Takeda is on track to submit its much-hyped narcolepsy drug to regulators this fiscal year after the orexin receptor 2 (OX2R)-selective agonist scored a pair of phase 3 wins.
The Japanese pharma had been assessing the drug, called oveporexton, in the FirstLight and RadiantLight trials in more than 270 patients across 19 countries. The studies hit their primary endpoints of demonstrating statistically significant improvements in excessive daytime sleepiness (EDS) as measured by the Maintenance of Wakefulness Test (MWT) across all doses of oveporexton tested when compared to placebo at week 12.
As with this key goal, secondary endpoints such as a different measure of EDS, ability to maintain attention, overall quality of life and weekly rate of cataplexy—a short episode of muscle weakness—were also achieved with p-values of less than 0.001.
No serious treatment-related adverse events were reported, noted Takeda. The most common adverse events were insomnia, urinary urgency and frequency.
The company hailed the results as validating oveporexton’s mechanism of action for the first time. The pharma is saving the detailed study data for a future medical meeting but already confirmed plans to submit an approval application to the FDA this fiscal year—which runs until March 2026.
The pharma believes the secret to oveporexton’s success is its ability to mimic the body’s natural orexin cycle. Orexin is a neuropeptide lacking in patients with narcolepsy that helps regulate waking, wakefulness, appetite and energy.
“Oveporexton is a testament to Takeda’s strength in discovering and developing a potential new class of medicines for difficult-to-treat diseases such as narcolepsy type 1,” Takeda CEO Christophe Weber said in the July 14 release. “Our leadership in orexin biology and building a multi-asset orexin franchise with transformative potential will position Takeda for long-term future growth.”
Takea has a lot riding on oveporexton, with the company eyeing between $2 billion and $3 billion in peak sales should the drug make it to market. Weber has previously pointed out that there are about 100,000 patients living with narcolepsy type 1 in the U.S alone, but the challenge is that many of these individuals remain undiagnosed or misdiagnosed.
“The treatment rate is about 75%, so we think that if you bring a very innovative medicine like oveporexton, you can really change the diagnosis level and really help these patients who don’t have a very good solution right now to treat narcolepsy,” the CEO told investors at the JP Morgan conference in January.
The drug is one of a clutch of six pipeline candidates that Takeda hopes will collectively generate peak sales between $10 billion and $20 billion should they all win approval.
“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,” Takeda’s head of R&D Andy Plump, M.D., Ph.D., said in this morning’s release.
“The positive results also reinforce the continued momentum for our late-stage pipeline, which we believe will deliver value to the patients we serve around the world,” Plump added.
Takeda has been exploring whether to wed the medication with a digital companion for monitoring patients' sleep. The company is also looking into artificial-intelligence-based algorithms to diagnose narcolepsy type 1 faster.
The pharma has other orexin agonists in the works, such as TAK-360 for narcolepsy type 2 and idiopathic hypersomnia.