Drugs Xagena
Merck, known as MSD outside the United States and Canada, issued the following statement after the conclusion of a meeting of the Endocrinologic and Metabolic Drugs Advisory Committee of the U.S. Food and Drug Administration ( FDA ) to discuss the results of IMPROVE-IT, an investigational study comparing treatment with Vytorin ( Ezetimibe and Simvastatin ) to treatment with Simvastatin alone in more than 18,000 patients presenting with acute coronary syndromes.
FDA Advisory Committee rejected Merck’s request that labelling for cholesterol-lowering drug Vytorin should include a claim of reducing myocardial infarctions and strokes.
The Panel members reviewed data from IMPROVE-IT trial but were not swayed by the data and voted 10 to 5 to reject the proposed label change.
Merck believes that IMPROVE-IT showed that Ezetimibe in combination with a statin offers a significant benefit to high-risk patients with coronary heart disease and is committed to continuing to work with the FDA so that they can complete the review of the request for new indications for Vytorin and Zetia ( Ezetimibe ).
Merck believes that the results of the IMPROVE-IT trial address an important medical need in patients on statin therapy who are high-risk for cardiovascular events.
Vytorin and Zetia are currently indicated for use along with a healthy diet to reduce elevated LDL cholesterol in patients with hyperlipidemia. The current U.S. Prescribing Information for both products states that the effect of Ezetimibe on cardiovascular morbidity and mortality, alone or incremental to statin therapy, has not been determined.
Merck has submitted the data from the IMPROVE-IT study to the FDA to support a new indication for reduction of cardiovascular events for Zetia and Vytorin.
IMPROVE-IT Trial
IMPROVE-IT ( IMProved Reduction of Outcomes: Vytorin Efficacy International Trial ) was led by the Thrombolysis In Myocardial Infarction ( TIMI ) Study Group of Brigham and Women’s Hospital and the Duke Clinical Research Institute ( DCRI ), and was sponsored by Merck.
IMPROVE-IT was an international, multi-center, randomized, double-blind active comparator trial of 18,144 patients presenting with high-risk acute coronary syndromes ( ACS ), including unstable angina ( UA ), non-ST-segment elevation acute myocardial infarction ( NSTEMI ), and ST-segment elevation acute myocardial infarction ( STEMI ).
The study assessed the incidence of major cardiovascular events, as measured by a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, re-hospitalization for unstable angina, or coronary revascularization ( occurring 30 days or more after the initial event ), in patients treated with Ezetimibe and Simvastatin compared with patients treated with Simvastatin alone.
All patients in the trial were started at doses of Ezetimibe and Simvastatin 10/40 mg or Simvastatin 40 mg alone. Prior to a 2011 protocol amendment, the dose could be titrated to Ezetimibe / Simvastatin 10/80 mg or Simvastatin 80 mg if successive LDL-C values exceeded 79 mg/dL.
The study enrolled patients within 10 days of ACS hospitalization who had sufficient risk as defined in the protocol and who had an initial LDL-C of less than or equal to 125 mg/dL if lipid-lowering drug naïve or less than 100 mg/dL if on a prior prescription lipid-lowering therapy identified as no more potent than Simvastatin 40 mg/day.
The LDL-C entry limitations were designed to enroll patients who were reasonably anticipated to achieve LDL-C levels of 70 mg/dL or less in the Simvastatin only cohort, which was the optional recommended target set in the 2004 update to the Adult Treatment Panel (ATP) III guidelines. ( Xagena )
Source: Merck, 2015
XagenaMedicine_2015
