merck & co. inc. (MRK) Key Developments
Merck & Co. Inc. Announces Results from New Analyses of IMPROVE-IT Study
Sep 1 15
Merck & Co. Inc. announced results from new analyses from the IMPROVE-IT study. VYTORIN (ezetimibe and simvastatin) and ZETIA (ezetimibe) 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 U.S. Food and Drug Administration to support a new indication for reduction of cardiovascular events for ZETIA and VYTORIN. The results of one of the analyses presented at ESC showed that patients treated with VYTORIN® – which combines simvastatin with the non-statin ZETIA® - showed a similar risk of new onset diabetes mellitus (DM) compared to simvastatin alone over a period of >5.5 years median follow-up. During the trial, 1,414 patients (13.3% of those without diabetes at enrollment) developed new onset DM defined as initiation of a diabetes medication or two consecutive fasting glucose levels =7 mmol/L (126 mg/dL). Of the new onset DM cases, 50.9% occurred in the VYTORIN (ezetimibe and simvastatin) arm and 49.1% in the simvastatin arm (hazard ratio 1.04; 95% CI 0.94-1.15). This post-hoc analysis compared safety and efficacy data during the median six years follow-up in patients stratified by achieved LDL-C at month one of the trial. This analysis assessed patients achieving LDL-C levels <30 mg/dL, 30 - <50 mg/dL, 50 - <70 mg/dL and =70 mg/dL at month one of the trial. The nine selected safety events of special interest, which included hemorrhagic stroke and adverse events leading to treatment discontinuation, showed similar rates in patients with LDL-C <30 mg/dL at month one (achieved by 6% of patients) compared with patients with higher achieved LDL-C levels. In addition, this analysis concluded that cardiovascular events occurred less frequently in patients who achieved an LDL-C level <70 mg/dL at month 1 of the trial compared with LDL-C levels =70 mg/dL. Additional evidence relating to the efficacy of VYTORIN comes from another IMPROVE-IT analysis, which assessed outcomes in subjects achieving specific levels of LDL-C and high sensitivity C-reactive protein (hs-CRP). CRP levels, a marker of inflammation, are associated with a higher cardiovascular risk in some settings. This analysis showed that patients achieving both LDL-C <70 mg/dL and hs-CRP <2 mg/L at one month had a lower rate of the primary composite endpoint of major CV events over the course of the trial compared with patients not achieving either level. Significantly more patients treated with VYTORIN met these specified dual levels at month one compared to patients treated with simvastatin alone (50% vs 29%, p<0.001). 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 high-risk patients presenting with 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 CV events, as measured by a composite of CV death, non-fatal MI, non-fatal stroke, re-hospitalization for ACS or coronary revascularization (occurring 30 days or more after the initial event), in patients treated with ezetimibe/simvastatin (VYTORIN) 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. 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 =125 mg/dL if lipid-lowering drug naïve or <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 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.
