Takeda and Alkermes have presented data from their orexin receptor 2 (OX2R) drugs in narcolepsy type 1 (NT1); however, analysis predicts that Takeda’s drug will achieve higher sales due to a first-to-market advantage.
At the World Sleep Congress 2025, Takeda presented data from the 12-week Phase III FirstLight (NCT06470828) and RadiantLight (NCT06505031) trials, which showed that in the twice-daily 2mg cohorts, Maintenance of Wakefulness Test (MWT) scores were 21.8 and 24.6, respectively, putting patients in the normative range.
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The 1mg cohort from FirstLight achieved a score of 19.3 points, 0.7 points below the normative range.
Meanwhile, the placebo cohorts in FirstLight and RadiantLight achieved scores of 4.5 and 3.3 points, respectively, after 12 weeks.
On the Epworth Sleepiness Scale (ESS), patients treated with 2mg cohorts dropped from 19 points to 7 points and from 17.3 points to 6.4 points in FirstLight and RadiantLight. In the 1mg cohort, the ESS score dropped from 18.2 to 8.3 points.
Other endpoints achieved include a reduction in cataplexy and a reduction in the Narcolepsy Severity Scale for Clinical Trials (NSS-CT).
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By GlobalDataIn nighttime symptoms, 85% of patients treated with oveporexton were suffering no hallucinations or sleep paralysis after 12 weeks of treatment, and 67% showed meaningful improvement on disturbed nighttime sleep (DNS).
Takeda added that the drug was generally well-tolerated with a safety profile consistent across clinical studies to date. No serious treatment-related adverse events (AEs) were reported. The most common AEs were insomnia, urinary urgency and frequency.
Despite presenting seemingly overwhelmingly positive data, Takeda’s stock, listed on the New York Stock Exchange, only lifted slightly, from a $15.40 close on 5 September to a market open of $15.65 on 8 September.
Meanwhile, on the Tokyo Exchange, Takeda’s stock also rose slightly, from a 5 September close of Y4,574.00 ($30.99) to an 8 September open of Y4,612.00 ($31.24).
FirstLight study’s principal investigator Dr Emmanuel Mignot said: “Takeda’s groundbreaking efforts targeting the OX2R in clinical studies led to positive Phase III results for oveporexton, bringing us a major step closer to having the first orexin therapy that addresses the underlying cause of NT1, with the potential of transforming the current treatment paradigm.”
In the 8 September investor call, in which it shared the data presented earlier in the day at the conference, Takeda said it expects to file for approval of the OX2R in the US and other countries during fiscal year 2025, which, if approved, would make it the first drug of this class to be used in NT1. The company had previously announced that the trials had met their endpoints in July 2025.
Oveporexton (TAK-861) is a first-in-class investigational oral OX2R-selective agonist, targeting the cause of NT1. GlobalData predicts the drug will be approved in 2026, with a 2031 sales forecast of $1.26bn.
GlobalData is the parent company of Clinical Trials Arena.
Alkermes’ six-week data also strong
Alkermes has also reported data from a six-week trial of its OXR2-selective agonist alixorexton; however, the data comes from the Phase II Vibrance 1 study (NCT06358950), meaning the drug currently trails Takeda’s therapy in the development journey.
In the 4mg, 6mg and 8mg cohorts, the drug respectively showed a 22.2 point, 24.1 point and 26.0 point improvement on the MWT. On the ESS, in the low, medium and high dose cohorts, there were reductions of 6.4, 8.7, and 8.3 points, respectively.
On the key secondary endpoint evaluating mean weekly cataplexy rates, alixorexton demonstrated numerical and clinically meaningful improvements across all doses compared to placebo at weeks five and six and, on the pre-specified analysis, achieved statistical significance at the 6mg dose.
Statistically significant improvement in the NSS-CT, PROMIS-Fatigue and British Columbia Cognitive Complaints Inventory (BC-CCI) was also observed in the trial.
Alkermes CEO Richard Pops said: “These data represent a significant new contribution to the evidence base supporting the utility of OXR2 agonists in central disorders of hypersomnolence and support exploration of the broader therapeutic potential of the class across a range of psychiatric and neurological conditions. We believe orexin-targeted therapeutics represent a significant opportunity for growth.”
Based on these results, Alkermes plans to initiate a global Phase III programme for alixorexton in the first quarter of 2026.
GlobalData predicts a 2028 approval for Alkermes’ OX2R, with a sales forecast of $804m in 2031.
