Positive Pulmonary Data from Phase 1 Trial of SMA Type 1 Gene Therapy Presented by AveXis

Margarida Azevedo, MSc avatar

by Margarida Azevedo, MSc |

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Phase 1 trial of SMA gene therapy

AveXis presented positive pulmonary data from an interim analysis of its ongoing Phase 1 trial of AVXS-101 for the treatment of spinal muscular atrophy (SMA) type 1. The presentation, by Richard Shell, M.D., a member of the Section of Pulmonary Medicine at Nationwide Children’s Hospital, was made at the recent 2016 International Conference of the American Thoracic Society in San Francisco.

The clinical trial enrolled 15 patients diagnosed before they were 6 months old, with two copies of the SMN2 backup gene. Primary outcomes were defined as safety and tolerability, and a secondary outcome measure was efficacy, defined as time from birth to an “event,” either death or the need for at least 16 hours a day of ventilation support for 14 consecutive days.

Exploratory outcome measures included motor function testing, assessed by several motor milestone surveys and tests, including the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) developed to measure motor skills in people with SMA type 1. Patients were divided in two cohorts: 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).

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. Moreover, 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 company recently released other positive interim analyses data showing the therapy had a favorable safety and tolerability profile.

“The preliminary data appear to indicate AVXS-101 may have a positive impact on the pulmonary outcomes of patients in the trial suffering from SMA Type 1, which may be impacting the overall survival benefit,” said Suku Nagendran, M.D., AveXis senior vice president and chief medical officer, in a news release. “We look forward to reviewing the ongoing data from this study over the coming year as we continue the development of AVXS-101.”

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.