Explain the Dosage and Reasoning: CDSCO Panel Notifies Lupin on FDC Sacubitril with Valsartan

The Subject Expert Committee (SEC) operating under the Central Drug Standard Control Organization (CDSCO) has recommended that the company submit additional justification regarding the suggested dose and its rationality for more evaluation. This is in response to the justification provided by the drug major Lupin regarding the rationality of the fixed-dose combination (FDC) cardiovascular drug Sacubitril plus Valsartan tablet 25 mg.

This occurred following Lupin, the drug company, presented the committee with the Phase III clinical trial protocol and reason for the suggested dose.

A neprilysin inhibitor called sacubitril is used as an adjuvant with valsartan to lower the risk of cardiovascular death and heart failure hospitalization in patients with diminished ejection fraction and chronic heart failure (NYHA Class II–IV).

Sacubitril is a prodrug that esterases de-ethylate to produce sacubitrilat. Sacubitrilat inhibits neprilysin, an enzyme that breaks down brain and atrial natriuretic peptides, two peptides that reduce blood pressure mostly via decreasing blood volume.

ARBs, or angiotensin II receptor blockers, include valsartan. It functions by obstructing an internal substance that causes the body's blood arteries to constrict. By relaxing blood arteries, valsartan reduces blood pressure. Blood and oxygen flow to the heart will both rise with a drop in blood pressure.

Adults with chronic heart failure can benefit from the FDC of sacubitril and valsartan, which lowers their risk of death and hospitalization. Additionally, children with symptomatic heart failure are treated with this medication. ARBs, or angiotensin II receptor blockers, include valsartan.

The expert panel examined the Phase III clinical study protocol provided by drug maker Lupin, as well as the rationale and explanation for the suggested dose, during the most recent SEC conference for cardiovascular, which took place on July 18, 2024.

Following a thorough investigation, the committee restated its prior advice to provide CDSCO with further evidence supporting the suggested dosage and its rationale so that the committee may evaluate it in more detail.

(Input from various sources)

(Rehash/Priyanka Pandey/MSM)