SMA Type 1 Treatment Candidate Granted FDA Breakthrough Therapy Designation

Ana de Barros, PhD avatar

by Ana de Barros, PhD |

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The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to AVXS-101, AveXis’ lead development candidate to treat spinal muscular atrophy (SMA) Type 1 in pediatric patients.

AVXS-101 is a proprietary gene therapy candidate of a one-time, intravenous treatment for SMA Type 1, and, according to AveXis, is the only clinical-stage gene therapy in development for SMA.

According to AveXis, Breakthrough Therapy Designation provides easier access to FDA managers so the agency can provide advice on generating the evidence needed for approval of the therapy, with “guidance on an efficient drug development program, an organizational commitment involving FDA’s senior managers, and eligibility for rolling review and priority review.”

The FDA’s Breakthrough Therapy status was based on preliminary results from an ongoing study conducted in partnership with The Ohio State University and The Research Institute at Nationwide Children’s Hospital.

The open-label study is designed to evaluate the safety and efficacy of AVXS-101 in patients suffering from SMA Type 1. Fifteen patients were enrolled who had been diagnosed before they were 6 months old, with two copies of the SMN2 backup gene. The patients were divided into two groups: three babies, ages 6 to 7 months at time of dosing, received a low dose of 6.7 x 10^13 vg/kg (cohort 1), while the remaining 12 babies, ages 1 to 8 months at time of dosing, received 2.0 x 10^14 vg/kg (cohort 2).

The primary study outcome is safety and tolerability and the secondary outcome is an efficacy measure as defined by the time from birth to an “event” (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 perioperatively).

Exploratory outcome measures include muscle assessment studies measured by a patient’s CHOP-INTEND score, a reliable measure of motor skills in patients with SMA-I.

Based on the pulmonary data assessed during the analysis, gene therapy appeared to improve patients’ pulmonary function, reducing the need for ventilation support and allowing patients to recover from the respiratory illnesses that often lead to premature death of SMA Type 1 patients.

According to the data, as of April 1, 2016, none of the patients in either treatment cohort required permanent ventilation. Also, 80 percent (8 out of 10) of patients receiving the therapeutic dose of 2.0×1014 vg/kg who did not need biphasic/bi-level ventilation (BiPAP) support prior to gene therapy continued with no ventilation support.

The FDA has asked AveXis to submit a Type B reunion request for a multidisciplinary, comprehensive debate of AVX-101 clinical development program. The company plans to submit a request later this month.

“We are encouraged to have received Breakthrough Therapy Designation for AVXS-101, and look forward to collaborating with the FDA to determine next steps in the development pathway for AVXS-101,” AveXis President and CEO Sean P. Nolan said in a press release. “By this action the FDA recognizes the high unmet need for effective treatment options for patients suffering from SMA.”