The death of an infant in a clinical trial of Novartis’ gene therapy for spinal muscular atrophy Type 1 was not related to the therapy, a subsidiary of the Swiss drugmaker said Thursday.

AveXis, which originally developed the gene therapy Zolgensma (onasemnogene abeparvovec-xioi), is presenting interim data from Phase III studies, SPR1NT and STR1VE, and long-term follow-up data from the Phase I START study, at the European Paediatric Neurology Society’s annual congress in Athens, which started Tuesday and lasts through Saturday.

As part of the announcement, AveXis said that according to a coroner’s report, the previously reported death of an infant in the STR1VE-EU study from hypoxic-ischemic brain damage stemming from a respiratory tract infection – which itself resulted from SMA Type 1 – was not related to Zolgensma. The infant’s death had been reported in April, and at the time the clinical trial investigator who administered the therapy had deemed it possibly related to treatment.

The Food and Drug Administration approved Zolgensma in May. Novartis acquired AveXis last year for $8.7 billion. Zolgensma carries a list price of more than $2 million, though third-party drug-pricing watchdog the Institute for Clinical and Economic Review has stated that the price – for a potentially curative therapy – meets cost-effectiveness thresholds.

Another approved treatment for SMA is Biogen’s Spinraza (nusinersen), which is taken throughout the patient’s life. Biogen said Wednesday that it would launch a new clinical trial to see if a higher dose of the drug can provide greater efficacy across a broad patient population.

SMA is a rare, genetic disease that causes muscular weakness and wasting that usually becomes worse with age, according to the National Institutes of Health. SMA Type 1 is the most common form, and most children with it do not survive past early childhood due to respiratory failure. Type 2 is less severe, though still life-threatening, with patients usually living into their 20s or 30s. Type 0 is the rarest and most severe kind, and patients with it often die in infancy.

According to STR1VE clinical program data as of the May 31 cutoff, – which includes studies in Europe, the U.S. and Asia-Pacific – patients treated with Zolgensma have continued to gain motor milestones. Half of those in STR1VE-US and 6 percent in STRIVE-EU achieved the ability to sit for at least 30 seconds without support, which babies with SMA Type 1 are unable to do. Meanwhile 83 percent of the six patients in STR1VE-US who reached 18 months of age were able to sit independently for 30 seconds, while one patient could pull to a stand and walk with assistance.

SPR1NT is investigating Zolgensma in pre-symptomatic patients with SMA who have two or three copies of the SMN2 gene and are less than 6 weeks of age. All 10 patients with two copies of the gene achieved a Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders score greater than 50, with five reaching the maximum score of 64. Sixty percent of those patients were able to sit without support for at least 30 seconds, while 30 percent could stand with assistance.

In START, all 12 patients who had received the targeted therapy dose were alive at the close of the 24-month study, and all 10 who had enrolled in the study’s long-term follow-up were alive as of May 31, with a mean age of 4.2 years. Seven were not receiving concomitant therapy with Spinraza, and six were not receiving respiratory support.

Zolgensma became the subject of a scandal last month when the FDA revealed that some of the preclinical data had been manipulated, and that AveXis had learned about the issue in March of this year, but did not inform the FDA until late June, after Zolgensma was approved. Novartis has sought to explain the time lag by stating that it wanted to complete a full investigation before disclosing the issue to the FDA. Two of AveXis’ key scientists, brothers Brian and Allan Kaspar, were reportedly ousted from the company over the scandal.

Photo: jxfzsy, Getty Images

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