Key takeaways:

• Oveporexton is the first FDA-approved medicine to treat narcolepsy type 1 holistically.
• Median cataplexy-free days improved from 0 days at baseline to 4 to 5 days per week compared with placebo.

The FDA has approved oveporexton for the treatment of narcolepsy type 1 in adults, according to officials with Takeda, the drug’s developer.

Oveporexton (Orzeyful, Takeda), an oral orexin receptor 2 agonist, is the first medicine indicated in the U.S. to treat narcolepsy type 1 (NT1) holistically instead of treating individual symptoms, Takeda officials said in a press release.

The oral orexin receptor 2 agonist directly targets the loss of orexin signaling.

“Until now, people have managed narcolepsy type 1 with treatments that target symptom relief,” Emmanuel Mignot, MD, PhD, Craig Reynolds Professor of Sleep Medicine at Stanford University, said in a statement.

“As the first and only approved orexin therapy to treat the broad spectrum of the disease, Orzeyful can enable a different kind of conversation in the doctor’s office about treatment options,” Mingot said.

NT1 is a chronic neurological disease characterized by a loss of orexin, a neuropeptide that helps regulate wakefulness and the transition between sleep and wake states. The consequences for the roughly 120,000 people in the U.S. with NT1 can include excessive daytime sleepiness, cataplexy, cognitive symptoms and disrupted nighttime sleep, according to the release.

Oveporexton, administered in a tablet form, works by directly targeting the loss of orexin signaling, FDA officials said in a separate press release.

In the global phase 3 FirstLight and RadiantLight clinical studies, adults taking Orzeyful experienced significant improvements across narcolepsy type 1 symptoms compared with placebo, according to the release.

In both trials, doses were administered twice daily for 12 weeks, including 1 mg doses in the FirstLight trial and 2 mg doses in the RadiantLight trial. The trials included 273 total participants (mean age, 31.1 years; 54.2% female) who were randomly assigned to a 1 mg/1 mg group (n = 61), a 2 mg/2 mg group (n = 136) or a placebo group (n = 76).

Mean sleep latency, measured using the Maintenance Wakefulness Test (MWT), was 4.8 minutes at baseline. The baseline score on the Epworth Sleepiness Scale (ESS) was 18.1 and the median weekly cataplexy rate (WCR) was 26 attacks.

At week 12, MWT mean sleep latency had a least-squares mean difference of 15.90 minutes versus placebo (95% CI, 12.65-19.15) for the 1mg/1mg group and 19.16 (95% CI, 16.65-21.68 for the 2 mg/2 mg group.

The least squares mean difference versus placebo for ESS was –8.27 seconds (95% CI, –9.82; –6.73) for the 1 mg/1 mg group and –9.71 (95% CI, –10.92; –8.5) for the 2 mg/2 mg group.

The incidence rate ratio for WCR versus placebo was 0.28 attacks (95%, 0.19-0.41) for the 1 mg/1 mg group and 0.32 attacks (95% CI, 0.23-0.45) for the 2 mg/2 mg group.

Overall, the majority of participants in the 2 mg/2 mg group achieved wakefulness within the normative range, according to the release. Median cataplexy-free days improved from 0 days at baseline to 4 to 5 days per week compared with placebo.

Takeda noted that oveporexton’s safety profile in these studies was consistent with prior research and that it was generally well tolerated. Insomnia, urinary urgency and frequency, and excessive saliva were the most common side effects.

Officials with Takeda said they are preparing to make Orzeyful available in the U.S. following the completion of the DEA scheduling process, with controlled substance classification expected within 90 days.

For more information:

Emmanuel Mignot, MD, PhD, can be reached at neurology@healio.com.