Merck Announces FDA Acceptance of Resubmission of New Drug Application for Sugammadex Sodium Injection

  Merck Announces FDA Acceptance of Resubmission of New Drug Application for
  Sugammadex Sodium Injection

Business Wire

WHITEHOUSE STATION, N.J. -- January 7, 2013

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today
announced that the resubmission of the New Drug Application (NDA) for
sugammadex sodium injection has been accepted for review by the U.S. Food and
Drug Administration (FDA). Merck expects the FDA’s review to be completed in
the first half of 2013.

Sugammadex sodium injection is the company's investigational agent for the
reversal of neuromuscular blockade (NMB) induced by rocuronium or vecuronium
(neuromuscular blocking agents). NMB is used in anesthesiology to induce
muscle relaxation during surgery. Sugammadex is designed to work by
inactivating rocuronium or vecuronium molecules directly by encapsulation. If
approved, it would be the first in a new class of medicines in the U.S. known
as selective relaxant binding agents to be used in the surgical setting.

In 2008, the FDA did not approve the original NDA for sugammadex sodium
injection, requesting additional data related to hypersensitivity (allergic)
reactions and coagulation (bleeding) events. Merck submitted this requested
data within the NDA resubmission, which the FDA has now deemed complete for
review.

“We are pleased the FDA has accepted our resubmission of sugammadex sodium
injection for review, as this was a key milestone in our effort to bring this
medicine to the U.S.,” said Darryle D. Schoepp, Ph.D., senior vice president
and head of Neuroscience and Ophthalmology, Merck Research Laboratories.
“Sugammadex sodium injection is an example of Merck’s ongoing commitment to
developing new medicines for patients in hospital-based settings.”

Indication for ZEMURON^® (rocuronium bromide) Injection

ZEMURON Injection, from Merck, is indicated for inpatients and outpatients as
an adjunct to general anesthesia to facilitate both rapid sequence and routine
tracheal intubation, and to provide skeletal muscle relaxation during surgery
or mechanical ventilation.

Important safety information about ZEMURON

ZEMURON is contraindicated in patients known to have hypersensitivity (e.g.,
anaphylaxis) to rocuronium bromide or other neuromuscular blocking agents.

ZEMURON should be administered in carefully adjusted dosages by or under the
supervision of experienced clinicians who are familiar with the drug’s actions
and the possible complications of its use. The drug should not be administered
unless facilities for intubation, mechanical ventilation, oxygen therapy, and
an antagonist are immediately available. It is recommended that clinicians
administering neuromuscular blocking agents, such as ZEMURON, employ a
peripheral nerve stimulator to monitor drug effect, need for additional doses,
adequacy of spontaneous recovery or antagonism, and to decrease the
complications of overdosage if additional doses are administered.

Severe anaphylactic reactions to neuromuscular blocking agents, including
ZEMURON, have been reported. These reactions have, in some cases (including
cases with ZEMURON), been life threatening and fatal. Due to the potential
severity of these reactions, the necessary precautions, such as the immediate
availability of appropriate emergency treatment, should be taken. Precautions
should also be taken in those patients who have had previous anaphylactic
reactions to other neuromuscular blocking agents, since cross-reactivity
between neuromuscular blocking agents, both depolarizing and non-depolarizing,
has been reported.

ZEMURON has no known effect on consciousness, pain threshold, or cerebration.
Therefore, its administration must be accompanied by adequate anesthesia or
sedation.

In order to prevent complications resulting from residual paralysis, it is
recommended to extubate only after the patient has recovered sufficiently from
neuromuscular block. Other factors, which could cause residual paralysis after
extubation in the post-operative phase, (such as drug interactions or patient
condition) should also be considered. If not used as part of standard clinical
practice, the use of a reversal agent should be considered, especially in
those cases where residual paralysis is more likely to occur.

ZEMURON has not been studied for long-term use in the intensive care unit
(ICU). As with other non-depolarizing neuromuscular blocking drugs, apparent
tolerance to ZEMURON may develop during chronic administration in the ICU.
While the mechanism for development of this resistance is not known, receptor
up-regulation may be a contributing factor. It is strongly recommended that
neuromuscular transmission be monitored continuously during administration and
recovery with the help of a nerve stimulator. Additional doses of ZEMURON
(rocuronium bromide) or any other neuromuscular blocking agent should not be
given until there is a definite response (one twitch of the train-of-four) to
nerve stimulation. Prolonged paralysis and/or skeletal muscle weakness may be
noted during initial attempts to wean from the ventilator patients who have
chronically received neuromuscular blocking drugs in the ICU.

Myopathy after long-term administration of other non-depolarizing
neuromuscular blocking agents in the ICU alone or in combination with
corticosteroid therapy has been reported. Therefore, for patients receiving
both neuromuscular blocking agents and corticosteroids, the period of use of
the neuromuscular blocking agent should be limited as much as possible and
only used in the setting where in the opinion of the prescribing agent, the
specific advantages outweigh the risk.