Merck Announces New Analyses from the Investigational IMPROVE-IT Study of VYTORIN, the TECOS and Real-World Data from the Dyslipidemia International Study
Aug 20 15
Merck announced that new analyses from the investigational IMPROVE-IT (IMProved Reduction of Outcomes: VYTORIN Efficacy International Trial) study of VYTORIN (ezetimibe and simvastatin), the TECOS (Trial Evaluating Cardiovascular Outcomes with Sitagliptin) cardiovascular safety trial of JANUVIA (sitagliptin), and real-world data from the Dyslipidemia International Study (DYSIS I and DYSIS II) will be presented at the upcoming European Society of Cardiology (ESC) Congress 2015, held August 29 to September 2, 2015. IMPROVE-IT was designed to evaluate the cardiovascular benefit of the combination of ezetimibe and simvastatin compared to simvastatin alone. The TECOS cardiovascular safety trial was designed to assess the cardiovascular safety of Merck’s DPP-4 inhibitor, JANUVIA. In all, Merck has 13 data presentations at this year’s ESC. The primary results from IMPROVE-IT, which enrolled 18,144 high-risk patients presenting with acute coronary syndromes (ACS), were presented in November 2014 at the American Heart Association Scientific Sessions and published in The New England Journal of Medicinein June 2015. VYTORIN and ZETIA (ezetimibe)are indicated for use along with a healthy diet to reduce elevated LDL cholesterol in patients with hyperlipidemia. The current U.S. Prescribing Information for VYTORINand ZETIA 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 IMPROVE-IT to regulatory authorities in the U.S. and European Union to support a new indication for reduction of major cardiovascular events for VYTORIN and ZETIA. TECOS was an event-driven study of more than 14,000 patients that evaluated the long-term cardiovascular safety of the addition of JANUVIA to usual care, compared to usual care without JANUVIA, in patients with type 2 diabetes and established cardiovascular disease. The primary results of the TECOS cardiovascular safety trial were presented at the 75th Scientific Sessions of the American Diabetes Association and published simultaneously in the New England Journal of Medicine in June 2015. Indications and Limitations of Use for JANUVIA (sitagliptin) 25 mg, 50 mg and 100 mg tablets: JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. JANUVIA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.
Merck Recalls TEMODAR and Temozolomide Bottles with Cracked Caps Due to Failure to Meet Child–Resistant Closure Requirement
Aug 18 15
Merck announced in conjunction with the U.S. Consumer Product Safety Commission asked that all customers, including patients, inspect all bottles of TEMODAR capsules and all bottles of Temozolomide capsules for potential cracks in the child-resistant bottle caps. The medicine is manufactured by Merck and distributed in the United States by Merck as TEMODAR. The Temozolomide capsules are manufactured and packaged by Merck but sold and distributed by Sandoz, the authorized generic partner, under the Sandoz label. In addition to these supplies, Merck also provides TEMODAR in the United States in sachets; TEMODAR in sachets are not affected. Merck believes that approximately 1,100 bottles out of an estimated 276,000 distributed bottles of TEMODAR and Temozolomide capsules could potentially have cracked caps. Those bottles could be at wholesalers, pharmacies, healthcare providers or with patients.
FDA Accepts Supplemental Biologics License Application for KEYTRUDA® of Merck
Aug 18 15
Merck announced that the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental Biologics License Application for KEYTRUDA®, Merck's anti-PD-1 therapy. Merck is seeking approval for KEYTRUDA, at the currently approved dose of 2 mg/kg every three weeks, for the first-line treatment of unresectable or metastatic melanoma patients. The FDA granted Priority Review with a PDUFA, or target action, date of December 19, 2015. Additionally, the FDA has extended the action date for a separate sBLA for KEYTRUDA for the treatment of patients with ipilimumab-refractory advanced melanoma. The new action date is now December 24, 2015. Through the clinical program for KEYTRUDA it has accumulated substantial data on the role of anti-PD-1 therapy in advanced melanoma. The company looks forward to the FDA's review of each of these applications, and to delivering on the goal of helping patients with advanced melanoma to achieve long-term disease control and survival. KEYTRUDA is currently indicated in the United States at a dose of 2 mg/kg administered as an intravenous infusion over 30 minutes every three weeks for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
Merck and MD Anderson Cancer Center Announce Strategic Immuno-Oncology Research Collaboration in Solid Tumors
Aug 13 15
Merck and The University of Texas MD Anderson Cancer Center announced that they have entered into a strategic clinical research collaboration to evaluate Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab), in combination with other treatments, such as chemotherapy, radiation therapy and/or novel antitumor medicines. Under the terms of the agreement, collaborative studies will be conducted in the following tumor types: gastroesophageal adenocarcinoma, pancreatic adenocarcinoma, and hepatocellular carcinoma -- over the three year period of the collaboration. The first studies are scheduled to start enrolling later 2015. The agreement aims to define what combination modalities will work best with KEYTRUDA in these types of tumors by exploring promising new alternatives. The studies will be conducted in parallel, in order to determine optimal regimens in the most efficient manner possible.