Oveporexton Improves Excessive Daytime Sleepiness in Narcolepsy Type 1

Topline data were announced from two phase 3 trials evaluating oveporexton in patients with narcolepsy type 1 (NT1).

NT1 is a rare neurological disorder caused by the loss of orexin-producing neurons in the brain, which regulate wakefulness and sleep. Symptoms of NT1 include excessive daytime sleepiness, cataplexy, disrupted nighttime sleep, sleep paralysis and hallucinations. 

Oveporexton, previously known as TAK-861, is an oral orexin receptor 2 (OX2R)-selective agonist. It is designed to promote wakefulness and reduce abnormal rapid eye movement (REM)-sleep-like phenomena, including cataplexy, in patients with NT1 by addressing the underlying orexin deficiency. 

The phase 3 trials FirstLight (ClinicalTrials.gov Identifier: NCT06470828) and RadiantLight (ClinicalTrials.gov Identifier: NCT06505031), evaluated the safety and efficacy of oveporexton for the treatment of narcolepsy with cataplexy (≥4 partial or complete episodes of cataplexy per week) in patients aged 16 to 70 years old. 

In FirstLight, study participants (N=168) were randomly assigned to receive high dose oveporexton, low dose oveporexton, or placebo for 12 weeks. In RadiantLight, study participants (N=105) were randomly assigned to receive either high dose oveporexton or placebo for 12 weeks. The primary endpoint for both studies was the change from baseline to week 12 in mean sleep latency as measured by the Maintenance of Wakefulness Test (MWT). 

Findings showed that at all doses, oveporexton  statistically significantly improved excessive daytime sleepiness (EDS) as measured by the MWT compared with placebo (P <.001). The studies also met key secondary endpoints demonstrating significant improvements in wakefulness, EDS, cataplexy rate, ability to maintain attention, quality of life, and daily life functions with oveporexton vs placebo.

The safety profile of oveporexton was comparable to that observed in a phase 2b study (ClinicalTrials.gov Identifier: NCT05687903). The most common adverse events reported were insomnia, urinary urgency and frequency. 

“The studies were accelerated at an unprecedented pace with the aim to bring this potential treatment to people living with narcolepsy type 1 as quickly as possible,” said Andy Plump, MD, PhD, president of R&D at Takeda. “The comprehensive assessments from our phase 3 studies build on the transformative results we saw with our phase 2b study with most participants reaching normative ranges and reporting clinically meaningful improvement across a broad range of symptoms at the end of the 12-week treatment period.” 

According to Takeda, the Company intends to submit a New Drug Application in 2025. Full results from the trial will be presented at upcoming medical congresses. 

This article originally appeared on MPR