Merck Announces Week 96 Results from ONCEMRK, A Study Evaluating Once-Daily ISENTRESS® HD (raltegravir), in Combination with Other Antiretroviral Agents, for the Treatment of HIV-1 Infection in Appropriate Patients

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July 24, 2017 6:00 am ET

Once-Daily Version of Raltegravir Now Approved in U.S. and European Union

Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced the presentation of Week 96 results from the pivotal
Phase 3 ONCEMRK study evaluating the efficacy and safety of ISENTRESS HD1,
a 1200 mg once-daily dose of the company’s integrase inhibitor, ISENTRESS®
(raltegravir), administered orally as two 600 mg film-coated tablets, in
combination with other antiretroviral agents, for the treatment of HIV-1
infection in adults and pediatric patients weighing at least 40 kg, who
are treatment-naïve or whose virus has been suppressed on an initial
regimen of ISENTRESS 400 mg given twice daily. Previously, the findings
at Week 48 demonstrated that once-daily ISENTRESS HD met its primary
efficacy endpoint of non-inferiority to twice-daily ISENTRESS, with a
similar safety and tolerability profile. The Week 96 results reaffirm
the comparable efficacy and safety of ISENTRESS HD. These study results
were presented today during a late-breaking abstract session at the 9th
International Conference on HIV Science (IAS
2017
) being held in Paris, France, from July 23-26, 2017.

“The Week 96 results from the ONCEMRK trial reinforce the findings from
the 48-week analysis and support the use of ISENTRESS HD, in combination
with other antiretroviral agents, as a once-a-day treatment option for
some people living with HIV,” said Dr. Pedro Cahn, chief of the
infectious disease unit at Juan A. Fernandez Hospital, Buenos Aires,
Argentina, and lead study investigator.

ISENTRESS and ISENTRESS HD do not cure HIV-1 infection or AIDS. 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 or ISENTRESS HD and other suspect
agents if severe hypersensitivity, severe rash, or rash with systemic
symptoms or liver aminotransferase elevations develop and monitor
clinical status, including liver aminotransferases closely. For more
information, see “Selected Safety Information” below.

Week 96 data from the ONCEMRK study showed that 81.5 percent of the 531
patients taking once-daily ISENTRESS HD 1200 mg (2 x 600 mg) achieved
viral suppression of less than 40 copies/mL of HIV-1 RNA, compared to
80.1 percent of the 266 patients taking twice-daily ISENTRESS 400 mg,
both in combination therapy with emtricitabine plus tenofovir disoproxil
fumarate, with a treatment difference of 1.4 percent (95 percent
confidence interval -4.4, 7.3). Increases in CD4+T-cell counts from
baseline were comparable for the two treatment regimens, with an average
increase of 261.6 cells/mm3 for once-daily ISENTRESS HD and
262.2 cells/mm3 for twice-daily ISENTRESS. Efficacy was
consistent across a variety of patient populations, including those with
high viral load at baseline (HIV-1 RNA >100,000 copies/mL).

Treatment-emergent viral mutations leading to any drug resistance were
detected in less than 1 percent of patients in both treatment arms, with
4/531 (0.8 percent) in the once-daily ISENTRESS HD treatment arm, and
2/266 (0.8 percent) in the twice-daily ISENTRESS treatment arm through
96 weeks. The rate of discontinuation of therapy due to adverse events
through 96 weeks was low (1.3 percent in patients receiving once-daily
ISENTRESS HD and 2.3 percent in patients receiving twice-daily
ISENTRESS).

In the United States, once-daily ISENTRESS HD was approved by the Food
and Drug Administration (FDA) on May 26, 2017, in combination with other
antiretroviral agents, for the treatment of HIV-1 infection in adults,
and pediatric patients weighing at least 40 kg, who are treatment-naïve
or whose virus has been suppressed on an initial regimen of ISENTRESS
400 mg given twice daily. ISENTRESS HD is administered as a 1200 mg
once-daily dose, given orally as two 600 mg film-coated tablets.

On July 13, 2017, the European Commission granted marketing
authorization for once-daily ISENTRESS 600 mg in the European Union, to
be administered as a once-daily 1200 mg oral dose given as two 600 mg
tablets, in combination therapy with other antiretroviral medicinal
products, for the treatment of HIV-1 infection in adults and pediatric
patients weighing at least 40 kg, who are treatment-naïve or whose virus
has been suppressed on an initial regimen of ISENTRESS 400 mg twice
daily. Regulatory reviews are underway for once-daily version of
ISENTRESS in other countries and regions around the world, including
Australia and Switzerland.

