The U.S. Food and Drug Administration approved AveXis’ Zolgensma, the first gene therapy to treat children less than two years of age with the most severe form of spinal muscular atrophy (SMA), and a leading genetic cause of infant death.

The Novartis subsidiary priced a one-time infusion of Zolgensma at $2.12 million, which it said is based at a 50 percent discount to the average genetic pediatric ultra-rare disease therapy of $4 million to $5 million over ten years. Novartis’ is working with payers to create five-year outcomes-based agreements and a pay-over-time option to pay for the gene therapy over five years.

If Novartis’ pricing scheme is successful, it will set a bar for other gene therapies that are in the pipeline for approval. It also becomes strong competition for Biogen’s Spinraza, approved to treat SMA in late 2016, and marketed at $750,000 for the first year, and $375,000 annually afterwards.

SMA is a rare genetic disease caused by a mutation in the SMN1 gene, which encodes the protein critical for the maintenance and function of specialized nerve cells called motor neurons. If there is not enough functional SMN protein, then the motor neurons die, leading to debilitating and often fatal muscle weakness. Infantile-onset SMA is the most severe and most common subtype of SMA. Children with this condition have problems holding their head up, swallowing and breathing. These symptoms may be present at birth or may present by the age of six months.

Zolgensma is a one-and-done gene therapy designed to address the genetic root cause of spinal muscular atrophy by providing a functional copy of the human SMN gene to halt disease progression through sustained SMN protein expression. It is approved to treat patients with bi-allelic mutations in the survival motor neuron 1 (SMN1) gene. It is also approved to treat infants who are pre-symptomatic at diagnosis.

“A diagnosis of SMA is devastating, leaving untreated babies who have the most severe form with painfully short, highly medicalized lives, during which they are unable to lift their heads, sit or roll, have difficulty swallowing and breathing and need 24-hour care,” said Jerry Mendell, principal investigator at the Center for Gene Therapy at The Abigail Wexner Research Institute of Nationwide Children’s Hospital in Columbus, Ohio. “In the START clinical trial we conducted with Zolgensma, all children were alive at the conclusion of the study and many were able to sit, roll, crawl, play, and some could walk. This level of efficacy, delivered as a single, one-time therapy, is truly remarkable and provides a level of unprecedented hope for families battling SMA Type 1. We now have data four years out from the trial, and we see the durability of this gene therapy.”

Zolgensma was approved based on data from the ongoing phase 3 STR1VE trial and the completed Phase 1 START trial evaluating the efficacy and safety of a one-time IV infusion of Zolgensma in patients with SMA Type 1 who showed symptoms of SMA at less than six months of age, with one or two copies in the STR1VE trial or two copies in the START trial of the SMN2 backup gene and who have bi-allelic SMN1 gene deletion or point mutations. The data show Zolgensma provides rates of survival never seen in the natural history of the disease; rapid motor function improvement, often within one month of dosing; and, durable milestone achievement, including the ability to sit without support, a milestone never achieved in untreated patients. Safety observations in STR1VE were comparable to those seen in the START trial. The most commonly observed adverse events were elevated levels of the liver enzyme aminotransferases and vomiting.

Photo: Jerry Mendell, principal investigator at the Center for Gene Therapy at The Abigail Wexner Research Institute of Nationwide Children’s Hospital in Columbus, Ohio

X