AveXis Phase 1 Trial of AVXS-101 for SMA and plans for Europe

AveXis Phase 1 Trial of AVXS-101 for SMA and plans for EuropeAveXis reported topline results from the Phase 1 trial of its gene therapy product AVXS-101 for SMA Type 1. Find out how this product works here.

“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.”

The results:

This Phase 1 was 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 peri-operatively,
  • video confirmed achievement of ability to sit unassisted.
  • Exploratory objective measures were assessed, including a standard motor milestone development survey and Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND).
  • No new treatment-related safety or tolerability concerns were identified: As of 20th January 2017, AVXS-101 appeared to have a favourable safety profile and to be generally well tolerated.
  • 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 20th January 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 20th January 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 20th January 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.


“These topline data in aggregate for this Phase 1 study suggest a one-time infusion of AVXS-101 appears to be well-tolerated, with a favorable safety profile, and indicate the potential for a clinically transformative effect on event-free survival, rapid and sustained increases in motor function and achievement of motor milestones never observed in the natural history of this disease,” said Sukumar Nagendran, MD, Senior Vice President and Chief Medical Officer, AveXis.

News for trials in Europe:

  • AVXS-101 Accepted into PRIME Program: On 31st January 2017, AveXis announced the European Medicines Agency (EMA) granted access into its PRIority MEdicines (PRIME) program for AVXS-101 for the treatment of SMA Type 1. PRIME is intended to enhance support for the development of medicines – specifically those that may offer a major therapeutic advantage over existing treatments or benefit patients without treatment options – through early and proactive support by EMA to optimize the generation of robust data and development plans, and potentially expedite the assessment of the Marketing Authorisation Application so these medicines may reach patients sooner.
  • EU Pivotal Trial to Reflect Single-Arm Design: On 6th February 2017, AveXis announced the planned pivotal study of AVXS-101 in SMA Type 1 in the European Union (EU) will reflect a single-arm design, using natural history of the disease as a comparator, and will enroll approximately 30 patients. This update was based on receipt of the Scientific Advice response from the Scientific Advice Working Party within the Committee for Medicinal Products for Human Use (CHMP) of the EMA. In addition to evaluating safety, the planned pivotal trial is expected to evaluate achievement of motor milestones, specifically patients’ ability to sit unassisted, as well as an efficacy measure defined by the time from birth to an event. The CHMP additionally recommended AveXis discuss the potential for Conditional Marketing Authorisation in a future meeting with EMA.


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