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October 4, 2018 5:45 am ET

New Data on Patients Who Were Virologically Suppressed Switching to DELSTRIGO to be Presented as Late-Breaker Oral Presentation at IDWeek 2018

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced the first presentation of data from the Phase 3
DRIVE-SHIFT trial evaluating a switch of medication to DELSTRIGO™, a
once-daily fixed-dose combination tablet of doravirine (100 mg),
lamivudine (3TC, 300 mg) and tenofovir disoproxil fumarate (TDF, 300
mg), in adults with HIV-1 infection who demonstrated virological
suppression for at least six months on a stable antiretroviral treatment
regimen. The study met its primary endpoint of non-inferior efficacy as
measured by the proportion of participants who switched to DELSTRIGO and
had plasma HIV-1 RNA levels <50 copies/mL at Week 48 compared to the
proportion of participants who continued on their baseline regimen and
had HIV-1 RNA levels <50 copies/mL at Week 24. These study results will
be presented today as a late-breaking oral presentation at
IDWeek
2018
taking place Oct. 3-7, 2018, in San Francisco.

“These data build on the existing clinical profile of DELSTRIGO as seen
in treatment-naïve patients, and suggests its potential to address a
broader population,” said Dr. Princy Kumar, Chief, Division of
Infectious Diseases and Tropical Medicine at MedStar Georgetown
University Hospital and Professor of Medicine and Microbiology,
Georgetown University School of Medicine, Washington, D.C. “Data from
this trial support another possible future option for people living with
HIV, many of whom may require a change to a different treatment regimen.”

Data from DRIVE-SHIFT

In the DRIVE-SHIFT study, 670 participants who demonstrated virological
suppression (undetectable HIV-1 RNA) on an antiretroviral regimen for at
least six months were randomized to begin treatment with DELSTRIGO
(doravirine/3TC/TDF) immediately on Day 1 (immediate switch group, ISG;
N=447) or after 24 weeks (delayed switch group, DSG; N=223). The primary
endpoint was the proportion of participants with HIV-1 RNA <50
copies/mL, with the primary comparison between the DELSTRIGO ISG at Week
48 and baseline regimen DSG at Week 24, and a secondary comparison
between the DELSTRIGO ISG and baseline regimen DSG at Week 24.

In the study, DELSTRIGO-receiving participants in the ISG maintained
virologic control at the 48-week timepoint:

• 90.8 percent (406/447) of participants who switched to DELSTRIGO on
  Day 1 (ISG) had HIV-1 RNA <50 copies/mL at Week 48; in comparison,
  94.6 percent (211/223) of participants who continued on their baseline
  regimen (DSG) had HIV-1 RNA <50 copies/mL at Week 24 (treatment
  difference: -3.8%, 95% confidence interval: -7.9, 0.3).
• 1.6 percent in the DELSTRIGO ISG group had HIV-1 RNA ≥50 copies/mL at
  Week 48 compared to 1.8 percent in the baseline regimen DSG group at
  Week 24 (treatment difference: -0.2%, 95% confidence interval: -2.5,
  2.1).

Secondary comparisons were also made at Week 24 for both treatment
groups. DELSTRIGO-receiving participants in the ISG also maintained
virologic control at this earlier (Week 24) timepoint:

• 93.7 percent (419/447) of participants who switched to DELSTRIGO on
  Day 1 (ISG) had HIV-1 RNA <50 copies/mL, compared with 94.6 percent
  (211/223) of those who continued on their baseline regimen (DSG)
  (treatment difference: -0.9%; 95% confidence interval: -4.7, 3.0).
• 1.8 percent in both treatment groups had HIV-1 RNA ≥50 copies/mL at
  Week 24 (treatment difference: 0.0%; 95% confidence interval: -2.3,
  2.3).

No genotypic or phenotypic resistance to any study drug was observed in
participants taking DELSTRIGO through 48 weeks of treatment.

