Merck Announces Data from 48-Week Phase 2b Study of Investigational HIV Therapy Doravirine (MK-1439) in Treatment-Naive Patients


November 3, 2014 5:00 am ET

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

“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

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

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,
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Pamela Eisele, 267-305-3558
Carmen de Gourville, 267-664-0146
Joseph Romanelli, 908-423-5185
Justin Holko, 908-423-5088

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