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September 20, 2018 3:30 pm ET

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced that the Committee for Medicinal Products for Human Use
(CHMP) of the European Medicines Agency (EMA) has adopted a positive
opinion recommending granting of marketing authorization for two HIV-1
medicines: DELSTRIGO™, a once-daily fixed-dose combination tablet of
doravirine (100 mg), lamivudine (3TC, 300 mg) and tenofovir disoproxil
fumarate (TDF, 300 mg); and PIFELTRO™ (doravirine, 100 mg), a new
non-nucleoside reverse transcriptase inhibitor (NNRTI) to be
administered in combination with other antiretroviral medicines.
DELSTRIGO and PIFELTRO are currently under EMA review for the treatment
of adults with HIV-1 infection without past or present evidence of
resistance to the non-nucleoside reverse transcriptase class, lamivudine
or tenofovir. These two recommendations will now be reviewed by the
European Commission for marketing authorization in the European Union.
Marketing authorization applications for DELSTRIGO and PIFELTRO are also
under review in other countries, including Canada, Australia, and
Switzerland.

“We are pleased with the CHMP’s positive opinion recommending approval
of DELSTRIGO and PIFELTRO, which marks an important step forward in
advancing new treatments for people living with HIV,” said Dr. George
Hanna, vice president and therapeutic area head of infectious diseases,
Global Clinical Development, Merck Research Laboratories. “This
represents another milestone in Merck’s more than 30-year commitment to
HIV research and treatment, and advances our efforts to address the
unmet needs of the HIV community worldwide.”

The CHMP positive opinion was based on findings from two pivotal,
randomized, multicenter, double-blind, active controlled Phase 3 trials,
DRIVE-AHEAD and DRIVE-FORWARD, evaluating the efficacy and safety of
DELSTRIGO and PIFELTRO, respectively, in participants infected with
HIV-1 with no prior antiretroviral treatment history. In DRIVE-AHEAD,
DELSTRIGO demonstrated sustained viral suppression through 48 weeks,
meeting its primary endpoint of non-inferior efficacy compared to
efavirenz (EFV)/emtricitabine (FTC)/TDF. In DRIVE-FORWARD, PIFELTRO
demonstrated sustained viral suppression through 48 weeks, meeting its
primary endpoint of non-inferior efficacy compared to darunavir +
ritonavir, each in combination with FTC/TDF or abacavir (ABC)/3TC.

The U.S. Food and Drug Administration approved DELSTRIGO and PIFELTRO on
August 30, 2018. In the United States, both DELSTRIGO and PIFELTRO are
indicated for the treatment of HIV-1 infection in adult patients with no
prior antiretroviral treatment experience, and are administered orally
once daily with or without food. DELSTRIGO contains a boxed warning
regarding post-treatment acute exacerbations of hepatitis B (HBV)
infection. DELSTRIGO and PIFELTRO do not cure HIV-1 infection or AIDS.

Selected Safety Information about DELSTRIGO (doravirine/3TC/TDF) in
the U.S.

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 lamivudine 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 lamivudine.

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 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.

Selected Safety Information about PIFELTRO (doravirine) in the U.S.

PIFELTRO 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 PIFELTRO plasma concentrations
may occur, which may decrease the effectiveness of PIFELTRO. Immune
reconstitution syndrome can occur, including the occurrence of
autoimmune disorders with variable time to onset, which may necessitate
further evaluation and treatment. Co-administration of PIFELTRO with
efavirenz, etravirine or nevirapine is not recommended. If
co-administered with rifabutin, increase PIFELTRO dosage to one tablet
twice daily (approximately 12 hours apart).

Consult the full Prescribing Information prior to and during treatment
for important potential drug-drug interactions. The safety of PIFELTRO
is based on two studies, DRIVE-FORWARD and DRIVE-AHEAD. In
DRIVE-FORWARD, the most common adverse reactions (incidence ≥5%, all
intensities) were nausea (7%), headache (6%), fatigue (6%), diarrhea
(5%) and abdominal pain (5%). In DRIVE-AHEAD, the most common adverse
reactions (incidence ≥5%, all intensities) were dizziness (7%), abnormal
dreams (5%) and nausea (5%).

There is a pregnancy exposure registry that monitors pregnancy outcomes
in individuals exposed to PIFELTRO 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
PIFELTRO due to the potential for HIV transmission.

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
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Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., 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

Please see Prescribing Information for PIFELTRO (doravirine) at:

https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_pi.pdf

;

Patient Information for PIFELTRO (doravirine) at

https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_ppi.pdf

Merck
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Pamela Eisele, (267) 305-3558
Sarra S. Herzog, (908) 740-1871
or
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