A Phase 2 clinical study found TAK-994 to be relatively effective in reducing symptoms like excessive daytime sleepiness (EDS) and cataplexy (sudden, uncontrollable muscle weakness often triggered by strong emotions). So then why has the therapy not continued forward in clinical studies for now?
According to reporting from Medical XPress, French researchers recently sought to understand whether TAK-994 could be an effective therapeutic option for people with narcolepsy type 1, or narcolepsy with cataplexy. TAK-994 is an orally administered orexin receptor 2 agonist. On a pathophysiologic level, narcolepsy is characterized by the loss of orexin producing brain neurons. So TAK-994 is designed to address this at the source.
In the Phase 2 study, 73 participants were split into four groups. One group received a placebo twice each day. The others received 30mg, 90mg, or 180mg twice each day. The study findings, published in the New England Journal of Medicine, explain that the primary endpoint was change from baseline in sleep latency, or how long it takes you to fall asleep, with secondary endpoints of sleepiness and weekly cataplexy episodes.
Primary data is available from 41 participants. This data highlights how TAK-994 reduced sleepiness and significantly improved sleep latency, particularly in those taking 180mg twice daily. Similarly, the drug proved to reduce cataplexy episodes as well.
But wait, you might be asking. Why is there only data from 41 participants when 73 people enrolled?
Well, the trial was actually terminated early due to adverse effects. The most common adverse effect was changes in urinary urgency or frequency. However, there were a number of elevated liver enzymes that suggested hepatoxicity.
Narcolepsy is a chronic neurological sleep disorder. This condition alters how the brain regulates sleep-wake cycles, leading to excessive daytime sleepiness that can be debilitating. EDS often makes it difficult to stay awake. People with narcolepsy may fall asleep suddenly and remain a sleep for seconds to minutes at a time – sometimes longer. This condition may also be characterized by hallucinations during sleep or when waking. Symptoms often appear between ages 10 to 30 and may also include:
- Sleep paralysis
- Anxiety and depression
- Difficulty focusing
- Obstructive sleep apnea
Sodium oxybate and gamma-hydroxybutyrate can be used to manage cataplexy. Not every person with narcolepsy also has cataplexy. For managing narcolepsy, Xyrem and pitolisant are both approved. However, continued research is needed to identify any potential cure that might exist.