Takeda's Oveporexton Phase 3 Trials Meet All Endpoints; Data Published In NEJM

(RTTNews) - Takeda (TAK) announced that Phase 3 data for oveporexton (ORZEYFUL) in adults with narcolepsy type 1 (NT1) have been published in the New England Journal of Medicine (NEJM).

The data from the global FirstLight and RadiantLight studies showed statistically significant improvements across key measures of NT1 compared with placebo.

Narcolepsy Type 1 (NT1)

Narcolepsy type 1 is a rare, chronic neurological disorder caused by loss of orexin-producing neurons. It is characterized by excessive daytime sleepiness and cataplexy, or sudden loss of muscle tone, and can also affect nighttime sleep, attention, and daily functioning.

Oveporexton

Oveporexton is an oral, selective orexin receptor 2 (OX2R) agonist designed to restore orexin signaling and address the underlying orexin deficiency associated with NT1.

The FDA approved oveporexton under the brand name ORZEYFUL in August 2026 for the treatment of NT1 in adults. It previously received Breakthrough Therapy designation from the FDA for excessive daytime sleepiness in NT1 and Sakigake designation in Japan.

FirstLight & RadiantLight Study

The Phase 3 program comprised two global, multicenter, randomized, placebo-controlled studies conducted across 19 countries.

FirstLight enrolled 168 participants, randomized to twice-daily 2 mg, 1 mg, or placebo, while RadiantLight enrolled 105 participants, randomized to twice-daily 2 mg or placebo. Both studies evaluated efficacy, safety, and tolerability over 12 weeks.

Efficacy & Safety Results

Both studies met their primary and secondary endpoints, with consistent, statistically significant improvements versus placebo in wakefulness, sleepiness, cataplexy, disease severity, and quality of life across doses at Week 12.

At Week 12, median weekly cataplexy rates fell by 79.0% to 88.8% with oveporexton, compared with 27.7% to 39.1% with placebo.

Oveporexton also improved all assessed domains of the Narcolepsy Severity Scale (NSS-CT), including excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis.

More than 70% of treated participants reported mild disease severity on the NSS-CT scale.

Nearly 97% of patients receiving oveporexton reported an improvement in overall narcolepsy symptoms on the Patient Global Impression of Change scale (PGI-C).

All oveporexton dose groups also reached normative thresholds for wakefulness and daytime sleepiness on the Maintenance of Wakefulness Test (MWT) and Epworth Sleepiness Scale (ESS), respectively.

Most participants reached or exceeded normal thresholds for quality-of-life measures assessed using the SF-36 survey and EuroQol-5 Dimensions 5-Levels (EQ-5D-5L).

Oveporexton was generally well tolerated, with a safety profile consistent with earlier clinical studies. The most commonly reported adverse events included insomnia, urinary urgency, and urinary frequency.

The NEJM publication follows the FDA's August 2026 approval of ORZEYFUL, making it the first approved orexin therapy for adults with NT1.

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