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December 17, 2015 5:52 pm ET

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
announced today that the U.S. Food and Drug Administration (FDA) has
approved BRIDION^® (sugammadex) Injection 100 mg/mL
(equivalent to 108.8 mg/mL sugammadex sodium) for the reversal of
neuromuscular blockade (NMB) induced by rocuronium bromide and
vecuronium bromide in adults undergoing surgery.

BRIDION works differently than neostigmine, an agent used to reverse
non-depolarizing neuromuscular blocking agents (NMBAs) by increasing the
neurotransmitter acetylcholine at the neuromuscular junction. BRIDION
forms a complex with the non-depolarizing NMBAs rocuronium and
vecuronium, thereby removing these agents from the neuromuscular
junction and facilitating the return of muscle function. Unlike
neostigmine, BRIDION can be used to reverse different levels of
rocuronium and vecuronium-induced NMB, including deep block (1-2
post-tetanic counts [PTCs]).

“The FDA approval of BRIDION reflects Merck’s continued commitment to
develop medicines that address unmet needs,” said Dr. David Michelson,
vice president, Neurosciences, Merck Research Laboratories. “With
BRIDION, we now have a new option with a different mechanism of action
to reverse neuromuscular blockade induced by rocuronium and vecuronium
in adults undergoing surgery.”

BRIDION is contraindicated in patients with known hypersensitivity to
sugammadex or any of its components. Hypersensitivity reactions that
occurred varied from isolated skin reactions to serious systemic
reactions and have occurred in patients with no prior exposure to
sugammadex.

“Anesthesia professionals have a new option in the clinical care of
surgical patients,” said Dr. Ronald D. Miller, professor emeritus,
Department of Anesthesia & Perioperative Care, University of California,
San Francisco. “When surgical procedures end with patients in deep
block, as a result of rocuronium or vecuronium administration, BRIDION
provides a unique reversal option to restore neuromuscular function.”

BRIDION Clinical Studies

One hundred fifty-seven patients were evaluated in a phase 3,
multicenter, randomized, parallel-group, active-controlled safety
assessor-blinded clinical study. In the study, patients received either
rocuronium or vecuronium and underwent elective surgical procedures
under general anesthesia that required endotracheal intubation and
maintenance of neuromuscular blockade. At 1-2 PTCs (deep block), after
the last dose of rocuronium or vecuronium, 4 mg/kg BRIDION or 70 mcg/kg
neostigmine was administered. The time from the start of administration
of BRIDION or neostigmine to recovery of the train-of-four (T4/T1) ratio
of 0.9 was assessed. Generally, a T4/T1 ratio ≥0.9 correlates with
recovery from neuromuscular blockade. Neostigmine was not expected to
reverse neuromuscular blockade at a depth of 1-2 PTCs.

Patients treated with BRIDION achieved rapid recovery of neuromuscular
function from rocuronium-induced (n=37) deep block (1-2 PTCs) in a
median time of 2.7 minutes with a 25th and 75th percentiles of 2.1 and
4.3 minutes respectively, and from vecuronium-induced (n=47) deep block
in a median time of 3.3 minutes with a 25th and 75th percentiles of 2.3
and 6.6 minutes, respectively. There were 7 and 6 censored observations
in the rocuronium and vecuronium groups, respectively.

An additional phase 3, multicenter, randomized, parallel-group,
active-controlled safety assessor-blinded clinical study evaluated 189
patients who received either rocuronium or vecuronium and underwent
elective surgical procedures under general anesthesia that required
endotracheal intubation and maintenance of neuromuscular blockade. At
the reappearance of the second twitch (moderate block), after the last
dose of rocuronium or vecuronium, 2 mg/kg BRIDION or 50 mcg/kg
neostigmine was administered. The time from the start of administration
of BRIDION or neostigmine to recovery of the train-of-four (T4/T1) ratio
of 0.9 was assessed.

