Merck Announces Week 96 Data from Pivotal Phase 3 DRIVE-FORWARD Study of Its Investigational HIV Therapy Doravirine


July 24, 2018 5:45 am ET

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced Week 96 results from the Phase 3 DRIVE-FORWARD clinical
trial evaluating the efficacy and safety of doravirine (DOR), the
company’s investigational non-nucleoside reverse transcriptase inhibitor
(NNRTI), in combination with other antiretroviral agents, for the
treatment of HIV-1 infection in adult patients with no prior
antiretroviral treatment history (treatment-naïve). At Week 96, 73.1
percent (277/379) of the group treated with once-daily DOR achieved
viral suppression as measured by the proportion of patients who achieved
HIV-1 RNA of less than 50 copies/mL, compared to 66.0 percent (248/376)
of the group treated with once-daily ritonavir-boosted darunavir (DRV+r)
(treatment difference: 7.1%, 95% confidence interval: 0.5, 13.7). These
study results were presented today as a late-breaking abstract at the 22nd
International AIDS Conference
(AIDS 2018) taking place July 23-27,
2018, in Amsterdam.

Previously, the findings at Week 48 demonstrated that once-daily DOR met
its primary efficacy endpoint of non-inferiority compared to DRV+r, each
in combination with emtricitabine/tenofovir disoproxil fumarate
(FTC/TDF) or abacavir/lamivudine (ABC/3TC). These data were presented at
the Conference on Retroviruses and Opportunistic Infections in 2017.

“These Week 96 data reinforce the efficacy and safety of doravirine
found at 48 weeks, and support the potential use of doravirine in the
clinic as an important new treatment option for people living with
HIV-1,” said Professor Chloe Orkin, lead for HIV and HIV/Hep C research,
Ambrose King Centre, Royal London Hospital.


In DRIVE-FORWARD, 766 participants
(n=383 in each treatment group) with no antiretroviral treatment history
were randomized and received either DOR (100 mg) once daily or DRV+r
(800 mg and 100 mg, respectively) once daily, each in combination with
FTC/TDF or ABC/3TC selected by the investigator. In this trial, after 96
weeks of treatment, the proportion of participants achieving HIV-1 RNA
less than 50 copies/mL was 73.1 percent (277/379) in the DOR group and
66.0 percent (248/376) in the DRV+r group (treatment difference: 7.1%,
95% confidence interval: 0.5, 13.7). Results for participants with high
baseline viral load (HIV-1 RNA greater than 100,000 copies/mL) were 65.4
percent (51/78) for DOR and 65.2 percent (43/66) for DRV+r (treatment
difference: -1.1%, 95% confidence interval: -17.6, 15.3). In addition,
the mean change from baseline in CD4+ T-cell count at 96 weeks was 224
cells/mm3 for DOR and 207 cells/mm3 for DRV+r
(treatment difference: 17.4 cells/mm3, 95% confidence
interval: -14.5, 49.3). In terms of resistance, two participants in the
DOR treatment group (15 with successful genotype test) developed
genotypic and phenotypic resistance to DOR through 96 weeks of treatment.

The most common adverse events occurring in greater than or equal to 10
percent of participants in either treatment group through 96 weeks were
diarrhea (DOR 17.0% [65/383], DRV+r 23.8% [91/383]), nausea (DOR 11.7%
[45/383], DRV+r 13.6% [52/383]), headache (DOR 14.9% [57/383], DRV+r
12.0% [46/383]), upper respiratory tract infection (DOR 13.3% [51/383],
DRV+r 7.8% [30/383]), and viral upper respiratory tract infection (DOR
11.5% [44/383] and DRV+r 13.1% [50/383]). The rate of discontinuation of
therapy due to adverse events was 1.6 percent (6/383) in the DOR group
and 3.4 percent (13/383) in the DRV+r group.

At Week 96 mean changes from baseline in fasting serum blood lipids for
the DOR and DRV+r treated groups in levels of low density lipoprotein
cholesterol (LDL-C) were DOR -0.4 mg/dL and DRV+r 14.0 mg/dL (treatment
difference: -14.6, 95% confidence interval: -18.2, -11.0); and in
levels of non-high density lipoprotein cholesterol (non-HDL-C) were DOR
-0.5 mg/dL and DRV+r 17.7 mg/dL (treatment difference: -18.4, 95%
confidence interval: -22.5, -14.3). 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
4.1 mg/dL and 21.9 mg/dL (treatment difference: -18.1, 95% confidence
interval: -22.5, -13.7), 4.5 mg/dL and 4.2 mg/dL (treatment difference:
0.4, 95% confidence interval: -1.3, 2.1), and -1.1 mg/dL and 22.5 mg/dL
(treatment difference: -25.7, 95% confidence interval: -36.6, -14.7),

“For more than 30 years, Merck has advanced innovative science to help
change the trajectory in how HIV is treated. Today, our work is focused
on clinical research that is designed to truly address unmet patient
need,” said George Hanna, MD, vice president and therapeutic area head
of infectious diseases, global clinical development, Merck Research
Laboratories. “We are encouraged by the 96 Week results of the
DRIVE-FORWARD trial which support the efficacy and durability of
investigational NNRTI doravirine.”


DRIVE-FORWARD is a multicenter,
double-blind, randomized non-inferiority trial in which 766
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 FTC/TDF 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 efficacy at Week
96, 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
clinical trial registry number NCT02275780.

About Doravirine

Doravirine (DOR) is an investigational
NNRTI being evaluated by Merck for the treatment of HIV-1 infection. DOR
is being evaluated in several ongoing clinical trials both as a
once-daily single-entity tablet in combination with other antiretroviral
agents in a tailored regimen, and as a once-daily fixed-dose combination
(DOR/3TC/TDF) in a complete single tablet regimen. Phase 3 trials
include DRIVE-FORWARD, a trial comparing DOR to once-daily
ritonavir-boosted darunavir (DRV+r), each administered in combination
with FTC/TDF or ABC/3TC, in treatment-naïve adults; DRIVE-AHEAD, a trial
comparing DOR/3TC/TDF to efavirenz (EFV)/FTC/TDF in treatment-naïve
adults; and DRIVE-SHIFT, a trial evaluating a switch to DOR/3TC/TDF in
HIV-1 infected adults who are currently virologically suppressed on
another antiretroviral regimen. Other ongoing Phase 2 clinical trials
include an evaluation of DOR/3TC/TDF in treatment-naïve adults with
transmitted resistance to NNRTIs and in people switching from EFV due to

Earlier this year, the U.S. Food and Drug Administration (FDA) accepted
for review New Drug Applications for DOR and DOR/3TC/TDF for the
treatment of HIV-1 infection in treatment-naïve adults. The FDA has set
a target action date of October 23, 2018 for both applications.

Our Commitment to HIV

For more than 30 years, Merck has been
committed to scientific research and discovery in HIV and we continue to
be driven by the conviction that more medical advances are still to
come. Our focus is on pursuing research that addresses unmet medical
needs and helps people living with HIV and their communities. We are
making choices, including in our HIV pipeline, that could potentially
change the HIV treatment and prevention paradigms, and help bring us
closer to the goal of finding a cure. We remain committed to working
hand-in-hand with our partners in the global HIV community to address
the complex challenges to continued progress.

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
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Pam Eisele, 267-305-3558
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