ZEMURON has not been studied in malignant hyperthermia-susceptible patients.
Because ZEMURON is always used with other agents, and the occurrence of
malignant hyperthermia during anesthesia is possible even in the absence of
known triggering agents, clinicians should be familiar with early signs,
confirmatory diagnosis and treatment of malignant hyperthermia prior to the
start of any anesthetic.

Conditions associated with an increased circulatory delayed time, e.g.,
cardiovascular disease or advanced age, may be associated with a delay in
onset time.

The overall analysis of ECG data in pediatric patients indicates that the
concomitant use of ZEMURON with general anesthetic agents can prolong the QTc
interval.

Non-depolarizing neuromuscular blocking agents have been found to exhibit
profound neuromuscular blocking effects in cachectic or debilitated patients,
patients with neuromuscular diseases and patients with carcinomatosis. Certain
inhalation anesthetics, particularly enflurane and isoflurane, antibiotics,
magnesium salts, lithium, local anesthetics, procainamide and quinidine, have
been shown to increase the duration of neuromuscular block and decrease
infusion requirements of neuromuscular blocking agents. In these or other
patients in whom potentiation of neuromuscular block or difficulty with
reversal may be anticipated, a decrease from the recommended initial dose of
ZEMURON should be considered.

Resistance to non-depolarizing agents, consistent with up-regulation of
skeletal muscle acetylcholine receptors, is associated with burns, disuse
atrophy, denervation, and direct muscle trauma. Receptor up-regulation may
also contribute to the resistance to non-depolarizing muscle relaxants, which
sometimes develops in patients with cerebral palsy, patients chronically
receiving anticonvulsant agents, such as carbamazepine or phenytoin, or with
chronic exposure to non-depolarizing agents. When ZEMURON (rocuronium bromide)
is administered to these patients, shorter durations of neuromuscular block
may occur, and infusion rates may be higher due to the development of
resistance to non-depolarizing muscular relaxants.

Severe acid-base and/or electrolyte abnormalities may potentiate or cause
resistance to the neuromuscular blocking action of ZEMURON. No data are
available in such patients, and no dosing recommendations can be made.

ZEMURON, which has an acid pH, should not be mixed with alkaline solutions
(e.g. barbiturate solutions) in the same syringe or administered
simultaneously during intravenous infusion through the same needle.

ZEMURON may be associated with increased pulmonary vascular resistance, so
caution is appropriate in patients with pulmonary hypertension or valvular
heart disease.

In patients with myasthenia gravis or myasthenic (Eaton-Lambert) syndrome,
small doses of non-depolarizing neuromuscular blocking agents may have
profound effects. In such patients, a peripheral nerve stimulator and use of a
small test dose may be of value in monitoring the response to administration
of muscle relaxants.

If extravasation occurs, it may be associated with signs or symptoms of local
irritation. The injection or infusion should be terminated immediately and
restarted in another vein.

In clinical trials, the most common adverse reactions (2 percent) are
transient hypotension and hypertension.

There are no controlled studies documenting the use of ZEMURON before or after
other non-depolarizing muscle relaxants. Interactions have been observed when
other non-depolarizing muscle relaxants have been administered in succession.

The use of ZEMURON before succinylcholine, for the purpose of attenuating some
of the side effects of succinylcholine, has not been studied.

Please see U.S. prescribing information at:
http://www.merck.com/product/usa/pi_circulars/z/zemuron/zemuron_pi.pdf.

Merck's Commitment to Hospital-Based Medicine

Merck is committed to scientific excellence, and the discovery and development
of innovative treatments for patient care in hospitals. We strive to develop
new solutions to help our hospital-based customers deliver quality care to
their patients.

About Merck

Today's Merck is a global healthcare 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 consumer care 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 healthcare through far-reaching policies,
programs and partnerships. For more information, visit www.merck.com and
connect with us on Twitter, Facebook and YouTube.

Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of
the safe harbor provisions of the United States Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs and
expectations of Merck’s management and are subject to significant risks and
uncertainties. There can be no guarantees with respect to pipeline candidates
that the candidates will receive the necessary regulatory approvals or that
they will 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; Merck’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 Merck’s
patents and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

Merck 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 Merck’s 2011
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 ZEMURON (rocuronium bromide) at
http://www.merck.com/product/usa/pi_circulars/z/zemuron/zemuron_pi.pdf.

Contact:

Merck
Media Contacts:
Pam Eisele, 908-423-5042
Lainie Keller, 908-423-4187
or
Investor Contact:
Carol Ferguson, 908-423-4465
Justin Holko, 908-423-5088
 
Press spacebar to pause and continue. Press esc to stop.