FDA Issues CRL for Inclisiran

The US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) for inclisiran (KJX839), a potential treatment for hyperlipidemia in adults with elevated low-density lipoprotein cholesterol (LDL-C) on a maximum tolerated dose of a statin therapy.

The agency was unable to approve the New Drug Application (NDA) submitted by Novartis because of unresolved facility inspection-related conditions.

Ultimately the company believes the issues regarding the manufacturing facilities will be sufficiently addressed in the future.

“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,” John Tsai, Head Global Drug Development and Chief Medical Officer, Novartis, said in a statement. “We are committed to bringing this potential first-in-class small interfering RNA cholesterol-lowering treatment to patients as soon as possible.”

The treatment potentially represents the first and only small interfering RNA (siRNA) therapy to reduce LDL-C levels through an RNA interference (RNAi) mechanism of action. This could improve outcomes for patients with atherosclerotic cardiovascular disease (ASCVD).

The treatment would be taken twice a year as a complement to statins, preventing the production of the target protein in the liver, increasing hepatic uptake of LDL-C, and clearing it from the bloodstream.

The NDA was based on data from 3 clinical trials showing inclisiran maintained LDL-C reduction throughout each six-month dosing interval. The drug was also well-tolerated, with the most common adverse events being injection site reaction, arthralgia, urinary tract infection, diarrhea, bronchitis, pain in extremity, and dyspnea.