Novartis awaiting Italian plant inspection for FDA’s Leqvio decision

Novartis is confident of maintaining a December 2020 action date for its high cholesterol siRNA therapy Leqvio despite common COVID-related regulatory delays of three to five months.

Earlier this month, Novartis received positive opinion from the European Medicines Agency (EMA) for Leqvio (inclisiran), a small interfering RNA (siRNA) therapy for the treatment of adults with hypercholesterolemia or mixed dyslipidemia.

The Swiss pharma giant is hoping for the same in the US, with a PDUFA date set for December 31 2020 by the US Food and Drug Administration (FDA).

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But during a conference call discussing third quarter results, Novartis admitted the COVID-19 pandemic is delaying regulatory work, which could lead to a pushback on the decision.

“We are seeing on select instances delays due to COVID, and those COVID delays typically are in the range of three to five months,” CEO Vas Narasimham told investors. “We’re transparently reflecting that in our documentation to all of you so you can see where we are, but overall I think relatively speaking, our portfolio has remained resilient and largely on track, despite the massive disruptions of COVID all around the world.”

Specifically for Leqvio, he said Novartis has completed nearly all the documentation required by the FDA including a full clinical review but must now await a regulatory inspection.

“The only outstanding item now is a single manufacturing inspection, which we’re working with the agency on in our facility in Italy. We’ve provided extensive documentation and currently work with the agency to try to maintain the action date of December 2020.”

Inclisiran is a subcutaneously administered siRNA that prevents the production of PCSK9 and is being developed as a potential treatment for hypercholesterolemia. Novartis added the product to its pipeline through the $9.7 billion acquisition of the Medicines Company in January this year.

The Medicines Company, which licensed inclisiran from Alnylam, did not have a manufacturing network of its own but worked with contract manufacturing organizations (CMO). According to its 2018 annual report, Alnylam provided finished inclisiran product for early-phase trials but the firm has inked contracts with Agilent Technologies and Nitto Denko Avecia for bulk drug substance. Contracts have also been forged with Alcami Corporation and Corden Pharma for bulk drug product production.

Agilent and Corden have facilities in Italy, though neither were cited by Novartis as the plant awaiting FDA inspection.