Exploring orexin manipulation: a promising direction for narcolepsy therapies
In the ongoing quest to find effective treatments for narcolepsy, several pharmaceutical companies are making strides in developing new drugs that target the orexin system. This system plays a crucial role in regulating wakefulness and sleep.
Avadel Pharmaceutical's Lumryz, a sodium oxybate-based drug, had a challenging journey to regulatory approval but was finally greenlit in 2023 to treat cataplexy in patients with narcolepsy. Interestingly, Avadel also won an exclusivity battle against Jazz, the maker of Xyrem, in a U.S. court.
Takeda's oveporexton, another orexin receptor agonist, has shown promising results. In two phase 3 randomized, double-blind studies, oveporexton achieved statistically significant improvement compared to placebo in wakefulness, excessive daytime sleepiness, cataplexy, ability to maintain attention, overall quality of life, and daily life functions. The drug has received Breakthrough Therapy designation for the treatment of excessive daytime sleepiness in narcolepsy type 1 from the U.S. Food and Drug Administration (FDA) and the Center for Drug Evaluation of China's National Medical Products Administration. However, the clinical trial phases and regulatory approvals for oveporexton remain unspecified in the available information.
Centessa's ORX750, an OX2R agonist, is being assessed for narcolepsy 1 and 2, as well as idiopathic hypersomnia. ORX750 has shown sustained effects in phase 1 data, and its phase 2 results are expected to be presented this year. Like Takeda's oveporexton, the clinical trial phases and regulatory approvals for ORX750 are yet to be specified.
Axsome is reviving the controversial drug reboxetine to treat narcolepsy. In phase 3 trials, AXS-12 significantly reduced the frequency of cataplexy attacks compared to placebo. The clinical trial phases and regulatory approvals for AXS-12 are also unspecified in the available information.
These new orexin-targeting drugs, including Takeda's oveporexton, Centessa's ORX750, and Axsome's AXS-12, are promising new treatments for narcolepsy. Unlike traditional treatments that primarily target the hallmark symptoms, these drugs aim to address the root cause of narcolepsy, which involves less distinct boundaries between wakefulness and sleep, leading to quicker entry into REM sleep.
Alkermes' alixorexton, on the other hand, is making more progress. The drug has recently completed a positive Phase 2 trial in narcolepsy type 1 and is poised to begin global Phase 3 trials based on these results. Alixorexton demonstrated clinically meaningful wakefulness improvements and good tolerability.
Patients with narcolepsy can experience muscle weakness or dream activity of REM sleep while awake, making the development of these new treatments crucial for improving their quality of life. As research continues, we can look forward to more advancements in the treatment of narcolepsy.
[1] [Source for Alixorexton's Phase 2 results and upcoming Phase 3 trials] [2] [Source for the lack of detailed progress updates on Takeda's oveporexton, Centessa's ORX750, and Axsome's AXS-12] [3] [Source for Alixorexton's clinically meaningful wakefulness improvements and good tolerability] [4] [Source for the National Institute of Neurological Disorders and Stroke's report on the quicker entry into REM sleep in people with narcolepsy]
- The healthcare sector, particularly pharmaceuticals and biotech companies, are prioritizing the development of new treatments for narcolepsy, with drugs like Alixorexton from Alkermes and Takeda's oveporexton surfacing as promising options, aiming to address the root cause of the condition and improve the health-and-wellness of patients.
- Science continues to shed light on the complexities of narcolepsy, with researchers discovering that certain treatments, such as Alixorexton and drugs in development like ORX750 from Centessa and AXS-12 from Axsome, may help patients manage the less distinct boundaries between wakefulness and sleep, potentially leading to mental-health benefits.
- In the realm of sleep disorders, the ongoing research and advancements in the biotech industry, as exemplified by Alixorexton and other orexin-targeting drugs, offer hope for individuals suffering from narcolepsy, as they may eventually help improve their quality of life by addressing the specific symptoms associated with the condition.
