Exploring Orexin Manipulation as a Possible Advancement in Narcolepsy Remedies
In the ongoing quest for effective treatments for narcolepsy, several promising candidates are making significant strides. Two of these, Alkermes' alixorexton and Takeda's oveporexton, are leading the way.
Alkermes' alixorexton, previously known as ALKS 2680, recently completed successful Phase 2 trials and is ready to enter Phase 3. The company announced in July 2025 that alixorexton demonstrated clinically meaningful and statistically significant improvements in wakefulness in patients with narcolepsy type 1 during the Vibrance-1 trial. The drug was well-tolerated and met the primary endpoint across all tested doses. Based on these results, Alkermes plans to rapidly initiate a global Phase 3 program for alixorexton in narcolepsy types 1 and 2, as well as idiopathic hypersomnia.
On the other hand, Takeda's orexin receptor agonist, oveporexton, has already completed two late-stage (Phase 3) trials successfully as of mid-2025. The positive Phase 3 results mark oveporexton as the treatment closest to regulatory approval among these new narcolepsy treatments. This advancement suggests Takeda may soon file for regulatory approval, though exact submission or FDA review dates are not yet detailed.
Centessa's ORX750, another OX2R agonist, is also being assessed for narcolepsy 1 and 2 and idiopathic hypersomnia. In Phase 1 data presented at the American Academy of Neurology Annual Meeting in California in April, ORX750 showed sustained effects in the 5 mg dose cohort throughout the eight-hour period post-dosing.
Axsome is also reviving the controversial drug reboxetine to treat narcolepsy. In Phase 3 trials, reboxetine significantly reduced the frequency of cataplexy attacks compared to placebo.
Narcolepsy is a neurological disorder that affects the regulation of sleep-wake cycles. Patients with narcolepsy can experience muscle weakness or dream activity of REM sleep while awake. The improvements measured with oveporexton included wakefulness, excessive daytime sleepiness, cataplexy, the ability to maintain attention, overall quality of life, and daily life functions.
In the trials, 72% of the patients achieved at least a 50% improvement in cataplexy after a month, with an 82% reduction at six months. Some patients who switched to placebo after being given AXS-12 experienced the worsening of cataplexy, compared to those who continued with AXS-12, whose cataplexy attacks decreased.
The National Institute of Neurological Disorders and Stroke has reported that people with narcolepsy experience less distinct boundaries between wakefulness and sleep. People with narcolepsy are more likely to enter REM sleep quickly, often within 15 minutes of falling asleep.
As these treatments move closer to approval, they offer hope for those living with narcolepsy and the debilitating symptoms it can cause.
- The biotech sector is contributing significantly to healthcare through the development of pharmaceuticals, with Alkermes' alixorexton, a promising candidate for narcolepsy treatment, preparing to enter Phase 3 trials based on its successful Phase 2 results.
- Science and medical-conditions intersect in the ongoing pursuit of effective narcolepsy treatments, as companies like Takeda advance their drugs, such as oveporexton, which has completed Phase 3 trials and shows promise as the treatment closest to regulatory approval.
- In the realm of health-and-wellness, various pharmaceutical companies are engaged in research on narcolepsy treatments, with Axsome working on the revival of reboxetine, a drug that has demonstrated efficacy in reducing cataplexy attacks in Phase 3 trials.
