FDA rebuffs Novartis' cholesterol drug inclisiran in an 'inspection-related' approval delay

The FDA sent Novartis a complete response letter for its inclisiran application as COVID-19 made it difficult to conduct an on-site manufacturing inspection. (Novartis)

Manufacturing inspection-related woes have derailed another FDA approval this year, this time for a drug at the center of a $9.7 billion acquisition.

Novartis’ cholesterol drug inclisiran was turned back by the FDA due to “unresolved facility inspection-related conditions,” which will be detailed to the inclisiran manufacturing site within 10 business days, the Swiss pharma said Friday.

It’s a setback for Novartis on its path toward blockbuster sales of the PCSK9 drug, featured in the buyout of The Medicines Company. But at least the holdup looks to be only temporary.

The FDA didn’t raise any concerns about inclisiran’s efficacy or safety, Novartis said. The no-go is “essentially due to COVID-19 travel restrictions (FDA couldn't inspect a third-party facility),” RBC Capital Markets analyst Luca Issi said in a Sunday note.

Novartis CEO Vas Narasimhan said in late October that the company had been working with the FDA on the inspection of a facility in Italy as the one last remaining item to cross off on inclisiran’s review list.

But as of Friday, “[n]o onsite inspection was conducted of the single third-party facility in question,” Novartis said. “If a facility inspection is needed, FDA will define an approach once safe travel may resume based on public health need and other factors.”

RELATED: Novartis' $9.7B MedCo buyout bears first fruit as blockbuster-to-be inclisiran nabs EU nod

As of Monday morning, Italy has recorded nearly 2 million COVID-19 cases, with about 69,000 deaths, according to Johns Hopkins University’s count.

Noting that inclisiran’s own profile is not at question, Issi called the CRL “fairly benign” in a note about Alynlam. Inclisiran was designed using Alnylam’s RNA interference technology to target production of the PCSK9 protein in the liver. The Massachusetts biotech is on tap for milestone payments and royalties related to inclisiran.

Issi expects the approval may be delayed by about six months. Inclisiran won a green light in Europe under the brand Leqvio a few days ago.

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“Novartis is confident in the quality of the regulatory submission for inclisiran, which includes a robust body of evidence related to efficacy and safety,” Novartis Chief Medical Officer John Tsai, M.D., said in a statement. “We look forward to meeting with the FDA and our third-party manufacturing partner to discuss the feedback received and next steps.”

COVID-19 has prevented FDA staffers from conducting preapproval manufacturing inspections for other drugs before inclisiran. A decision for Bristol Myers Squibb’s CAR-T therapy liso-cel, for instance, was pushed back after the FDA missed its November deadline without a site inspection, endangering the $9-apiece contingent value rights that will only be paid out if the drug secures the approval by year-end.