At Week 24, participants who switched to DELSTRIGO on Day 1 showed
statistically significant decreases in fasting LDL-cholesterol (LDL-C)
and non-HDL-cholesterol (non-HDL-C) compared to those who continued on a
boosted protease inhibitor regimen (LDL-C: -16.5 mg/dL vs. -1.9 mg/dL,
treatment difference: -14.7, 95% confidence interval: -18.9, -10.4,
p<0.0001; non-HDL-C: -24.7 mg/dL vs. -1.3 mg/dL, treatment difference:
-23.0, 95% confidence interval: -28.0, -18.1, p<0.0001). At this
timepoint, DELSTRIGO (doravirine/3TC/TDF) also showed decreases in
cholesterol and triglyceride levels (cholesterol: -26.2 mg/dL vs. 0.5
mg/dL, treatment difference: -25.8, 95% confidence interval: -31.0,
-20.7; triglycerides: -43.2 mg/dL vs. 0.9 mg/dL, treatment difference:
-42.9, 95% confidence interval: -59.1, -26.7).

The most common adverse events (>5% incidence in any group) in the
DELSTRIGO ISG group through Week 24, the baseline regimen DSG group
through Week 24, and the DSG group after the delayed switch to DELSTRIGO
(Week 24 to Week 48) were nasopharyngitis (7.4%; 5.4%; 4.3%,
respectively) and headache (6.5%; 2.2%; 6.7%, respectively). The most
common drug-related adverse event (>2% incidence in any group) was
headache (1.6%; 0.4%; 2.4%, respectively). The rates of discontinuation
of therapy due to adverse events through Week 24 were 2.5% in the
DELSTRIGO ISG group and 0.4% in the baseline regimen DSG group.

“Merck’s dedication over the past several decades to improving HIV
treatment and care has always been focused on addressing unmet needs.
People living with HIV need new treatment options,” said Dr. George
Hanna, vice president and therapeutic area head of infectious diseases,
global clinical development, Merck Research Laboratories. “The data from
DRIVE-SHIFT suggest the clinical potential of DELSTRIGO to serve as a
new fixed-dose combination option for those considering a change in
their HIV antiretroviral treatment regimen.”

About DRIVE-SHIFT

DRIVE-SHIFT is a Phase 3 multicenter, open-label, randomized,
active-controlled, non-inferiority clinical trial evaluating a switch to
DELSTRIGO compared with continuation of current therapy in adults with
HIV-1 infection who were virologically suppressed (undetectable plasma
HIV-1 RNA levels <40 copies/mL) for at least six months on a stable
regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) plus
a boosted protease inhibitor, boosted elvitegravir, or NNRTI.
Participants with screening HIV-1 RNA <40 copies/mL, no history of
virologic failure on any regimen, and no resistance to DELSTRIGO were
randomized (2:1) to start DELSTRIGO on Day 1 (ISG) or after 24 weeks
(DSG). The primary endpoint was the proportion of participants with
HIV-1 RNA <50 copies/mL, with the primary comparison between the
DELSTRIGO ISG at Week 48 and baseline regimen DSG at Week 24 and a
secondary comparison between the treatment groups at Week 24. For
further information regarding DRIVE-SHIFT please visit www.clinicaltrials.gov
clinical trial registry number NCT02397096.

On Aug. 30, 2018, DELSTRIGO (doravirine/3TC/TDF) was approved by the
U.S. Food and Drug Administration for the treatment of HIV-1 infection
in adult patients with no prior antiretroviral treatment experience and
is administered orally once daily with or without food. In the U.S.,
DELSTRIGO contains a boxed warning regarding post-treatment acute
exacerbation of hepatitis B (HBV) infection. DELSTRIGO does not cure
HIV-1 infection or AIDS. On Sept. 20, 2018, the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency (EMA)
adopted a positive opinion recommending granting of marketing
authorization for DELSTRIGO.

