Phase 3 Clinical Trial Enrollment Scheduled
to Start by the End of 2014
Merck (NYSE:MRK), known as MSD outside the United States and
Canada, today announced the presentation of results from a Phase 2b
clinical trial evaluating the safety and efficacy of once-daily
oral doravirine, an investigational next-generation non-nucleoside
reverse transcriptase inhibitor (NNRTI), plus
tenofovir/emtricitabine (TDF/FTC) compared to efavirenz plus
TDF/FTC in previously untreated patients with HIV-1 infection.
Results were presented as a poster (#0434) and oral presentation by
Dr. Josep M. Gatell, head, Infectious Diseases and AIDS
Units-IDIBAPS, Hospital Clinic, Barcelona, at the 12th
International Congress on HIV Drug Therapy being held in Glasgow,
United Kingdom, Nov. 2-6.
The primary safety analysis from the expansion phase of the
study compared the incidence of central nervous system (CNS)
adverse events (AEs) by Week 8 in patients who received doravirine
100 mg plus TDF/FTC (n=108) versus patients who received efavirenz
with TDF/FTC (n=108). The results showed a significantly lower
incidence of one or more of reported CNS AEs (all causality) among
the doravirine-treated group compared to the efavirenz-treated
group (22.2 % vs. 43.5 %, respectively; p<0.001). The most
common (occurring in more than 5 percent of patients) CNS AEs in
the doravirine-and efavirenz-treated groups, respectively, were
dizziness (9.3 % vs. 27.8 %), insomnia (6.5 % vs. 2.8 %), abnormal
dreams (5.6 % vs. 16.7 %) and nightmares (5.6 % vs. 8.3 %).
Interim results for this ongoing Phase 2b study, including the
primary efficacy analysis for dose selection based on 24-week data
from the dose-ranging cohort of the study, were previously
presented at the 21st Conference on Retroviruses and
Opportunistic Infections (CROI) in March 2014.
“This program underscores Merck’s ongoing commitment to the
research and development of new therapeutic options for patients
with HIV,” said Dr. Hedy Teppler, executive director, Infectious
Diseases, Merck Research Laboratories. “We are encouraged by the
antiviral activity and the overall tolerability profile of
doravirine and look forward to initiating Phase 3 studies.”
Additional follow-up data through 48 weeks of treatment showed a
76 percent (n=126/166) overall virologic response rate (HIV RNA
<40 c/ml) for all doravirine doses (25, 50, 100 and 200 mg) that
is comparable to 71 percent (n=30/42) reported for patients
administered efavirenz (600 mg). In addition, all treatment groups
showed increased CD4 cell counts relative to baseline, consistent
with the 24-week findings.
After 48 weeks of treatment, patients in the dose ranging part
of the study who received doravirine demonstrated a lower overall
incidence of drug-related adverse events (36.7%; n=166) than those
who received efavirenz (57.1%; n=42). The most commonly reported
drug-related clinical adverse events in the doravirine and
efavirenz groups respectively were abnormal dreams (10.2% vs.
9.5%); nausea (7.8% vs. 2.4%); fatigue (7.2% vs. 4.8%); diarrhea
(4.8% vs. 9.5%) and dizziness (3.0% vs. 23.8%). Doravirine-treated
patients also had a lower incidence of laboratory abnormalities in
routine clinical tests including increased total cholesterol (6.8%
for doravirine vs. 31.6% for efavirenz) and LDL cholesterol (6.3%
for doravirine vs. 18.4% for efavirenz).
Merck plans to initiate the first Phase 3 clinical trial of
doravirine by the end of 2014, NCT02275780. The study will enroll
treatment-naïve patients and compare the efficacy, safety and
tolerability of doravirine and ritonavir-boosted darunavir, both in
combination with other anti-retroviral therapy.
About the Phase 2b Study
The Phase 2b randomized, double blind, dose-ranging clinical
trial (NCT01632345) evaluated the efficacy, safety and tolerability
of once-daily doravirine (25, 50, 100 and 200 mg) compared to
once-daily efavirenz 600 mg, both in combination with TDF/FTC, in
previously untreated HIV-1 infected patients. The study has two
parts:
- In Part 1, the dose-ranging phase,
patients received once daily doravirine (N=166) at one of four
doses (25, 50, 100 or 200 mg) or efavirenz (n=42), both in
combination with TDF/FTC. The doravirine dose to be used in Part 2
of the Phase 2b study and in Phase 3 was selected based on the Week
24 safety and efficacy data in doravirine-treated patients. After
dose selection, all doravirine-treated patients were switched to
the selected dose (100 mg doravirine) for the expansion phase of
the study.
- In Part 2, the expansion phase, an
additional 132 patients were enrolled to receive 100 mg doravirine
(n=66) or efavirenz (n=66), both in combination with TDF/FTC, to
enable an assessment of the CNS safety and tolerability profile of
doravirine.
The planned total treatment duration in the Phase 2 study is 96
weeks.
About Doravirine
Doravirine, also known as MK-1439, is an investigational
next-generation, NNRTI being developed by Merck for the treatment
of HIV-1 infection. In preclinical studies, doravirine showed
potent antiviral activity against HIV-1. In early clinical studies,
doravirine demonstrated a pharmacokinetic profile supportive of a
once-daily dosing schedule and did not show a significant food
effect.
Merck’s Commitment to HIV
For more than 25 years, Merck has been at the forefront of the
response to the HIV epidemic, and has helped to make a difference
through our proud legacy of commitment to innovation, collaboration
with the community, and expanding global access to medicines. Merck
is dedicated to applying our scientific expertise, resources and
global reach to deliver healthcare solutions that support people
living with HIV worldwide.
About Merck
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 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, Facebook and YouTube.
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Private Securities Litigation Reform Act of 1995. These statements
are based upon the current beliefs and expectations of Merck’s
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the products will receive the necessary regulatory approvals or
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approval; Merck’s ability to accurately predict future market
conditions; manufacturing difficulties or delays; financial
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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.
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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
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MerckMedia:Pamela Eisele, 267-305-3558orCarmen de Gourville,
267-664-0146orInvestors:Joseph Romanelli, 908-423-5185orJustin
Holko, 908-423-5088
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