Future Narcolepsy Therapies Focusing on Orexin Signaling
In the ongoing quest to find effective treatments for narcolepsy, several pharmaceutical companies are making significant strides. Among them, Alkermes' alixorexton (formerly ALKS 2680) is making headway, with the drug advancing through late-stage clinical development.
Alkermes' alixorexton has demonstrated positive, statistically significant Phase 2 results in improving wakefulness and related symptoms. The drug has shown good safety and tolerability, which supports a planned Phase 3 global trial in narcolepsy type 1 (NT1) that Alkermes aims to initiate soon. Extension studies and trials in narcolepsy type 2 (NT2) and idiopathic hypersomnia are also ongoing.
In contrast, Takeda's oveporexton, another OX2R agonist, lacks publicly available recent clinical trial progress or regulatory details as of mid-2025. Although mentioned as a promising orexin 2 receptor agonist, specific recent clinical trial updates or regulatory milestones for oveporexton have not been reported.
Takeda, however, has submitted a New Drug Application with the FDA for oveporexton, positioning it next in line in the narcolepsy treatment market.
Avadel Pharmaceutical's Lumryz, also made of sodium oxybate, faced setbacks due to patent issues but was given the green light in 2023 to treat cataplexy in patients with narcolepsy.
The OX2R agonist oveporexton has received Breakthrough Therapy designation for the treatment of excessive daytime sleepiness in NT1 from the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation of China's National Medical Products Administration.
Centessa's ORX750, another OX2R agonist, is being assessed for NT1 and NT2, as well as idiopathic hypersomnia. In phase 1 data, sustained effects were observed in the 5 mg dose cohort throughout the eight-hour period post dosing.
Patients with narcolepsy can experience muscle weakness or dream activity of REM sleep while awake. They often have less distinct boundaries between wakefulness and sleep, allowing them to enter REM sleep quicker, often within 15 minutes of falling asleep, according to the National Institute of Neurological Disorders and Stroke.
Jazz Pharmaceuticals, a company previously involved in the treatment of narcolepsy, has been caught up in an antitrust case for its FDA-approved narcolepsy drug, Xyrem, and is now paying $145 million as part of a settlement.
As these developments unfold, the race to find effective treatments for narcolepsy continues, with Alkermes' alixorexton currently leading the way towards regulatory approval.
- Alkermes' alixorexton, a pharmaceutical developed for the treatment of narcolepsy, has demonstrated positive Phase 2 results and is planned for a Phase 3 global trial in Narcolepsy Type 1 (NT1).
- The healthcare industry has seen various biotech companies, such as Takeda and Centessa, working on OX2R agonists like oveporexton and ORX750, aiming to treat neurological disorders like narcolepsy and its related conditions.
- In the realm of health-and-wellness, patents have played a significant role in the development of narcolepsy treatments, as evidenced by Avadel Pharmaceutical's Lumryz, which faced setbacks due to patent issues but was eventually approved to treat cataplexy in narcolepsy patients.
