Eisai and Purdue Pharma have presented new clinical trial results of their dual orexin receptor antagonist lemborexant, which they think could become a new force in the sleep disorder market.
The SUNRISE 1 trial—which reported top-line data in March—plus two new phase 1 studies were presented at the SLEEP 2018 conference in Baltimore yesterday and, say the partners, reinforce their view that lemborexant can help improve sleep with no hangover effect on waking and no grogginess if patients have to get up in the night.
The phase 3 trial included a head-to-head assessment of lemborexant and an extended-release form of widely used sleep drug zolpidem, which is available generically, and found that Eisai and Purdue’s drug was more effective at keeping patients over the age of 55 asleep throughout the night, avoiding early awakening. The two new phase 1 trials looked at other variables that are important to getting a good night’s sleep.
Study 108 compared the effects of lemborexant, zolpidem and placebo given at bedtime on postural instability after patients were awoken in the night by exposure to noise. The main measure was body sway, and while lemborexant-treated patients overall weren’t as steady on their feet as those on placebo, they did significantly better than those on zolpidem.
With the widely used insomnia drug, body sway occurred at almost three times the level that would be seen if the subject had drunk enough alcohol to put them close to the legal driving limit. A lower dose of lemborexant (5 mg) caused no clinically meaningful increase in body sway, while a higher (10 mg) dose increased it “to just above the clinically meaningful threshold.”
The study also checked on the effects of the drugs the following morning and found no difference between Eisai and Purdue’s drug and placebo on postural instability, which Eisai Chief Medical Officer Lynn Kramer, M.D., notes is “the single best predictor of falls” in older people.
There was no significant difference between placebo and both study drugs in the noise threshold needed to wake subjects up, but those on lemborexant found it easier to fall asleep again thereafter.
The second trial, Study 106, investigated the tendency of lemborexant and another widely used generic sleep drug called zopiclone to impair driving ability in the morning after a bedtime dose. It tested the amount of weaving—or standard deviation of lateral position in scientific parlance—and found that lemborexant had no significant effect on performance, while zopiclone significantly increased SDLP compared to placebo.
No test drives were stopped on safety grounds before completion in the lemborexant group, while three in the zopiclone group were halted, although overall that accounted for less than 1% of all drives tested.
Eisai said earlier this year it intends to file for approval of lemborexant for insomnia later this year once the results of a second, confirmatory phase 3 trial come in.
It’s also got a phase 2 in play for lemborexant in patients with irregular sleep-wake rhythm disorder, and in mild to moderate Alzheimer's dementia, which is already underway.