MSD, known as Merck (NYSE: MRK) in the United States and Canada, today announced the company is taking steps to suspend the availability of TREDAPTIVE TM (nicotinic acid/laropiprant, MSD) modified-release tablets worldwide.
MSD is taking these steps based on the current understanding of the preliminary data from the HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) study, and in consultation with regulatory authorities. As previously reported by MSD (Dec. 20, 2012 news release), HPS2-THRIVE did not achieve its primary endpoint of reduction of major vascular events, and there was a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received TREDAPTIVE compared to statin therapy. The decision to suspend availability of the medicine is aligned with the recommendation of the European Medicine Agency´s Pharmacovigilance Risk Assessment Committee (PRAC) based on the trial´s results.
In countries where the medicine is currently available, MSD has begun informing regulatory agencies of the company´s decision. MSD is working with these agencies to develop communications for health care providers and to suspend the availability of TREDAPTIVE, with the timing to be based on individual country regulations and processes.
MSD is recommending that physicians stop prescribing TREDAPTIVE. MSD is also recommending that physicians review treatment plans for patients taking TREDAPTIVE in a timely manner to discontinue TREDAPTIVE and consider other changes in therapy to achieve their dyslipidemia management goals. In the meantime, MSD encourages patients with questions to speak with their health care provider, and to not discontinue therapy without first speaking with their physician.
"Patients currently taking TREDAPTIVE are our priority, and we are committed to continue to work with regulatory agencies around the world to ensure that physicians have appropriate information as we take steps to suspend the availability of TREDAPTIVE," said Michael Rosenblatt, M.D., Chief Medical Officer, MSD.
About the HPS 2-THRIVE Study
HPS2-THRIVE was independently conducted by the Clinical Trial Service Unit at Oxford University and funded by MSD. With the agreement of the independent research team at Oxford University, Merck is sharing results from the study with regulatory agencies. The investigators are conducting additional analyses to further understand the results. They anticipate reporting the detailed study results in the first quarter of 2013.
The study enrolled 25,673 patients considered to be at high risk for cardiovascular events. Of those enrolled, 14,741 were from Europe (the United Kingdom and Scandinavia) and 10,932 were from China. Patients in the study were followed for a median of 3.9 years. HPS2-THRIVE compared modified release nicotinic acid and laropiprant plus statin therapy versus statin therapy. It was not designed to assess directly the separate effects of either modified-release nicotinic acid or laropiprant.
In the study, adding the combination of modified release nicotinic acid and laropiprant to statin therapy did not significantly further reduce the risk of the combination of coronary deaths, nonfatal heart attacks, strokes or revascularizations compared to statin therapy. In addition, there was a statistically significant increase in the incidence of some types of non-fatal serious adverse events in the group that received modified release nicotinic acid and laropiprant.
Preliminary analyses suggest that the adverse events fall within the following broad categories: blood and lymphatic, gastrointestinal, infections, metabolism, musculoskeletal, respiratory and skin. Additional analyses are ongoing to understand the adverse events within these categories.
TREDAPTIVE has been approved in approximately 70 countries, including in Europe, and is sold in approximately 40 countries. TREDAPTIVE is also sold under the brand names PELZONT in Italy and TREVACLYN in Italy and Portugal and CORDAPTIVE in other markets around the world.
Selected Product Information About TREDAPTIVE
Current Therapeutic Indications
TREDAPTIVE is indicated for the treatment of dyslipidemia, particularly in patients with combined mixed dyslipidemia (characterized by elevated levels of LDL-C and TG and low HDL-C) and in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial).
TREDAPTIVE should be used in patients in combination with HMG-CoA reductase inhibitors (statins), when the cholesterol-lowering effect of statin monotherapy is inadequate. It can be used as monotherapy only in patients in whom statins are considered inappropriate or not tolerated. Diet and other nonpharmacological treatments (e.g., exercise, weight reduction) should be continued during therapy with TREDAPTIVE.
Selected Safety Information About TREDAPTIVE
TREDAPTIVE is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients, significant or unexplained hepatic dysfunction, active peptic ulcer disease, or arterial bleeding.
The most common side effect of TREDAPTIVE is flushing (skin redness, warmth, and itching). Other common side effects include dizziness, headache, paresthesia, diarrhea, dyspepsia, nausea, vomiting, erythema, pruritus, rash, urticaria, feeling hot, and elevations in ALT or AST (consecutive, ? 3X ULN), fasting glucose, and uric acid.
Liver function tests are recommended before initiation, every 6 to 12 weeks for the first year, and periodically (e.g., semiannually) thereafter. Should an increase in ALT or AST of ?3X ULN persist, reduction of dose or withdrawal of TREDAPTIVE is recommended
Physicians contemplating combined therapy with statins and TREDAPTIVE should carefully weigh the potential benefits and risks and should carefully monitor patients for myopathy (muscle pain, tenderness, or weakness), particularly during the initial months of therapy and when the dose of either drug is increased (periodic serum CK should be considered in such situations).
If muscle pain, weakness, or cramps occur while a patient is receiving TREDAPTIVE with a statin, their CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (> 5X ULN), treatment should be stopped.
Caution should be used when treating Chinese patients with TREDAPTIVE coadministered with simvastatin or ezetimibe/simvastatin (particularly simvastatin doses of 40mg or higher) because of a higher than expected incidence of myopathy in those patients. Because the risk of myopathy with statins is dose-related, the use of TREDAPTIVE with simvastatin 80 mg or ezetimibe/simvastatin 10/80 mg is not recommended in Chinese patients. It is unknown whether there is an increased risk of myopathy in other Asian patients treated with TREDAPTIVE coadministered with simvastatin or ezetimibe/ simvastatin.
Diabetic or potentially diabetic patients should be observed closely. Adjustment of diet and/or hypoglycemic therapy may be necessary. TREDAPTIVE should be used with caution in patients with renal dysfunction, acute coronary syndrome, risk for hypophosphatemia, or gout (or predisposed to gout). As with other nicotinic acid products, TREDAPTIVE was associated with a small reduction in platelet count. Therefore, patients undergoing surgery should be carefully evaluated. Patients with a history of jaundice, hepatobiliary disorder, or peptic ulcer should be observed closely.
A clinical study to evaluate the effect of laropiprant on platelet function in patients concomitantly receiving both acetylsalicylic acid and clopidogrel was inconclusive. Because this study did not rule out the potential for prolongation of bleeding time, patients receiving TREDAPTIVE concomitantly with acetylsalicylic acid and clopidogrel should be closely monitored.
About MSD
Today´s MSD is a global healthcare leader working to help the world be well. MSD is known as Merck inside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.msd.com and connect with us on Twitter, Facebook and YouTube.
Forward-Looking Statement
This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of MSD´s management and are subject to significant risks and uncertainties. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; MSD´s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of MSD´s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
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