Investigating Ulotaront for REM Suppression in Sleep Disorders

Ulotaront is a novel trace amine-associated receptor 1 and serotonin 5-HT1A receptor agonist being developed for the treatment of schizophrenia. Previous studies showed ulotaront suppressed rapid eye movement (REM) sleep in mice models and healthy volunteers. Researchers, led by Dr. Steven Szabo, explored the potential impact of ulotaront in patients with narcolepsy-cataplexy.

In their study, the authors concluded the effects of ulotaront on REM did not produce a statistically significant improvement in narcolepsy-cataplexy symptoms; however, they noted acute ulotaront treatment reduced nighttime REM time, and sustained ulotaront treatment reduced daytime sleep onset REM periods (SOREMPs). Their findings were presented in Sleep Medicine.

Ulotaront Treatment Lacks Effect in Narcolepsy-Cataplexy

The multicenter, phase 1b, randomized crossover study enrolled 16 patients with narcolepsy-cataplexy to receive oral ulotaront 25 mg or 50 mg daily for 2 weeks, or a matching placebo.

Compared with placebo, investigators found acute ulotaront treatment at both the 25-mg and 50-mg doses reduced total nighttime REM minutes, and sustained treatment for 2 weeks at either dose reduced the mean daytime SOREMPs number during multiple sleep latency tests.

Notably, while ulotaront decreased the overall mean number of cataplexy events from baseline during treatment, neither the 25-mg (P=.76) nor 50-mg (P=.82) doses were statistically significant compared with placebo. Notably, authors reported there were no significant improvements in patient or clinician measures of sleepiness after treatment in any group.

The disparity between the positive effects of ulotaront on REM sleep parameters and the lack of meaningful symptom improvement led the authors to theorize that “alternative neurobiological mechanisms may be responsible” for driving the symptoms of these patients.

“Changes in REM, in spite of large effect sizes observed with ulotaront therapy, are not predictive of efficacy in reduction of cataplexy in narcolepsy,” summarized Dr. Szabo and colleagues.

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