Merck Receives CHMP Positive Opinion Recommending Approval of ISENTRESS® (raltegravir) 600 mg in the European Union


May 19, 2017 7:00 am ET

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the Committee for Medicinal Products for Human
Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive
opinion recommending approval of ISENTRESS® (raltegravir) 600
mg film-coated tablets, in combination with other anti-retroviral
medicinal products, for the treatment of HIV-1 infection in adults and
pediatric patients weighing at least 40 kg. In adults and pediatric
patients (weighing at least 40 kg), the recommended dosage is 1,200 mg
(two 600 mg tablets) once daily for treatment-naïve patients or patients
who are virologically suppressed on an initial regimen of ISENTRESS 400
mg twice daily. The recommendation will now be reviewed by the European
Commission for marketing authorization in the European Union. A decision
on approval is expected in the second half of 2017.

The once daily formulation of ISENTRESS is currently under review in the
United States by the Food and Drug Administration.

“The CHMP’s positive opinion recommending the approval of ISENTRESS 600
mg film-coated tablets is an important step toward a new option for
people living with HIV who are looking for once-daily dosing, as part of
an HIV treatment regimen, with proven efficacy and safety,” said Dr.
Eliav Barr, senior vice president, global clinical development,
infectious diseases and vaccines, Merck Research Laboratories.

The CHMP positive opinion was based on findings from the ONCEMRK trial,
an ongoing Phase 3 multicenter, double-blind, randomized, active
comparator-controlled clinical trial designed to evaluate the efficacy
and safety of ISENTRESS 1200 mg, given as two 600 mg oral tablets once
daily, compared to ISENTRESS 400 mg twice daily, each in combination
with emtricitabine + tenofovir disoproxil fumarate in previously
untreated HIV-1 infected adults. Once-daily ISENTRESS 600 mg (1200 mg
total), when used as part of an HIV-1 treatment regimen, demonstrated
comparable efficacy and safety to ISENTRESS 400 mg twice a day after
48-weeks of treatment across a variety of patient populations.

About ISENTRESS (raltegravir)

ISENTRESS is Merck’s integrase inhibitor for the treatment of HIV-1
infection in adult and pediatric patients aged four weeks and older and
weighing at least 3 kg as part of combination HIV therapy. ISENTRESS
works by inhibiting the insertion of HIV-1 DNA into human DNA by the
integrase enzyme and has demonstrated rapid antiviral activity.
Inhibiting integrase from performing this essential function limits the
ability of the virus to replicate and infect new cells.

ISENTRESS is approved as part of combination therapy in 112 countries
for treatment of HIV-1 infection in adults. ISENTRESS chewable tablets,
in combination therapy, for use in children and adolescents with HIV-1
aged two years and older has also been approved for use in 69 countries,
and ISENTRESS granules for oral suspension for infants at least four
weeks of age is approved for use in 33 countries.

Selected Important Safety Information for ISENTRESS



Severe, potentially life-threatening and fatal skin reactions have been
reported. This includes cases of Stevens-Johnson syndrome,
hypersensitivity reaction and toxic epidermal necrolysis. Immediately
discontinue treatment with ISENTRESS and other suspect agents if severe
hypersensitivity, severe rash, or rash with systemic symptoms or liver
aminotransferase elevations develops and monitor clinical status,
including liver aminotransferases closely.

Immune reconstitution syndrome can occur, including the occurrence of
autoimmune disorders with variable time to onset, which may necessitate
further evaluation and treatment.

ISENTRESS chewable tablets contain phenylalanine, a component of
aspartame, which may be harmful to patients with phenylketonuria.

Co-administration of ISENTRESS with drugs that are strong inducers of
uridine diphosphate glucuronosyltransferase (UGT) 1A1 may result in
reduced plasma concentrations of raltegravir. Co-administration of
ISENTRESS with drugs that inhibit UGT1A1 may increase plasma levels of

Co-administration of ISENTRESS and other drugs may alter the plasma
concentration of raltegravir. The potential for drug-drug interactions
must be considered prior to and during therapy. Co-administration or
staggered administration of aluminum and/or magnesium
hydroxide-containing antacids and ISENTRESS is not recommended.

Rifampin, a strong inducer of UGT1A1, reduces plasma concentrations of
ISENTRESS. Therefore, the dose of ISENTRESS for adults should be
increased to 800 mg twice daily during co-administration with rifampin.
There are no data to guide co-administration of ISENTRESS with rifampin
in patients below 18 years of age.

The most commonly reported (≥2 percent) drug-related clinical adverse
reactions of moderate to severe intensity in treatment-naïve adult
patients receiving ISENTRESS compared with efavirenz were insomnia (4
percent vs. 4 percent), headache (4 percent vs. 5 percent), nausea (3
percent vs. 4 percent), fatigue (2 percent vs. 3 percent), and dizziness
(2 percent vs. 6 percent) respectively. Intensities were defined as
follows: Moderate (discomfort enough to cause interference with usual
activity); or Severe (incapacitating with inability to work or do usual

In treatment-experienced pediatric patients 4 weeks through 18 years of
age receiving ISENTRESS, the frequency, type and severity of
drug-related adverse reactions were comparable to those observed in

Grade 2–4 creatine kinase laboratory abnormalities were observed in
subjects treated with ISENTRESS. Myopathy and rhabdomyolysis have been
reported. Use with caution in patients at increased risk of myopathy or
rhabdomyolysis, such as patients receiving concomitant medications known
to cause these conditions and patients with a history of rhabdomyolysis,
myopathy or increased serum creatine kinase.

Rash occurred more commonly in treatment-experienced subjects receiving
regimens containing ISENTRESS + darunavir/ritonavir compared to subjects
receiving ISENTRESS without darunavir/ritonavir or darunavir/ritonavir
without ISENTRESS. However, rash that was considered drug related
occurred at similar rates for all 3 groups. These rashes were mild to
moderate in severity and did not limit therapy; there were no
discontinuations due to rash.

ISENTRESS should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. There are no adequate and
well-controlled studies in pregnant women. In addition, there have been
no pharmacokinetic studies conducted in pregnant patients.

To monitor maternal-fetal outcomes of pregnant patients exposed to
ISENTRESS, an Antiretroviral Pregnancy Registry has been established.
Physicians are encouraged to register patients by calling 1-800-258-4263.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies 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 health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
and connect with us on TwitterFacebookInstagram,
and LinkedIn.

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Please see Prescribing Information for ISENTRESS (raltegravir) at

Patient Information for ISENTRESS at

and Instructions for Use of ISENTRESS (raltegravir) for Oral Suspension

Pam Eisele, 267-305-3558
Carmen de Gourville, 267-305-4195
Teri Loxam, 908-740-1986
Amy Klug, 908-740-1898

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