FDA Approves Gene Therapy With $2.1M Price Tag for Spinal Muscular Atrophy in Pediatric Patients

Another gene therapy will soon hit the market with the FDA’s approval of onasemnogene abeparvovec-xioi (Zolgensma), the first approved gene therapy for the treatment of children under age 2 with spinal muscular atrophy (SMA) and the most expensive treatment to ever hit the market.

With a $2.1 million price tag, AveXis—a Novartis company—announced that it will work with payers to implement 5-year outcomes-based agreements and novel pay-over-time options. The company also said it will offer a patient program to support affordability and access.

“Zolgensma is a historic advance for the treatment of SMA and a landmark 1-time gene therapy. Our goal is to ensure broad patient access to this transformational medicine and to share value with the healthcare system,” said Vas Narasimhan, chief executive officer of Novartis, in a statement.

According to Narasimhan, the company used value-based pricing frameworks to price the therapy at approximately 50% less than several established benchmarks, including the 10-year current cost of chronic SMA therapy. When updated for its full labeled indications, Narasimhan expects the therapy to be within the range of cost-effectiveness thresholds set by the Institute for Clinical and Economic Review.

SMA is an inherited rare disease caused by a mutation in the survival motor neuron 1 gene, which encodes the survival motor neuron (SMN) protein—a protein found throughout the body that is critical for maintenance and function of motor neurons. Without enough functional SMN protein, motor neurons die, resulting in debilitating and often fatal muscle weakness.

“Children with SMA experience difficulty performing essential functions of life. Most children with this disease do not survive past early childhood due to respiratory failure,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement. “Patients with SMA now have another treatment option to minimize the progression of SMA and improve survival.”

The safety and efficacy of onasemnogene abeparvovec-xioi has been demonstrated throughout the ongoing STR1VE clinical trial, as well as the completed START clinical trial. None of the 21 patients enrolled in the STR1VE trial required noninvasive ventilator support, and all patients could feed orally before treatment. As of the March 2019 data cutoff, 19 patients were alive without permanent ventilation and were continuing in the trial. Ten patients (47.6%) experienced improvement in ability to reach developmental motor milestones, such as head control and the ability to sit without support.

In the START trial of 15 patients, all 12 patients in the high-dose cohort were alive without permanent ventilation and 1 patient in the low-dose cohort was on permanent ventilation at 24 months. No patients in the low-dose cohort were able to sit without support, sit, or walk. Meanwhile, 9 of the 12 patients in the high-dose cohort were able to sit without support for 30 seconds, and 2 patients were able to stand and walk without assistance, suggesting a dose-response relationship.

The most common adverse events associated with onasemnogene abeparvovec-xioi include elevated liver enzymes and vomiting. The treatment comes with a boxed warning that acute serious liver injury can occur.