Novartis beefs up its case for Zolgensma gene therapy ahead of FDA decision

Novartis is expecting the FDA to decide on its spinal muscular atrophy (SMA) gene therapy next month, but it’s already padding its case with new phase 3 data. And it's data one executive hopes will quell some concerns raised about the therapy.

For one thing, the numbers help address questions about whether the SMA treatment, dubbed Zolgensma, has been tested in enough patients to truly assess its efficacy.

All but one of the 22 SMA patients treated in a phase 3 trial of Zolgensma were alive and had not suffered serious complications as of the end of September, Novartis said Tuesday. Normally, half of babies with the form of SMA that Zolgensma treats either die or require ventilation within their first year of life, Novartis said. The median age of the trial patients was 9.5 months. Plus, several of the children reached developmental milestones that are rare among babies with SMA, including holding their heads up and sitting.

More than 150 patients have been treated with Zolgensma so far—a significant milestone, said Brian Kaspar, Ph.D., chief scientific officer of AveXis, the Novartis unit that developed the gene therapy.

“We get a lot of questions about AveXis only having treated 15 patients,” Kaspar said in an interview, referring to the fact that the FDA launched its Zolgensma review based on a 15-patient trial. “But it’s a broad, global clinical trial program. We’re really gratified to see the prolonged event-free survival in these patients with rapid increases in their motor functional abilities and achievements.”

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SMA is caused by a defect in the SMN1 gene, which makes a protein critical to the survival of motor neurons, and Zolgensma is a one-time therapy meant to replace that gene.

The trial helped AveXis’ scientists to better understand how Zolgensma works, because they could examine tissues from the one patient who did not survive, Kaspar said. That analysis showed the gene therapy had restored expression of the SMN protein, and levels of the protein were comparable to those found in people who don’t suffer from the disease, the company said.

“We never had an understanding of whether [Zolgensma] was targeting motor neurons as effectively as we thought it would,” Kaspar told FiercePharma. “This was an opportunity for us to be able to look at the safety of the product in every single organ. Secondly, it allowed us to confirm that we’re targeting neurons and cells in the brain and spinal cord.”

Researchers found no signs that Zolgensma affected peripheral organs, and an independent safety investigation determined the patient’s death was not related to the treatment, Novartis said.

Only one other patient who has received the gene therapy has died, a spokesperson for Novartis told FiercePharma. That patient died during a European trial, and it was attributed to a respiratory infection and neurological complications. A trial investigator said the death might have been treatment-related, but autopsy results are pending. The company has shared the details with regulatory authorities, the spokesperson said.

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If Zolgensma is approved, it could be launched before the second half of this year, analysts at Clarivate predicted in a report last month. The treatment could bring in $449 million in sales this year, helped by a simultaneous launch in Japan, Clarivate said, projecting $2 billion in annual sales by 2023.

That’s assuming payers get on board with the cost, of course, and Zolgensma is expected to bear a very high price tag. Novartis hasn’t announced its pricing plans for Zolgensma yet, but Dave Lennon, president of AveXis, created a stir last year when he suggested it would be cost-effective at a price of $4 million to $5 million.

Wall Street analysts are betting the price will end up closer to $2 million, but even that figure has kicked up some controversy. Earlier this month, the Institute for Clinical and Economic Research (ICER) said that, based on its analysis, a Zolgensma price of $900,000 or less would make the most sense from a cost-effectiveness standpoint.