Eisai Co. Ltd. and Purdue Pharma LP, partners in the development and commercialization of a dual orexin receptor antagonist for insomnia, said the drug improved subjective measures of both sleep onset and maintenance at the end of the six-month, placebo-controlled treatment period of a large phase III study. The data were incorporated into the pair's December FDA new drug application for lemborexant, which Eisai said could potentially reduce the risk of nighttime falls.

In corporate presentations, Eisai has framed the drug as part of a "holistic approach" to dementia that aims to prevent and slow disease progression while improving functional recovery for patients in various stages of Alzheimer's disease. While one part of that strategy attacks amyloid and tau, another including lemborexant targets the transformation of symptoms over time, with candidates like the synaptic functional modulator E-2730 and the next-generation AMPA receptor antagonist E-2082.

John Renger, head of research & development and regulatory affairs at Stamford, Conn.-based Purdue, told BioWorld lemborexant is "a keystone in establishing our future business," which will include neuroscience, oncology and non-opioid pain assets. Considering a recent Consumer Reports survey that found that more than one in 10 Americans who used a prescription drug for sleep took an opioid for that purpose, lemborexant could also offer an obvious opportunity to supplant that practice.

The possibility of regulating sleep and wakefulness via orexin, a neurotransmitter, has drawn significant interest from drugmakers because of its potential to help promote sleep while leaving patients capable of being awakened by external stimuli. It has already led to one already-marketed product for insomnia, Merck & Co. Inc.'s Belsomra (suvorexant), and on Monday was the subject of a €40 million (US$45.8 million) spinout by Heptares, a unit of Sosei Group Corp. (See story this issue.)

One key driver of continued interest is likely that, according to Eisai, population studies have shown that sleep disorders affect many more people worldwide than previously thought. Insomnia is the most common sleep disorder, affecting about 30 percent of the adult population worldwide, the company said.

Results from the lemborexant clinical development program to date are particularly relevant to older patients for whom the ability to awaken unimpaired remains an ongoing issue, Lynn Kramer, chief clinical officer and chief medical officer for Eisai’s neurology unit, told BioWorld.

Sunrise-2 data

Purdue and Eisai have worked together on lemborexant ever since 2015, when they first agreed to collaborate on the Eisai-originated drug. Sunrise 2 is the second phase III trial of the drug following Sunrise 1, a study that compared two doses of the drug to placebo as well as to an extended-release formulation of the Sanofi SA drug Ambien (zolpidem).

Sunrise 2 was a global 12-month randomized, controlled and double-blinded parallel-group study. It tested lemborexant's efficacy and safety in 949 adults, ages 18 to 88 years, with insomnia, which was characterized by difficulty falling asleep and/or staying asleep. During the first six months of the study, patients were randomized to receive either a 5-mg or 10-mg dose of lemborexant, or a placebo. The primary and key secondary efficacy objectives were assessed by patient self-reports via electronic sleep diaries.

At the end of the six-month placebo-controlled treatment period, investigators found median reductions from baseline in subjective sleep onset latency (sSOL), the study's primary efficacy endpoint, of about 22 minutes with lemborexant 5 mg and about 28 minutes with the 10-mg dose. The median reduction in sSOL from baseline for patients who received placebo was 11.43 minutes (p<0.0001 for all treatment groups).

Investigators also found improvements from baseline in subjective sleep efficiency with lemborexant vs. placebo and in the amount of time that patients taking the drug slept before waking up.

Serious adverse events (AEs) were reported in 2.2 percent of patients taking 5 mg of lemborexant and 2.9 percent taking the 10-mg dose vs. 1.6 percent of those taking placebo. But only one of the events was considered treatment-related. The most common AEs reported were somnolence, headache and influenza. Discontinuation rates due to AEs were comparable between placebo and lemborexant 5 mg (about 4 percent for each) and higher for lemborexant 10 mg (8.3 percent).

Six-month data from the study were presented at the Sleep Research Society's Advances in Sleep and Circadian Science conference in Clearwater Beach, Fla. Twelve-month data will be presented at a future scientific forum, Purdue said.

Earlier studies of lemborexant have supported other possible benefits of the drug, with one phase I trial finding a statistically significant difference in postural stability with both doses of lemborexant vs. extended-release zolpidem in the middle of the night and another finding no statistically significant impairment of driving performance after either single or multiple doses of lemborexant vs. placebo.

Tokyo-based Eisai said Monday that next steps for lemborexant will include submissions of regulatory filings on its home turf in Japan and in other regions and the initiation of a local phase III study of lemborexant in China.