Narcolepsy type 1 is a neurological disorder caused by a severe loss or absence of brain orexin neuropeptides. Orexins play a crucial role in regulating wakefulness and sleep cycles, and their deficiency leads to excessive daytime sleepiness and other symptoms associated with narcolepsy. According to the New England Journal of Medicine, to address this condition, researchers conducted a phase 2 clinical trial to test the efficacy of TAK-994, an oral medication that specifically targets the orexin receptor 2.
The trial was randomized, meaning patients were assigned randomly to receive either TAK-994 at different doses (30 mg, 90 mg, or 180 mg) or a placebo. The primary objective was to measure the average sleep latency on the Maintenance of Wakefulness Test (MWT) after 8 weeks of treatment, which assesses how long it takes for a person to fall asleep during specific times.
Out of the 73 participants, 41 patients’ data were available for analysis due to the early termination of the trial because of hepatic (liver-related) adverse events. The results showed promising improvements in sleepiness and cataplexy (sudden loss of muscle tone) in patients treated with TAK-994 compared to the placebo group. The higher the dose of TAK-994, the greater the improvements in sleep latency and reduction in daytime sleepiness.
Specifically, patients on the 180-mg dose experienced an average increase of 35 minutes in their ability to stay awake, while the placebo group showed a decrease of 2.5 minutes. Additionally, the Epworth Sleepiness Scale (ESS) score, which measures daytime sleepiness, decreased significantly in the TAK-994 groups compared to the placebo group. However, the trial was halted early due to some adverse events, primarily related to the liver.
Five patients experienced clinically significant elevations in liver enzyme levels, and three patients developed drug-induced liver injury. These findings are concerning and raise potential safety issues associated with TAK-994 use. Patients on TAK-994 also reported experiencing adverse events, with the most common being urinary urgency or frequency. While the medication showed promising effects on narcolepsy symptoms, the risk of hepatotoxicity (liver damage) needs to be carefully considered.
In conclusion, the phase 2 trial of TAK-994 for narcolepsy type 1 showed positive results in improving sleepiness and cataplexy compared to a placebo. However, the study was terminated early due to hepatic adverse events, indicating potential safety concerns. As further research and development progress, it will be essential to balance the benefits of the medication in managing narcolepsy symptoms with its associated risks. Patients with narcolepsy and healthcare providers should be aware of these findings and carefully consider treatment options based on individual patient needs and health conditions.
