Submit in vitro data and comparative data: CDSCO Tells Dr Reddy's on Icosapent Ethyl Capsule
New Delhi: Noting that the effect of Icosapentether on the risk of pancreatitis in patients with severe hypertriglyceridemia has yet to be determined, the Subject Expert Committee (SEC) of the Central Drug Standard Control Organization (CDSCO) has advised drug major Dr. Reddy's Laboratories to submit in vitro and comparative data submitted during the product's approval in the United States for further review by the committee.
This was in line with the proposal presented by the drug major Dr. Reddy's Laboratories for the manufacture and marketing of Icosapent Ethyl Capsule 1 g for the following indications, along with bioequivalence (BE) and clinical trial (CT) waiver justification before the committee.
Icosapent ethyl is an ethyl ester of eicosapentaenoic acid (EPA) that reduces synthesis and enhances clearance of triglycerides and is used to treat patients with severe hypertriglyceridemia.
Icosapent ethyl or ethyl eicosapentaenoic acid, is a synthetic derivative of the omega-3 fatty acid eicosapentaenoic acid (EPA). It is used as an adjunct therapy for severe hypertriglyceridemia (TG levels > 500 mg/dL) and to reduce the risk of cardiovascular events in certain patients with elevated triglycerides.
Studies suggest that EPA reduces hepatic very low-density lipoprotein triglyceride (VLDL-TG) synthesis and/or secretion and enhances TG clearance from circulating VLDL particles. Potential mechanisms of action include increased β-oxidation; inhibition of acyl-CoA:1,2-diacylglycerol acyltransferase (DGAT); decreased lipogenesis in the liver; and increased plasma lipoprotein lipase activity.
The committee noted that the Icosapent Ethyl Capsule is an adjunct to maximally tolerated statin therapy to reduce the risk of myocardial infarction, stroke, coronary revascularization, and unstable angina requiring hospitalization in adult patients with elevated triglyceride (TG)levels (150 mg/dl) and established cardiovascular disease or diabetes mellitus and or more additional risk factors for cardiovascular disease as an adjunct to diet to reduce TG levels in adult patients with severe 500 mg/dl) hypertriglyceridemia.
Regarding the limitations of use, the expert panel observed that the effect of Icosapentethyl on the risk of pancreatitis in patients with severe hypertriglyceridemia has not been determined.
Furthermore, it was noted that, in accordance with the data available on the CDSCO website, Icosapent Ethyl Capsules, 1 g, are not approved by the Office of the Drug Controller General of India (DCGI); however, in a fixed-dose combination, they are approved as follows:
(1) Eicosapentaenoic acid + Docosahexaenoic acid capsules (Each capsule contains; Eicosapentaenoic acid- 180mg, Docosahexaenoic acid-120mg) 1989.
In addition to the above, and in line with the regulatory approval status in other countries, the expert panel noticed that Icosapent Ethyl Capsules 1g, under the trade name of (Vascepa), were approved for the treatment of expanded cardiovascular disease (CVD) risk reduction indications in the USA (approved on 13.12.2019), Canada (approved on30.12.2019) and Europe (approved on 20.04.2021).
At the recent SEC meeting for Cardiovascular and Renal held on December 8, 2022, the expert panel extensively reviewed the proposal presented by the firm to manufacture and market the anti-lipemic drug Icosapent Ethyl Capsule along with the BE and CT waiver justification.
After detailed deliberation, the committee recommended,
"A clinical trial waiver be considered, however, the firm should submit in-vitro data/ comparative data submitted during the approval of their product in the USA, for further review by the committee."
