- The Food and Drug Administration last week informed Novartis that it would not be able to complete its review as scheduled of the Swiss drugmaker's closely watched cholesterol drug inclisiran, issuing a complete response letter that could delay a decision on approval for months.
- At issue are "unresolved" conditions related to an as-yet unscheduled inspection of a facility in Italy where Novartis manufactures inclisiran. Due to the coronavirus pandemic, FDA inspectors haven't been able to visit and inspect the site.
- Novartis emphasized the FDA's letter did not raise any issues with either the safety or efficacy of inclisiran, which was shown in clinical testing to significantly reduce cholesterol levels in people already taking statins. The pharma hopes to quickly resolve the remaining conditions but, should an inspection be required, completion of inclisiran's review would be delayed until the FDA restarts foreign country inspections.
Inclisiran is an important drug for Novartis, obtained via the company's nearly $10 billion buyout of The Medicines Company a little over a year ago.
The powerful cholesterol-lowering therapy shares the same target as approved medicines from Amgen and Regeneron, but works differently, relying on Nobel Prize-winning science that's given drugmakers a new tool to "silence" production of disease-causing proteins.
While the Amgen and Regeneron drugs have struggled to live up to lofty sales forecasts, Novartis executives have set high expectations for inclisiran, which they argue is more convenient and delivers sustained benefit over time.
Approval was expected by the December decision date the FDA set for Novartis' application but, with foreign travel restricted, agency inspectors weren't able to check the last box in the drug's review.
Victor Bulto, Novartis' head of U.S. pharmaceuticals, previously told BioPharma Dive the company had tried to resolve those conditions of the review without an inspection, describing the issue as mostly a matter of "paperwork."
"In a normal, non-COVID world, it would be a simple inspection," Bulto said in a Dec. 16 interview. The European Commission this month authorized inclisiran under the brand name Leqvio.
Other drugs have faced similar holdups. Most notably, in November, the FDA delayed a decision on a Bristol Myers Squibb cell therapy after COVID-19 travel restrictions derailed an inspection of a Texas plant involved in manufacturing. Other medicines from Revance Therapeutics and South Korea's Hanmi Pharmaceuticals have also been affected.
"Since the CRL is not related to safety or efficacy concerns, we are hopeful that the third-party facility inspection-related conditions can be resolved as quickly as possible," a Novartis spokesperson wrote in an email to BioPharma Dive. "However, if FDA decides an inspection is required the timing will be dependent on FDA’s ability to restart foreign inspections."
Should Novartis win an approval of inclisiran as anticipated, the company will have work to do launching a new therapy into a competitive drug class.
Amgen and Regeneron have several years' head start in selling, respectively, Repatha and Praluent, which are both aimed at the PCSK9 protein that inclisiran targets. Importantly, both drugs are each backed by data from large cardiovascular outcomes studies that proved a heart benefit, albeit more modest than some had hoped.
The two drugmakers were forced to significantly cut their prices after many insurers blocked coverage of the drugs, further muddying the market Novartis hopes to enter.
"We will price at a level that will allow us to have a broader impact on society and allows us to minimize non-clinical barriers," said Novartis' Bulto.
The Swiss pharma plans to use the salesforce it's built behind its heart failure drug Entresto to market inclisiran, if the FDA ultimately grants an approval.