Patients treated with BRIDION (n=48) achieved faster recovery of
neuromuscular function from rocuronium-induced moderate block in a
median time of 1.4 minutes with a quartile 1 and quartile 3 of 1.2 and
1.7 minutes, respectively, versus a median time of 21.5 minutes with a
quartile 1 and quartile 3 of 9.8 and 42.0 minutes, respectively with
neostigmine (n=48). Reversal of vecuronium-induced moderate NMB with
BRIDION (n=48) occurred in a median time of 2.1 minutes with a quartile
1 and quartile 3 of 1.8 and 3.4 minutes, respectively, versus 29.0
minutes with a quartile 1 and quartile 3 of 12.2 and 76.2 minutes,
respectively with neostigmine (n=45).

Selected Safety Information about BRIDION

Potentially serious hypersensitivity reactions, including anaphylaxis,
have occurred in patients treated with BRIDION. In a clinical study,
anaphylaxis occurred in 0.3 percent (n=1/299) of healthy volunteers
treated with BRIDION. Observe patients for an appropriate period of time
after administration and take the necessary precautions. Anaphylaxis has
also been reported in the post-marketing setting. Clinical features in
anaphylaxis reports have included dermatologic symptoms; hypotension
often requiring the use of vasopressors; and prolonged hospitalization
and/or the use of additional respiratory support until full recovery.

Cases of marked bradycardia, some of which have resulted in cardiac
arrest, have been observed within minutes after the administration of
BRIDION. Monitor for hemodynamic changes and treat with anticholinergic
agents, such as atropine, if clinically significant bradycardia is
observed. Ventilatory support is mandatory for patients until adequate
spontaneous respiration is restored and the ability to maintain a patent
airway is assured. Should neuromuscular blockade persist after BRIDION
or recur following extubation, take appropriate steps to provide
adequate ventilation.

In clinical trials, a small number of patients experienced a delayed or
minimal response to BRIDION. Monitor ventilation until recovery occurs.

A minimum waiting time is necessary before re-administration of a
steroidal neuromuscular blocking agent after administration of BRIDION.
If neuromuscular blockade is required before the recommended waiting
time has elapsed, use a nonsteroidal neuromuscular blocking agent.

Due to the administration of BRIDION, certain drugs, including hormonal
contraceptives, could become less effective due to a lowering of the
(free) plasma concentrations. Consider re-administration of the other
drug, administration of a therapeutic equivalent drug, and/or
non-pharmacological interventions as appropriate.

Recurrence of neuromuscular blockade may occur due to displacement of
rocuronium or vecuronium from BRIDION by other drugs. Mechanical
ventilation may be required. Stop the administration of the drug which
caused displacement, if being administered by infusion.

The use of lower than recommended doses of BRIDION may lead to an
increased risk of recurrence of neuromuscular blockade and is not
recommended. Also, when drugs which potentiate neuromuscular blockade
are used in the post-operative phase, recurrence of neuromuscular
blockade is possible.

BRIDION doses of up to 16 mg/kg were associated with increases in
activated partial thromboplastin time and prothrombin time/international
normalized ratio. Carefully monitor coagulation parameters in patients
with known coagulopathies; being treated with therapeutic
anticoagulation; receiving thromboprophylaxis drugs other than heparin
and low molecular weight heparin; or receiving thromboprophylaxis drugs
and who then receive a dose of 16 mg/kg sugammadex.

BRIDION is not recommended for use in patients with severe renal
impairment, including those requiring dialysis. BRIDION also has not
been studied for reversal following rocuronium or vecuronium
administration in the ICU.

Do not use BRIDION to reverse nonsteroidal neuromuscular blocking agents
or steroidal neuromuscular blocking agents other than rocuronium or
vecuronium.

The most common adverse reactions (reported in ≥ 10% of patients at a 2,
4, or 16 mg/kg BRIDION dose and higher than placebo rate) were vomiting
(11 percent, 12 percent, or 15 percent versus placebo at 10 percent),
pain (48 percent, 52 percent, or 36 percent versus placebo at 38
percent), nausea (23 percent, 26 percent, or 23 percent versus placebo
at 23 percent), hypotension (4 percent, 5 percent, or 13 percent versus
placebo at 4 percent), and headache (7 percent, 5 percent, or 10 percent
versus placebo at 8 percent).

BRIDION Availability

BRIDION is expected to be available in January 2016.

About Merck

Today’s Merck is 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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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. 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 2014 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 BRIDION (sugammadex) Injection
at
http://www.merck.com/product/usa/pi_circulars/b/bridion/bridion_pi.pdf

Merck
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