Justify dose and rationality: CDSCO Panel Tells Alkem Laboratories on FDC Sacubitril plus Valsartan

Written By : Dr. Divya Colin |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2023-12-24T17:30:23+05:30 | Updated On 22 March 2024 10:53 PM IST

New Delhi: In response to the proposal for bioequivalence (BE) study and Phase III clinical trial (CT) waiver for Sacubitril 12mg plus Valsartan 13mg film-coated tablets presented by the drug major Alkem Laboratories, the Subject Expert Committee ( SEC) functional under the Central Drug Standard Control Organisation (CDSCO) has recommended the firm to submit more justification on the proposed dose and rationality of the fixed-dose combination of Sacubitril plus valsartan.

This came after Alkem Laboratories presented their proposal along with justification for the BE waiver and Phase III CT waiver before the committee.

Sacubitril is a neprilysin inhibitor used in combination with valsartan as an adjunct to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

Sacubitril's active metabolite, LBQ657 inhibits neprilysin, a neutral endopeptidase that would typically cleave natriuretic peptides, which includes: atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and c-type natriuretic peptide (CNP). ANP and BNP are released under atrial and ventricle stress, which activate downstream receptors leading to vasodilation, natriuresis, and diuresis. Under normal conditions, neprilysin breaks down other vasodilating peptides and vasoconstrictors such as angiotensin I and II, endothelin-1, and peptide amyloid beta-protein. Therefore, the inhibition of neprilysin leads to reduced breakdown and increased concentration of endogenous natriuretic peptides in addition to increased levels of vasoconstricting hormones such as angiotensin II.

Valsartan is an angiotensin-receptor blocker used to manage hypertension alone or in combination with other antihypertensive agents and to manage heart failure in patients who are intolerant to ACE inhibitors.

Valsartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which selectively bind to angiotensin receptor 1 (AT1) and prevent angiotensin II from binding and exerting its hypertensive effects.

At the recent SEC meeting for cardiovascular and renal held on 6th and 7th December 2023, the expert panel reviewed the proposal along with justification for BE waiver and Phase III CT waiver of the FDC Sacubitril plus Valartan presented by Alkem Laboratories.

After detailed deliberation, the committee opined, "More justification on the proposed dose and its rationality should be submitted for further review by the committee."

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Dr. Divya Colin

Doctor of Pharmacy

Dr. Divya Colin, a Doctor of Pharmacy Graduate with extensive experience in clinical and hospital settings and confidently equipped with diagnostic and therapeutic skills. She also has spread out exposure to Oncology Departments in Mysore Medical College and Research Institute as Oncology Pharmacist. Currently she is building a career in clinical research and clinical data management. She has been a part of Medical Dialogue since January 2022.

Dr. Kamal Kant Kohli

Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751