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February 14, 2017 4:05 pm ET

Data Presented at CROI Showed Doravirine Was Non-inferior to Ritonavir-boosted Darunavir in Treatment-naïve Adults after 48 weeks of Treatment

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced results of a pivotal Phase 3 clinical trial evaluating
the safety and efficacy of doravirine (MK-1439), an investigational
non-nucleoside reverse transcriptase inhibitor (NNRTI). The study met
its primary efficacy endpoint of the proportion of participants
achieving levels of HIV-1RNA less than 50 copies/mL after 48 weeks of
treatment, demonstrating the non-inferiority of once-daily doravirine
(DOR) to once-daily ritonavir-boosted darunavir (DRV+r), each
administered with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)
or abacavir/lamivudine (ABC/3TC), in previously untreated
(treatment-naïve) adults with HIV-1 infection. In addition, a secondary
endpoint showed that the DOR-treated group had statistically significant
lower levels of fasting low density lipoprotein cholesterol (LDL-C),
versus the DRV+r group. Findings from the ongoing “DRIVE-FORWARD” Phase
3 trial following 48 weeks of treatment were presented as a
late-breaking abstract at the annual Conference on Retroviruses and
Opportunistic Infections (CROI) being held in Seattle from Feb. 13-16,
2017.

“Improved understanding of the biology of HIV and growing clinical
evidence from current therapies are advancing the management of HIV
infection,” said Dr. Kathleen Squires, professor and director of
infectious diseases, Thomas Jefferson University, Philadelphia. “The
results of this study provide solid evidence of the efficacy and safety
profile of doravirine as a potential treatment option for
treatment-naïve HIV-1 patients.”

Data from DRIVE- FORWARD

In the trial, after 48 weeks of treatment, the proportion of
participants achieving levels of HIV-1 RNA less than 50 copies/mL
following once-daily DOR (100 mg) or once-daily DRV+r (800 mg and 100 mg
respectively), each in combination with either TDF/FTC or ABC/3TC, was
83.8 percent (321/383) and 79.9 percent (306/383), respectively; with a
treatment difference (95 % confidence interval) of 3.9 [-1.6, 9.4].
Increases in mean CD4+ T-cell counts from baseline were similar for the
DOR and DRV+r treatment groups: 193 and 186 cells/mm³,
respectively.

In addition, comparable efficacy was observed for participants with
baseline levels of HIV-1 RNA greater than 100,000 copies/mL: 81.0
percent (64/79) for DOR and 76.4 percent (55/72) for DRV+r; with a
treatment difference (95% confidence interval) of 3.0 [-11.2, 17.1]. One
out of 383 participants developed phenotypic and genotypic resistance in
the DOR arm (the patient came off study at Week 24 because of
non-adherence). None of the 383 participants receiving DRV+r developed
phenotypic and genotypic resistance.

The rates of reported adverse drug reactions were 31 percent (117/383)
for DOR and 32 percent (123/383) for DRV+r. Discontinuations due to
adverse events for the DOR and DRV+r treatment groups were 2 percent
(6/383) and 3 percent (12/383), respectively. The most common adverse
events for DOR and DRV+r (occurring in greater than or equal to 10
percent of participants) were: diarrhea (14% vs. 22%); headache (14% vs.
11%); nausea (11% vs. 12%) and nasopharyngitis (8% vs. 10 %),
respectively.

Analysis of fasting serum blood lipids for the DOR and DRV+r treated
groups showed a statistically significant difference (p<0.0001) in mean
changes from baseline in the levels of LDL-C (-4.5 mg/dL vs. +9.9 mg/dL)
and non-high density lipoprotein cholesterol (non-HDL-C) (-5.3 mg/dL vs.
+13.8 mg/dL), respectively. Mean changes from baseline in total
cholesterol, high density lipoprotein cholesterol (HDL-C) and
triglycerides for the DOR- treated group and the DRV+r- treated group
were -1.4 mg/dL, +3.9 mg/dL, and -3.1 mg/dL vs. +17.9 mg/dL, +4.2 mg/dL,
and +22 mg/dL, respectively.

“Merck has been at the forefront of research into HIV for three
decades,” said Dr. George Hanna, associate vice president, clinical
research, Merck Research Laboratories. “We are encouraged by these
results, which provide additional insights into the efficacy and safety
of doravirine.”

About DRIVE-FORWARD

DRIVE-FORWARD is a multicenter, double-blind, randomized non-inferiority
trial in which 769 treatment-naïve adults with HIV-1 infection received
either 100 mg doravirine or 800 mg darunavir plus 100 mg ritonavir, both
administered orally once-daily in combination with either TDF/FTC or
ABC/3TC. The primary endpoint of the clinical trial was the proportion
of participants with HIV-1 RNA copies of less than 50 copies/mL at Week
48. There were a number of secondary endpoints, including an evaluation
of the effects of DOR and DRV+r on fasting serum lipids, change from
baseline in CD4+ T-cell count, and evaluation of safety and tolerability.

For further information regarding DRIVE-FORWARD please visit www.clinicaltrials.gov

clinical trial registry number NCT02275780.

About Doravirine

Doravirine is an investigational NNRTI being evaluated by Merck for the
treatment of HIV-1 infection. In early clinical studies, doravirine
demonstrated a pharmacokinetic profile supportive of once-daily dosing
and the ability to be dosed with or without food.

Doravirine is also being evaluated in several ongoing studies as a fixed
dose single tablet regimen with 3TC and TDF (DOR/3TC/TDF). Phase 2
studies include an evaluation of DOR/3TC/TDF in treatment-naïve
participants with transmitted resistance to NNRTIs and in people
switching from efavirenz due to intolerability. Phase 3 studies include
DRIVE-AHEAD, a trial comparing DOR/3TC/TDF to efavirenz/ FTC/TDF in
treatment-naïve participants, and DRIVE-SHIFT, a trial evaluating a
switch to DOR/3TC/TDF in people who are currently virologically
suppressed on another antiretroviral regimen.

About Merck

For over a century, Merck has been a global health care 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
health care through far-reaching policies, programs, and partnerships.
For more information, visit www.merck.com
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