Novartis revives inclisiran U.S. filing by sidestepping FDA's manufacturing inspection concerns

Novartis headquarters
Novartis has refiled blockbuster-to-be PCSK9 cholesterol drug Leqvio, also known as inclisiran, with the FDA. (Novartis)

Novartis is trying to set heart drug Leqvio back on its course to blockbuster land after a shocking FDA rejection late last year. Instead of risking a further delay by dwelling on making changes at a third-party facility, Novartis is taking matters into its own hands.

The company has refiled Leqvio, or inclisiran, to the FDA with a new manufacturing location, Novartis said Tuesday.

In December, the FDA rejected the drug thanks to what Novartis previously called “unresolved facility inspection-related conditions.” Now, the company is shifting finished drug production of the PCSK9 med from an Italian plant run by contractor Corden Pharma to its in-house facility in Schaftenau, Austria.

Novartis started the tech transfer to the Austria site before the FDA rebuff, the drugmaker said Tuesday. The company had completed the process by April, CEO Vas Narasimhan said at the time.

Despite the FDA rejection, the drug won EU clearance in December with the Italian facility serving as its manufacturing factory. The FDA had to rely on a paper-based inspection of the site because of pandemic restrictions.

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Leqvio was the centerpiece of Novartis’ $9.7 billion acquisition of The Medicines Company in 2019. At the time, the company hoped the late-stage prospect could quickly generate meaningful sales.

But industry watchers had expressed concerns about the drug’s value even before the regulatory hiccup. Fellow antibody drugs targeting PCSK9—Amgen’s Repatha and Sanofi and Regeneron’s Praluent—have yet to live up to their blockbuster expectations thanks to a pricing fight. 

Aside from the inspection-related rejection, the pandemic has also had an effect on an important trial for the drug. Novartis has pushed back the readout for the key cardiovascular outcomes trial, dubbed ORION-4, to 2026 from 2024 as the pandemic slowed patient recruitment in the U.K., Novartis Chief Medical Officer John Tsai, M.D., said in April.

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Right now, Leqvio only has data showing it can lower bad cholesterol levels. But the real goal, as both Repatha and Praluent have demonstrated, is to reduce dangerous cardiovascular events such as heart attack and stroke.

Novartis launched Leqvio in Germany and Austria in February in patients at very high cardiovascular risk, Novartis’ pharma chief Marie-France Tschudin said on an April conference call. The company is also rolling out the drug in the U.K. with help of a “population-level agreement” with NHS England. Without the outcomes data, the company was discussing similar access deals with EU countries, she added.

An anticipated major growth driver for Novartis, Leqvio could reach $2 billion in 2026 sales, EvaluatePharma recently predicted.