Merck Announces New Phase III Data for Suvorexant, an Investigational Insomnia Medicine


September 10, 2012 7:30 am ET

Merck remains on target to file a New Drug Application with the FDA in 2012

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced new data for suvorexant, the investigational medicine
Merck is developing for the treatment of insomnia. The new data are from
one of the longest, continuously-dosed, placebo-controlled trials of a
sleep medication ever conducted. This 12-month study was designed to
assess the safety of suvorexant, while also evaluating its longer term
efficacy. Merck presented new results from a two-month discontinuation
phase that followed the 12-month study at the 21st Congress
of the European Sleep Research Society (ESRS).

“The methods used in this study allowed us to understand what happened
when patients who had been taking suvorexant every night for a year were
immediately switched to placebo, because what happens when patients stop
taking a sleep medication is a key concern for both patients and
healthcare professionals,” said James K. Walsh, Ph.D., executive
director and senior scientist, Sleep Medicine and Research Center, St.
Luke’s Hospital, and visiting professor, Department of Psychiatry,
Stanford University School of Medicine. “We found that the patients who
had been taking suvorexant for 12 months and were switched to placebo
saw their insomnia return, but clinically meaningful withdrawal symptoms
and rebound insomnia did not emerge. We also obtained efficacy data from
patients who continued to take suvorexant through 14 months.”

Specifically, results from the two-month discontinuation phase showed
that, after daily use of a consistent dose of suvorexant for one year,
patients who stopped taking the medicine experienced a return of their
sleeping difficulties to levels similar to those reported by patients
who received placebo over the course of the trial. Patients who
continued to receive suvorexant for the additional two months
experienced mean improvements in their ability to fall asleep and stay
asleep that were consistent with those seen over the first 12 months
compared to placebo. Adverse experiences reported in the two-month
discontinuation phase were generally consistent with those reported
during the 12-month study.

Merck researchers developed suvorexant to target and block orexins,
chemical messengers that originate from the hypothalamus (an important
sleep center in the brain) and help keep you awake. By blocking the
actions of orexins, suvorexant helps facilitate sleep. Merck plans to
file a New Drug Application (NDA) for suvorexant with the U.S. Food and
Drug Administration (FDA) in 2012. If approved, suvorexant would be the
first in a new class of medicines, called orexin receptor antagonists,
for use in patients with difficulty falling or staying asleep. Merck
anticipates that suvorexant will be evaluated by the Controlled
Substance Staff of the FDA.

“Suvorexant represents a new and different approach to treating
insomnia, an area of significant unmet need,” said Darryle D. Schoepp,
Ph.D., senior vice president and head of Neuroscience and Ophthalmology
franchise, Merck Research Laboratories. “We are enthusiastic about the
results of this long-term study, which provide important insights into
suvorexant and the chronic nature of insomnia. Merck is continuing with
plans to seek approval for suvorexant in the U.S. and in other countries
around the world.”

Study evaluated safety and efficacy of suvorexant in 12-month study
and two-month discontinuation phase

In Merck’s long-term, double-blind, Phase III trial, 781 patients with
primary insomnia were randomized to receive a consistent dose of
suvorexant (40 mg per night in patients 18-64 years of age or 30 mg per
night in patients 65 years and older) (n=521) or placebo (n=258) over a
12-month treatment period. Patients who completed the entire 12-month
study (n=484) continued into a two-month, randomized,
placebo-controlled, parallel-group discontinuation phase to evaluate
both the effects of stopping suvorexant and switching to placebo
(n=166), as well as the efficacy of continued suvorexant treatment at
months 13 and 14 (n=156). Patients who took placebo during the initial
12-month study continued to take placebo (n=162).

There were no primary efficacy endpoints in the 12-month study, which
had the main objective to evaluate the safety and tolerability of
suvorexant for up to 12 months of treatment. Secondary efficacy
endpoints in the 12-month study included mean change from baseline for
suvorexant compared to placebo in patient-reported measures of time to
fall asleep and total sleep time during the first month of treatment.
Other efficacy endpoints measured at all other time points in the
12-month study and two-month discontinuation phase were exploratory,
including assessment of time to return of sleeping difficulties.

Safety and tolerability were assessed by adverse event (AE) reports,
laboratory values, electrocardiograms, physical exams, vital signs,
withdrawal symptoms as evaluated by the Tyrer Benzodiazepine Withdrawal
Questionnaire (a questionnaire used to record the symptoms patients
experience when they stop taking medication) and patient-reported
rebound insomnia (a worsening of sleep measures compared with
pre-treatment levels). The primary time period for safety analyses in
this study was the 12-month treatment phase. Safety endpoints in the
discontinuation phase were secondary, with focus on evaluation of
rebound and withdrawal effects.

Results showed effects of suvorexant from 12-month study and
two-month discontinuation phase

During the first month of the 12-month study, patients who took
suvorexant reported that they fell asleep significantly faster, stayed
asleep significantly longer and spent significantly less time awake
during the night compared to patients who received placebo (p<0.001).
Also during the 12-month study, the incidence of patients reporting one
or more AEs was 69.5 percent among those who took suvorexant versus 63.6
percent among those who took placebo. The most common AEs reported at a
rate of at least five percent in patients who took suvorexant, and
reported more frequently than in patients who took placebo, were
sleepiness (13.2 percent vs. 2.7 percent), inflammation of the nasal
passages (8.1 percent vs. 7.8 percent), fatigue (6.5 percent vs. 1.9
percent), upper respiratory tract infection (5.4 percent vs. 4.3
percent) and dry mouth (5.0 percent vs. 1.6 percent). Full results from
the 12-month treatment period were presented at SLEEP 2012.

During the two-month discontinuation phase (months 13 and 14), patients
who stopped taking suvorexant (after 12 months) and switched to placebo
(for months 13 and 14) reported worsening of their ability to fall
asleep and stay asleep compared to patients who continued taking
suvorexant. This return of sleeping difficulties was similar to levels
reported by patients who received placebo for the full 14 months.
Specifically, at the end of the two-month discontinuation phase (end of
month 14), patients who switched from suvorexant to placebo reported
that it took them 14.9 minutes longer to fall asleep and that they slept
21.6 minutes less compared to patients who continued taking suvorexant
(p<0.0001 for both measures).

Additionally, compared to patients who continued on placebo, those who
switched from suvorexant (after 12 months) to placebo (for months 13 and
14) had no clinically meaningful evidence of withdrawal or rebound
insomnia when they stopped taking suvorexant.

The incidence of patients reporting one or more AEs during Months 13 and
14 was similar in both groups: 22.4 percent for those who continued on
suvorexant and 22.9 percent for those who switched from suvorexant to
placebo. The specific AEs with the highest incidence were inflammation
of the nasal passages (3.2 percent for patients who continued taking
suvorexant vs. 1.2 percent for patients who switched to placebo) and
drug administration errors (2.6 percent for patients who continued
taking suvorexant vs. zero percent for patients who switched to placebo).

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Pam Eisele, 908-423-5042
Noreen Verbrugge, 908-423-6301
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