- Novartis has to run a new clinical trial before it can seek U.S. approval for an experimental formulation of its spinal muscular atrophy gene therapy Zolgensma, the Swiss drugmaker said Wednesday, in the latest setback to its plans to treat older patients with the neuromuscular disease.
- The Food and Drug Administration requested the study to support findings from Novartis' STRONG trial, which tested an "intrathecal," or spinal injection, version of Zolgensma in older children with SMA. But Novartis can't start the new trial in the U.S. until the FDA lifts a clinical hold on the study, which was partially suspended last year due to inflammatory responses seen in animal tests.
- The intravenous form of Zolgensma is cleared for SMA patients under two years of age, when the rare disease can be most deadly. The intrathecal version is critical to Novartis' ambitions to treat older patients whose disease is less severe. Novartis aimed to submit an approval application next year.
Zolgensma's approval was a notable milestone, making it both the second gene therapy approved in the U.S., and the second treatment for SMA, a potentially deadly disease for which no medicines existed until four years ago.
But it's been a bumpy ride for Novartis since that 2019 approval. The FDA charged the company of manipulating preclinical data supporting its original application, a controversy that led Novartis to fire some top scientists and shake up its quality control operations. (The agency opted against sanctioning Novartis, however.)
And the drugmaker has now faced multiple delays in its effort to broaden the reach of Zolgensma beyond newborns and young infants.
That effort is crucial to the commercial prospects of Zolgensma. While SMA diagnosed in infancy, known as Type 1, is the most deadly, more people are living with the less severe forms of the disease. The nonprofit SMA foundation, for instance, estimates 88% of patients living with the disease have either Type 2 or Type 3, which can either stop people from walking or rob them of that ability later on.
Younger SMA patients need the muscle-boosting protein Zolgensma helps create to be expressed throughout the body, while older patients require a more targeted approach, which is why Novartis is developing the intrathecal version for them.
Currently, intravenous Zolgensma is approved in the U.S. and Japan for patients under two, and in Europe for children who weigh up to 21 kilograms. By comparison, Biogen's Spinraza and recently, Roche's Evrysdi are approved for much wider groups of SMA patients.
The intrathecal dose of Zolgensma is meant to even that playing field, though it may now be a few years until Novartis can bring that version to market.
The FDA initially halted testing of the intrathecal formulation in October, citing safety concerns from an animal study. That test is still on hold, but even when it restarts, Novartis will need more time to complete the new trial requested by the FDA. The company said the two developments are unrelated.
Novartis is discussing the details of the trial with the agency and said it will give a "comprehensive update" on its SMA program in the future. The pharma had been planning an approval submission next year, but Jefferies analyst Peter Welford now predicts that won't occur until at least 2023.
The delay boosts Roche's and Biogen's drugs, delaying would-be competition in older SMA patients. Novartis noted it's developing a similar type of drug to Roche's Evrysdi that's taken once a week orally.
Some 600 patients have been treated with Zolgensma through clinical trials, expanded access programs and commercially.
News of the FDA's request sent shares of gene therapy developer Regenxbio, which holds royalty rights to Zolgensma, down by as much as 9% Wednesday morning.