About ONCEMRK

The ONCEMRK study is a Phase 3 multicenter, double-blind, randomized,
active comparator-controlled clinical trial designed to evaluate the
efficacy and safety of once-daily ISENTRESS HD 1200 mg (given as two 600
mg oral tablets), compared to twice-daily ISENTRESS 400 mg, each in
combination therapy with emtricitabine plus tenofovir disoproxil
fumarate in previously untreated adults with HIV-1 infection with levels
of HIV-1 RNA ≥ 1,000 copies/mL. The primary efficacy objective was the
proportion of participants achieving less than 40 copies/mL of HIV-1 RNA
at Week 48, with a planned total treatment duration of 96 weeks. The
non-inferiority margin was 10 percentage points.

Selected Safety Information about ISENTRESS HD (raltegravir) and
ISENTRESS (raltegravir)

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

Co-administration of ISENTRESS or ISENTRESS HD 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 or ISENTRESS HD is not
recommended. Co-administration of ISENTRESS HD with calcium carbonate
antacids, tipranavir/ritonavir, or etravirine is also not recommended.

During co-administration with rifampin, the recommended dosage of
ISENTRESS in adults is 800 mg twice daily. Rifampin, a strong inducer of
UGT1A1, reduces plasma concentrations of ISENTRESS. There are no data to
guide co-administration of ISENTRESS with rifampin in patients below 18
years of age.

Co-administration with rifampin is not recommended with ISENTRESS HD.

The impact of other strong inducers of drug metabolizing enzymes on
raltegravir is unknown (e.g., Carbamazepine, Phenobarbital, and
Phenytoin). Co-administration of ISENTRESS or ISENTRESS HD with other
strong inducers is not recommended.

About ISENTRESS (raltegravir)

Approved in 2007, ISENTRESS was the first integrase inhibitor developed
for the treatment of HIV-1 infection. ISENTRESS is one of the
regimen options recommended by the Department of Health and Human
Services – in combination with other antiretroviral agents – as a
first-line therapy in treatment-naïve HIV-1 infected adults. ISENTRESS
chewable tablets and oral suspension, each in combination therapy, are
approved to treat pediatric patients aged at least four weeks of age,
and weighing less than 20 kg.

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 adult patients. ISENTRESS, 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 oral suspension for infants at least four weeks of age is
approved for use in 33 countries.

Selected Safety Information about ISENTRESS HD (raltegravir) and
ISENTRESS (raltegravir) Continued

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 headache (4
percent vs. 5 percent), insomnia (4 percent vs. 4 percent), nausea (3
percent vs. 4 percent), dizziness (2 percent vs. 6 percent), and fatigue
(2 percent vs. 3 percent), respectively. The most commonly reported (≥2
percent) clinical adverse reactions of all intensities (Mild, Moderate,
and Severe) in treatment-naïve adult patients receiving ISENTRESS HD
compared with ISENTRESS through 48 weeks included abdominal pain,
diarrhea, vomiting, and decreased appetite. Intensities were defined as
follows: Mild (awareness of sign or symptom, but easily tolerated);
Moderate (discomfort enough to cause interference with usual activity);
or Severe (incapacitating with inability to work or do usual activity).

Grade 2–4 creatine kinase laboratory abnormalities were observed in
subjects treated with ISENTRESS or ISENTRESS HD. Myopathy and
rhabdomyolysis have been reported with ISENTRESS. 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.

There is a pregnancy exposure registry that monitors pregnancy outcomes
in women exposed to ISENTRESS or ISENTRESS HD during pregnancy.
Healthcare providers are encouraged to register patients by calling the
Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.

Women infected with HIV-1 should be instructed not to breastfeed if they
are receiving ISENTRESS or ISENTRESS HD due to the potential for HIV
transmission.

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,
visit www.merck.com
and connect with us on TwitterFacebookInstagram,
YouTube
and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’s management and are subject to
significant risks and uncertainties. There can be no guarantees with
respect to pipeline products that the products will receive the
necessary regulatory approvals or that they will prove to be
commercially successful. 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; the company’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 the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’s 2016 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).

Please see Prescribing Information for ISENTRESS (raltegravir) and
ISENTRESS HD (raltegravir) at


http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf

,
Patient Information for ISENTRESS and ISENTRESS HD (raltegravir) at



http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ppi.pdf

.
The Instructions for Use also are available at


http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ifu.pdf

1 ISENTRESS HD is marketed outside of the U.S. as ISENTRESS
600 mg



Merck
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or
Carmen de Gourville, 267-664-0146
or
Investors:
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or
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