Novartis proposal to market Inclisiran with clinical trial waiver rejected by CDSCO panel

This came in the wake of the proposal presented by the firm to import and market Inclisiran Solution for Injection in pre-filled syringes of 284 mg/1.5 mL with a local clinical trial waiver before the committee.

Inclisiran is the first and only small interfering RNA (siRNA) therapy to reduce low-density lipoprotein cholesterol (LDL-C) levels via an RNA interference (RNAi) mechanism of action and could help improve outcomes for patients with atherosclerotic cardiovascular disease (ASCVD), a deadly form of cardiovascular disease.

Inclisiran is a long-acting, synthetic small interfering RNA (siRNA) directed against proprotein convertase subtilisin-kexin type 9 (PCSK9), which is a serine protease that regulates plasma low-density lipoprotein cholesterol (LDL-C) levels.

Inclisiran prevents protein translation of PCSK9 by binding to PCSK9 messenger RNA, leading to decreased concentrations of PCSK9 and plasma concentrations of LDL cholesterol. Lowering circulating plasma LDL-C levels offers an additional benefit of reducing the risk of cardiovascular disease (CVD) and improving cardiovascular outcomes.

Last year, in December, Novartis received EU approval for Leqvio (inclisiran), a first-in-class siRNA to lower cholesterol with two doses a year. This approval was based on the results of the robust ORION clinical development program, where Leqvio provided an effective and sustained low-density lipoprotein cholesterol (LDL-C) reduction of up to 52% in patients with elevated LDL-C, despite maximally tolerated statin therapy.

With two doses a year, after an initial dose and one at 3 months, Leqvio is expected to support long-term adherence.

Earlier, the Medical Dialogues Team had reported that Novartis had announced that the U.S. Food and Drug Administration (USFDA) issued a complete response letter (CRL) regarding the new drug application (NDA) for inclisiran. The FDA stated that the agency could not approve the NDA by the Prescription Drug User Fee Act (PDUFA) action date of December 23, 2020, due to unresolved facility inspection-related conditions.

Moving further, at a recent SEC meeting held on 08.10.2021 and 11.10.2021at CDSCO for Cardiovascular & Renal, the committee thoroughly examined the drug-maker Novartis Healthcare's proposal for the import and marketing of the Inclisiran Solution for Injection in pre-filled syringes of 284 mg/1.5 mL with a local clinical trial waiver.

After extensive evaluation, the committee observed that the justification for the local clinical trial waiver was not adequate as per the rules, and there is no unmet medical need for the proposed indication in the country.

After detailed deliberation, the committee did not recommend a local clinical trial waiver and opined that the firm should conduct a Phase III clinical trial in the country.

Accordingly, the committee directed the firm to submit the Phase III clinical trial protocol to CDSCO for further review by the committee.