Drug developers worldwide have made exciting progress in treating narcolepsy by focusing on a key brain protein called orexin-2. This protein helps control important functions like wakefulness, appetite, and arousal, making it a valuable target for new medications. Johnson & Johnson, for example, is testing a drug called seltorexant to help people with depression-related insomnia by blocking orexin-2. However, most researchers are working on ways to boost orexin-2 to help narcolepsy patients stay awake longer. Takeda Pharmaceutical is leading this effort with its drug oveporexton, which recently showed strong results in late-stage clinical trials for Type 1 narcolepsy—the most common form of the condition. At a medical conference, Takeda shared detailed findings from these studies. Researchers tested whether oveporexton could keep participants awake longer than a placebo using the “Maintenance of Wakefulness Test,” where participants sit in a quiet, dark room, and scientists measure how long it takes them to fall asleep. Initially, most participants fell asleep within five minutes, but after 12 weeks, those taking 2 mg doses of oveporexton twice daily stayed awake for about 20 to 25 minutes—a significant improvement. Another key symptom of narcolepsy is sudden muscle weakness called cataplexy. Takeda reported that oveporexton reduced cataplexy episodes by over 80% in treated patients. Patients also experienced fewer days with cataplexy, going from zero to four or five days per week. “This is the first time any drug has shown such a strong effect,” said Sarah Sheikh, Takeda’s head of global development. Patients also reported better quality of life, and the drug was generally safe, with no serious side effects like liver problems or vision issues. The most common side effects were insomnia and frequent urination, but most were temporary. Takeda plans to seek approval for oveporexton by the end of March. Analysts believe the drug could dominate the market, with potential sales reaching $1 billion annually. While Takeda is ahead, other companies like Alkermes, Eisai, and Centessa Pharmaceuticals are also developing treatments. Alkermes presented promising results for its once-daily drug alixorexton, which helped patients stay awake longer and reduced sleepiness and cataplexy. Eisai also shared early-stage data for its drug E2086, showing it kept patients awake significantly longer than a placebo. Despite these advancements, stock prices for these companies varied, with Takeda’s stock slightly down, Eisai’s up, and Alkermes’ down. Currently, the FDA has approved a few orexin-blocking drugs for insomnia, including Belsomra, Quviviq, and Dayvigo. This new research offers hope for better narcolepsy treatments in the future.