Novartis' Zolgensma expansion hits FDA roadblock, giving Biogen and Roche a reprieve

Novartis was gunning for an FDA application in 2021 for a new formulation of Zolgensma, aiming to bring its gene therapy to older spinal muscular atrophy patients with the help of new animal safety data. That hope has now been dashed.

Rather than accept a filing based on a phase 1/2 trial, the FDA will require Novartis to run a pivotal phase 3 study of a Zolgensma formulation infused into the spinal fluid, rather than intravenously, the Swiss pharma said Wednesday.

While the FDA-approved IV version of the gene therapy is allowed in children under the age of 2, Novartis hopes the intrathecal version could reach patients up to 5 years old. The FDA’s recommendation could push the filing to at least 2023.

The delay is good news for two Zolgensma rivals—Biogen’s Spinraza and Roche’s newly approved Evrysdi—analysts said in investor notes Wednesday.

Novartis’ intrathecal Zolgensma has already faced bumps in the road to FDA review. Last fall, the agency halted enrollment in the high-dose arm of the drug’s phase 1/2 Strong trial after preclinical tests flagged a safety problem related to spinal-cord inflammation and neuronal cell degeneration.

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After that, Novartis decided to produce one-year monkey data so that “we’ll have the best possible data” to support a filing in 2021, CEO Vas Narasimhan said during a conference call in July. Turns out, those additional data wouldn’t be enough by FDA standards.

The FDA’s request for an additional clinical study isn’t related to the partial clinical hold on the Strong study, Novartis said. A phase 3 won’t start in the U.S. until the FDA lifts that hold, the company said. It didn’t specify a potential design or length for the confirmatory study.

The delay is a clear setback for Novartis; the intrathecal version makes up $1 billion of Zolgensma’s total $2.8 billion worldwide peak sales estimate, Jefferies analyst Peter Welford figures.

Instead, it offers some relief to Biogen’s first-to-market Spinraza and Roche’s up-and-coming Evrysdi, both of which are approved across age groups and SMA subtypes.

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SVB Leerink analyst Mani Foroohar recently predicted that Evrysdi could steal meaningful share from Spinraza because of its broad label, convenient oral dosing and low price tag. As for Zolgensma, the potential of a cure with a one-time gene therapy could lure some patients away from those chronic treatment options—if it gets an approval in the target patient population.

Now, with a Zolgensma approval in older patients further away, Spinraza has more breathing room—and a better chance to focus on competition from Evrysdi. And Roche has a longer runway to establish Evrysdi in the market.

During an investor event last week, Teresa Graham, Roche’s head of pharma global product strategy, said about two-thirds of Evrysdi patients have prior experience with Spinraza or Zolgensma. Welford currently forecasts $2.4 billion for Evrysdi peak sales.