Rare Daily Staff

Spinal muscular atrophy type 1 patients in an early-stage clinical trial of AveXis’ gene therapy were alive and event free at 20 months of age, according to a report in the New England Journal of Medicine.

A natural history of the disease indicates that only eight percent of untreated patients with SMA Type 1 will survive event-free at 20 months of age, the company said.

SMA is a severe neuromuscular disease characterized by the loss of motor neurons leading to progressive muscle weakness and paralysis. It is caused by a genetic defect in the SMN1 gene that codes SMN, a protein necessary for survival of motor neurons. The most severe form of SMA is type 1, a lethal genetic disorder characterized by motor neuron loss and associated muscle deterioration, which results in mortality or the need for permanent ventilation support before the age of two for greater than 90 percent of patients.

“It is incredibly encouraging to see that all children who have received AVXS-101 remain event-free and demonstrate a durable treatment effect at 20 months of age and older, including in many cases achievement of new developmental milestones,” said Sean Nolan, president and CEO of AveXis. “To have these phase 1 data published in the prestigious New England Journal of Medicine highlights the groundbreaking work of Dr. Jerry Mendell and his team and further validates the clinically transformative nature of gene therapy in children with SMA type 1.”

The publication provides detailed data as of August 7, 2017, from the phase 1, open-label, dose-escalating study, 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 perioperatively, and video confirmed achievement of ability to sit unassisted.

AVXS-101 appeared to have a favorable safety profile and to be generally well tolerated, with no new treatment-related safety or tolerability concerns identified. A total of five adverse events in four patients were deemed treatment-related. Of these, two were serious adverse events experienced by two patients, and three were non-serious adverse events experienced by two patients. All consisted of clinically asymptomatic liver enzyme elevations and were resolved with prednisolone treatment. There were no clinically significant elevations of gamma-glutamyl transferase, alkaline phosphatase, or bilirubin. Other non-treatment-related adverse events were expected and were associated with SMA.

Several exploratory objective measures were assessed, including a standard motor milestone development survey. Patients in a cohort that received a therapeutic dose showed a positive response. As of August 7, 11 of 12 of the patients in that cohort achieved head control, could roll over and sit with assistance, and site unassisted for at least five seconds. Two patients could crawl, pull to a stand, and stand and walk independently.

According to natural history of the disease, nearly all Type 1 patients require nutritional and respiratory support by 12 months of age, and are not able to swallow or speak effectively. As of August 7, 2017, patients who were free of respiratory or feeding support on January 20, 2017, continued without the need for supportive care. Eleven of 12 patients were able to speak.

AVXS-101 is currently being evaluated in a pivotal trial for the treatment of SMA Type 1.

November 2, 2017

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