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

Update: Belsomra (suvorexant) Now FDA Approved - August 13, 2014

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

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Sep 10, 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).

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. Such statements may include, but are not limited to, statements about the benefits of the merger between Merck and Schering-Plough, including future financial and operating results, the combined company's plans, objectives, expectations and intentions and other statements that are not historical facts. Such statements are based upon the current beliefs and expectations of Merck's management and are subject to significant risks and uncertainties. Actual results may differ from those set forth in the forward-looking statements.

The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that all of the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; Merck's ability to accurately predict future market conditions; dependence on the effectiveness of Merck's patents and other protections for innovative products; and the exposure to 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).

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Posted: September 2012

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