Selected Safety Information about DELSTRIGO (doravirine/3TC/TDF)

Warning: Post treatment Acute Exacerbation of Hepatitis B (HBV)

All patients with HIV-1 should be tested for the presence of HBV before
initiating antiretroviral therapy. Severe acute exacerbations of HBV
have been reported in patients who are coinfected with HIV-1 and HBV and
have discontinued products containing 3TC or TDF, which are components
of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue
DELSTRIGO should be monitored with both clinical and laboratory
follow-up for at least several months after stopping DELSTRIGO. If
appropriate, initiation of anti-HBV therapy may be warranted.

DELSTRIGO is contraindicated when co-administered with drugs that are
strong cytochrome P450 (CYP)3A enzyme inducers (including the
anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and
phenytoin; the androgen receptor inhibitor enzalutamide; the
antimycobacterials rifampin and rifapentine; the cytotoxic agent
mitotane; and the herbal product St. John’s wort (Hypericum perforatum)),
as significant decreases in doravirine plasma concentrations may occur,
which may decrease the effectiveness of DELSTRIGO. DELSTRIGO is
contraindicated in patients with a previous hypersensitivity reaction to
3TC.

Renal impairment, including cases of acute renal failure and Fanconi
syndrome, have been reported with the use of TDF. DELSTRIGO should be
avoided with concurrent or recent use of a nephrotoxic agent, as cases
of acute renal failure after initiation of high-dose or multiple NSAIDs
have been reported in patients with risk factors for renal dysfunction
who appeared stable on TDF.

Prior to or when initiating DELSTRIGO, and during treatment, assess
serum creatinine, estimated creatinine clearance, urine glucose and
urine protein in all patients. In patients with chronic kidney disease,
also assess serum phosphorus. Discontinue DELSTRIGO in patients who
develop clinically significant decreases in renal function or evidence
of Fanconi syndrome. Discontinue DELSTRIGO (doravirine/3TC/TDF) if
estimated creatinine clearance declines below 50 mL/min.

In clinical trials in HIV-1 infected adults, TDF was associated with
slightly greater decreases in bone mineral density (BMD) and increases
in biochemical markers of bone metabolism. Serum parathyroid hormone
levels and 1,25 vitamin D levels were also higher. Cases of osteomalacia
associated with proximal renal tubulopathy have been reported with the
use of TDF.

Immune reconstitution syndrome can occur, including the occurrence of
autoimmune disorders with variable time to onset, which may necessitate
further evaluation and treatment. Because DELSTRIGO is a complete
regimen, co-administration with other antiretroviral medications for the
treatment of HIV-1 infection is not recommended.

Consult the full Prescribing Information prior to and during treatment
for important potential drug-drug interactions.

If co-administered with rifabutin, take one tablet of DELSTRIGO once
daily, followed by one tablet of doravirine (PIFELTRO) approximately 12
hours after the dose of DELSTRIGO. The most common adverse reactions
with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%),
nausea (5%) and abnormal dreams (5%).

There is a pregnancy exposure registry that monitors pregnancy outcomes
in individuals exposed to DELSTRIGO during pregnancy. Healthcare
providers are encouraged to register patients by calling the
Antiretroviral Pregnancy Registry at 1-800-258-4263. Mothers infected
with HIV-1 should be instructed not to breastfeed if they are receiving
DELSTRIGO due to the potential for HIV-1 transmission. Because DELSTRIGO
is a fixed-dose combination tablet and the components cannot be altered,
it is not recommended in patients with estimated creatinine clearance
less than 50 mL/min.

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 remain committed to working hand-in-hand
with our partners in the global HIV community to address the complex
challenges to continuing 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 more information, visit www.merck.com and connect
with us on Twitter,
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YouTube
and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, NJ, USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’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; the company’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 the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company 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 the company’s 2017 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 DELSTRIGO (doravirine/3TC/TDF)
at: 

https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_pi.pdf

Patient Information for DELSTRIGO (doravirine/3TC/TDF) at: 

https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_ppi.pdf

For Merck
Media:
Pam Eisele, 267-305-3558
or
Sarra S. Herzog, 201-669-6570
or
Investors:
Teri Loxam, 908-740-1986
or
Michael DeCarbo, 908-740-1807