First Patient Enrolled in New Phase 3 Trial Program Investigating a Once-Daily Dosing Regimen of ISENTRESS® (raltegravir)
June 5, 2014 4:00 pm ET
ONCEMRK Study Globally Enrolling Treatment-Naïve Adults with HIV-1
Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the first patient has been enrolled in the
company’s global Phase 3 clinical trial, ONCEMRK. ONCEMRK is assessing a
once-daily investigational formulation of ISENTRESS®
(raltegravir), known as reformulated raltegravir, as part of combination
HIV therapy for treatment-naïve HIV-1-infected adults. ISENTRESS
film-coated tablets are currently administered twice daily in accordance
with the approved Prescribing Information.
“ISENTRESS has been a significant component of first-line HIV-1
treatment for more than six years, as a twice-daily component of
antiretroviral therapy,” said Jürgen Rockstroh, M.D., University of
Bonn, Bonn-Venusberg, Germany, a clinical investigator on this study.
“We look forward to advancing our understanding of this new formulation
of once-daily raltegravir with this new trial.”
ISENTRESS is an integrase inhibitor indicated in combination with other
antiretroviral (ARV) agents for the treatment of HIV-1 infection in
patients four weeks of age and older. The use of other active agents
with ISENTRESS is associated with a greater likelihood of treatment
response. Severe, potentially life-threatening and fatal skin reactions
have been reported with ISENTRESS. Additionally, during the initial
phase of combination ARV treatment, immune reconstitution syndrome may
occur. (See Important Selected Safety Information below).
The ONCEMRK trial is a multicenter, double-blind, randomized,
active-controlled study evaluating the safety, efficacy, tolerability
and pharmacokinetics of reformulated raltegravir 1200 mg (dosed as two
600 mg tablets) once daily, compared with ISENTRESS 400 mg twice daily,
both in combination with once-daily tenofovir/emtricitabine over 96
weeks. The primary endpoint of the non-inferiority study is the
proportion of patients achieving viral suppression (<40 copies/mL) at
Week 48, which the company estimates will occur in the first half of
2016. Each patient in the study will receive treatment for approximately
96 weeks. To learn more about the ONCEMRK trial, contact Merck at
1-888-577-8839 or visit www.merck.com/clinical-trials.
Additional details can also be found online at www.clinicaltrials.gov/ct2/show/NCT02131233.
“We remain dedicated to investigating new applications for ISENTRESS and
to further expanding our knowledge of this HIV-1 treatment,” said Peter
Sklar, M.D., M.P.H., director, Clinical Research, Merck Research
Laboratories. “Merck is proud to mark this notable milestone in the
development of once-daily raltegravir and we look forward to continued
patient enrollment worldwide over the coming months.”
More than 160 centers in more than 25 countries are expected to
participate in the ONCEMRK trial in the coming months. Merck is planning
for the program to include approximately 750 patients worldwide.
Investigations of Raltegravir Once Daily
Reformulated raltegravir is a novel non-poloxamer based formulation.
Based on the results of several Phase 1 studies, reformulated
raltegravir has shown the potential to be investigated further for once
Data from the previous Phase 3 trial of raltegravir once daily, QDMRK,
have contributed to the understanding of raltegravir pharmacokinetics
and pharmacodynamics. QDMRK evaluated the long-term safety, tolerability
and efficacy of a once-daily 800 mg ISENTRESS dose in a combination
regimen compared with a twice-daily 400 mg ISENTRESS dose in
combination. The once-daily arm of QDMRK studied the ISENTRESS poloxamer
formulation given as two 400 mg tablets simultaneously. Results showed
the primary endpoint of non-inferiority was not met, with 83 percent of
treatment-naïve adult HIV-1 infected patients achieving viral
suppression (<50 copies/mL at Week 48) with the dosing regimen of 800 mg
raltegravir once daily, compared with 89 percent of patients treated
with ISENTRESS 400 mg twice daily. The safety and tolerability profiles
of the two regimens were generally similar in the study and similar to
the Prescribing Information for ISENTRESS.
Important Selected Safety Information
ISENTRESS does 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 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.
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 (UGT1A1) may result in
reduced plasma concentrations of raltegravir. Co-administration of
ISENTRESS with drugs that inhibit UGT1A1 may increase plasma levels of
raltegravir. Co-administration of ISENTRESS and other drugs may alter
the plasma concentration of raltegravir. The potential for drug-drug
interactions (DDIs) 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 coadministration 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%) drug-related clinical adverse reactions
of moderate to severe intensity in treatment-naïve adult patients
receiving ISENTRESS compared with efavirenz were insomnia (4% vs 4%),
headache (4% vs 5%), nausea (3% vs 4 %), fatigue (2% vs 3%), and
dizziness (2% vs 6%), respectively. In treatment-experienced adult
patients receiving ISENTRESS, the most commonly reported (≥2%)
drug-related clinical adverse reactions of moderate to severe intensity
and at a higher incidence compared with placebo was headache (2% vs
<1%). In both studies, intensities were defined as: Moderate (discomfort
enough to cause interference with usual activity); or Severe
(incapacitating with inability to work or do usual activity). 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 adults.
Grade 2 to 4 creatine kinase laboratory abnormalities were observed in
patients 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.
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 women. 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.
ISENTRESS is Merck’s integrase inhibitor for the treatment of HIV-1
infection in adult and pediatric patients ages 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 now
approved as part of combination therapy in more than 76 countries for
use in treatment-naïve adult patients with HIV-1 and in more than 114
countries for use in treatment-experienced adult patients with HIV-1.
ISENTRESS, in combination therapy, for use in children and adolescents
with HIV-1 ages two years and older has also been approved for use in 35
countries, and ISENTRESS oral suspension for infants at least four weeks
of age is approved for use in the U.S. Merck is continuing to move
forward with filings of ISENTRESS for oral suspension in additional
countries around the world.
To assist patients taking ISENTRESS, Merck offers the SUPPORT™ program,
which provides personal support and patient advocacy regarding
individual reimbursement issues. For more information about the SUPPORT™
program, please visit www.merckhelps.com
or call 1-800-850-3430.
Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside 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.merck.com
and connect with us on Twitter,
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 Merck’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; Merck’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 Merck’s patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.
Merck 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 Merck’s 2013 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) at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf
and Patient Information for ISENTRESS at http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_ppi.pdf.
ISENTRESS® is a registered trademark of
Merck & Co., Inc., Whitehouse Station, N.J., USA
Caroline Lappetito, 267-305-7639
Sarra Herzog, 908-423-6154
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088