Novartis reports positive interim Phase III data for Zolgensma gene therapy candidate in SMA type 1

Novartis' AveXis unit on Tuesday said interim data from the Phase III STR1VE trial presented at the Muscular Dystrophy Association (MDA) conference demonstrated that Zolgensma (onasemnogene abeparvovec-xioi) prolonged event-free survival in patients with spinal muscular atrophy (SMA) type 1. It also said the investigational gene therapy, formerly known as AVXS-101, led to an early and rapid increase in motor function and showed a significant milestone achievement compared to untreated natural history.

The findings "reinforce what was seen in the pivotal Phase I START trial, including trends toward prolonged survival and milestone achievement never seen in the natural history of the untreated disease," remarked chief medical officer Olga Santiago. "With a patient population and baseline characteristics closely matched to the START trial, these data build upon the body of evidence supporting the use of Zolgensma for SMA type 1," she added.

The STR1VE trial included 22 patients who carry at least one copy of the SMN2 backup gene and who have bi-allelic SMN1 gene deletion or point mutations. "These criteria are well-matched to the patient population that was enrolled in the…START trial, while potentially providing treatment to some of the rarer subpopulations on an exploratory basis," Novartis said. The participants, who were under six months of age at the time of gene therapy, received a single intravenous infusion of Zolgensma.

The company reported that 21 patients were alive and event-free as of September 27 last year, with an event defined as either death or at least 16 hours a day of breathing ventilation support for 14 consecutive days. The median age at the time of analysis was 9.5 months, "with six of seven patients who could have reached 10.5 months of age or older surviving event-free," Novartis said. Untreated natural history indicates that 50 percent of babies with SMA type 1 die or require permanent ventilation by the time they reach 10.5 months of age, the company noted.

In other results, Novartis said the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score rose by an average 7 points at one month after gene transfer and 11.8 points after three months, "reflecting improvement in motor function from baseline." In addition, the number of patients who could hold their heads erect for at least three seconds without support rose from 12 in September 2018 to 17 by the end of December, while the number of children who could turn from back to both the right and left sides increased from three to seven over the same period.

The company also reported that the first-in-human analysis of tissues from the deceased patient showed that Zolgensma successfully transduced tissues of the central nervous system, including brain and spinal cord motor neurons, and also showed "widespread expression of SMN comparable to tissue from an unaffected individual." The ongoing STR1VE trial is projected to complete in 2020.

Meanwhile, the FDA is evaluating Zolgensma under a priority review, with a decision expected in May. Novartis also anticipates regulatory authorisation of the drug in Europe and Japan this year.

Earlier this month, the Institute for Clinical and Economic Review (ICER) issued a final report calling on Novartis to price Zolgensma below the company's hypothetical value of $4 million to $5 million. ICER had previously suggested that the gene therapy could be more cost-effective than Biogen and Ionis Pharmaceuticals' SMA treatment Spinraza (nusinersen) once additional data about its price and success rates are available.

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