Takeda announced this week that its candidate small molecule oral drug, oveporexton, for treating type I narcolepsy achieved good results in two key Phase III trials, which the big pharma hopes will lead to regulatory approval.
Type I narcolepsy is thought to affect around 126,000 people in the United States, but is likely underdiagnosed, so the actual number of people affected is probably higher. It is caused by a loss of neurons in the brain that produce a neuropeptide called orexin that helps to regulate wakefulness and REM sleep.
Symptoms of type I narcolepsy include excessive sleepiness during the day, disrupted sleep at night, and sudden loss of muscle tone (cataplexy). This condition can be diagnosed by measuring orexin levels in the cerebrospinal fluid. Current treatments only target the symptoms, for example, the use of stimulants to ward off daytime sleepiness, and do not target the direct cause.
In contrast, oveporexton selectively mimics the action of the orexin receptor 2 (OX2R), which stimulates increased production of orexin in people with the condition. Increasing levels of this neuropeptide, which is abnormally low in people with type I narcolepsy, acts to restore normal or nearly normal sleep patterns and reduce cataplexy in these individuals.
Overall, 273 individuals from 19 countries were enrolled in two placebo-controlled Phase III trials called FirstLight and RadiantLight. Low and high dose orexin was tested against placebo in the two trials, and the primary endpoint was an improvement in excessive daytime sleepiness, with secondary endpoints including other measures of sleep status and cataplexy, as well as factors like attention span and quality of life.
The two studies achieved both their primary and secondary endpoints, and oveporexton was well tolerated by participants with no major side effects reported. The most common minor adverse events were insomnia and increased urination and urgency of urination.
“Oveporexton is a testament to Takeda’s strength in discovering and developing a potential new class of medicines for difficult-to-treat diseases such as narcolepsy type I,” said Christophe Weber, president and CEO at Takeda, in a press statement.
“The comprehensive assessments from our Phase III studies build on the transformative results we saw with our Phase IIb study with most participants reaching normative ranges and reporting clinically meaningful improvement across a broad range of symptoms at the end of the 12-week treatment period,” added Andy Plump, MD, PhD, president of R&D at Takeda.
The pharma company now plans to submit an approval application to the FDA later this year based on the results of these trials. Takeda is also developing other targeted orexin agonists, such as TAK-360, which is being investigated for the treatment of narcolepsy type II and idiopathic hypersomnia.
