Renewed Hope for Inclisiran as Novartis Announces Complete Response Resubmission to US FDA

Less than 7 months after receiving a complete response letter for their New Drug Application (NDA) for inclisiran in December, Novartis has announced the Complete Response resubmission to the US Food and Drug Administration (FDA) for the inclisiran NDA.

With the FDA’s December 2020 CRL citing unresolved facility inspections issues, Novartis announced it will now be using a Novartis-owned facility based in Austria for the manufacturing of inclisiran, according to a statement from Novartis.

“Novartis is confident in the quality of the regulatory submission for inclisiran, which includes a robust body of evidence related to efficacy and safety. We look forward to meeting with the FDA and our third-party manufacturing partner to discuss the feedback received and next steps,” said John Tsai, Head Global Drug Development and Chief Medical Officer at Novartis, in a statement from Novartis at the time the FDA issued the original CRL. “We are committed to bringing this potential first-in-class small interfering RNA cholesterol-lowering treatment to patients as soon as possible.”

An injectable small interfering RNA, the novel, first-in-class drug with the potential for twice-yearly dosing has been in the spotlight among lipidologists since the first results of the ORION program were published. Following a splash at AHA 2019, Novartis acquired inclisiran and The Medicine Company for $9.7 billion.

Prior to being acquired by Novartis, The Medicines Company had filed an NDA for inclisiran with the FDA in December 2019. The FDA issued a CRL on December 18, 2020, which was 5 days prior to the December 23 PDUFA date, detailing issues with inspection-related conditions at a third-party manufacturing facility in Europe.

In its latest statement, Novartis pointed out the choice to transfer the manufacturing of inclisiran to Austria-based, Novartis-owned facility was planned and initiated prior to the receipt of the FDA’s CRL. Additionally, Novartis also noted an update on the status of the Complete Response resubmission would be provided after the FDA has determined the response resubmission is complete.

To learn more about inclisiran, check out our interview with Kausik Ray, MD, PhD, on the ORION program from last year’s European Society of Cardiology Congress (ESC 2020).