MSD Provides Update on Next Steps for TREDAPTIVE™ (nicotinic
WHITEHOUSE STATION, N.J. -- January 11, 2013
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^™ (nicotinic acid/laropiprant, MSD) modified-release tablets
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
“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
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/
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.
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.
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.
MSD undertakes no obligation to publicly update any forward-looking statement,
whether as a result of new information, future events or otherwise. Additional
factors that could cause results to differ materially from those described in
the forward-looking statements can be found in MSD’s/Merck’s 2011 Annual
Report on Form 10-K and the company’s other filings with the Securities and
Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Pamela Eisele, 908-423-5042
Skip Irvine, 267-305-5397
Carol Ferguson, 908-423-4465
Press spacebar to pause and continue. Press esc to stop.