“The completion of our Phase 1 clinical study of AVXS-101, the first ever gene therapy studied for the treatment of SMA Type 1, is an exciting and eagerly awaited milestone, and we are quite pleased with these data,” said Sean Nolan, President and Chief Executive Officer of AveXis. “The past few months have been productive for AveXis, and we look forward to continuing the momentum with several upcoming corporate catalysts, including the planned Type B CMC meeting with the FDA, as well as ongoing collaborative discussions with regulatory authorities in the United States and Europe to explore the most expeditious pathways for marketing approval of AVXS-101.”

Topline Results from the Phase 1 Trial of AVXS-101 in SMA Type 1

  • No New Treatment-related Safety or Tolerability Concerns Identified: As of January 20, 2017, AVXS-101 appeared to have a favorable safety profile and to be generally well tolerated, with no new safety or tolerability concerns identified. 
  • No New Events and 15 of 15 Patients Event-Free at 13.6 Months, including 12 of 12 Patients in Proposed Therapeutic-Dose Cohort: As of January 20, 2017, 12 of 12 patients (100%) in the cohort of patients who received the proposed one-time therapeutic dose of AVXS-101 (Cohort 2) had reached 13.6 months of age event-free, where the expected event-free survival rate based on natural history of the disease is 25%. The median age at last follow-up for Cohort 2 was 20.2 months, with the oldest patient at 31.1 months of age. 
  • Rapid and Sustained CHOP INTEND Improvements Above Baseline: As of January 20, 2017, mean increases from baseline in CHOP INTEND scores of 7.7 points in Cohort 1 and 24.7 points in Cohort 2 were observed, reflecting improvement in motor function. In Cohort 2 there were mean increases in CHOP INTEND of 9.8 points one month after gene therapy and 15.4 points three months following gene therapy. 
  • Cohort 2 Patients Consistently Achieved and Maintained Key Developmental Motor Milestones: As of January 20, 2017, 11 of 12 patients (92%) in Cohort 2 achieved head control, nine of 12 patients (75%) could roll a minimum of 180 degrees from back to both left and right, and 11 of 12 patients (92%) could sit with assistance. For the end-of-study assessment, AveXis evaluated three validated and well-established measures of sitting unassisted for periods of increasing duration. Nine of 12 patients (75%) could sit unassisted for at least five seconds, seven of 12 patients (58%) could sit unassisted for at least 10 seconds and five of 12 patients (42%) could sit unassisted for 30 seconds or more. Two patients could walk independently, and each had achieved earlier and important developmental milestones such as standing with support, standing alone and walking with support.

Upcoming Clinical Trials of AVXS-101 in SMA Type 1

AveXis is planning to initiate two new clinical trials in the first half of 2017:

  • A single-arm, Phase 3 trial testing systemic delivery of AVXS-101 in infants with SMA type 1—the same delivery method being tested in the current trial 
  • A Phase 1 trial testing CSF-delivery (intrathecal injection) in children with SMA type 2.

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, 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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