WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--
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 worldwide.
MSD is taking these steps based on the current understanding of the
preliminary data from the HPS2-THRIVE (eart rotection tudy
2-reatment of DL to educe the ncidence
of ascular vents) 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
Agencys Pharmacovigilance Risk Assessment Committee (PRAC) based on the
trials results.
In countries where the medicine is currently available, MSD has begun
informing regulatory agencies of the companys 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.
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.
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.
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.
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 [1]
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 MSDs 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; MSDs ability to accurately
predict future market conditions; manufacturing difficulties or delays;
financial instability of international economies and sovereign risk;
dependence on the effectiveness of MSDs 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 MSDs/Mercks 2011 Annual Report on Form 10-K and the companys
other filings with the Securities and Exchange Commission (SEC)
available at the SECs Internet site (www.sec.gov [2]).
Media:Pamela Eisele, 908-423-5042orSkip
Irvine, 267-305-5397orInvestors:Carol Ferguson,
908-423-4465
Source: MSD
