Alkermes, Inc.

Takeda is aiming for $2 billion to $3 billion in peak revenue for oveporexton as a treatment for narcolepsy type 1.\n Takeda and Alkermes both took data from their orexin receptor 2 (OX2R)-selective agonists to Singapore this morning as the race to get a new class of narcolepsy drugs approved heats up.Takeda assessed its drug, called oveporexton, in the FirstLight and RadiantLight phase 3 trials in more than 270 patients across 19 countries. Takeda announced back in July that the studies hit their primary endpoints of demonstrating statistically significant improvements in excessive daytime sleepiness as measured by the Maintenance of Wakefulness Test (MWT) across all doses of oveporexton tested when compared to placebo at Week 12.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.Now, the pharma has pulled back the curtain on the data for the phase 3 wins. Specifically, the majority of patients who were treated with the twice-daily 2-mg dose of oveporexton achieved wakefulness within what is considered the “normative range” as measured by the MWT, Takeda explained in a presentation at the World Sleep 2025 Congress in Singapore this morning.In addition, “close to” 85% of patients receiving this dosing regimen achieved a score on a separate sleepiness scale that was “comparable to healthy individuals,” Takeda noted.Median days with patients not experiencing cataplexy—a sudden loss of muscle control that is a defining symptom of narcolepsy type 1 (NT1)—rose from zero days at baseline to 4-5 days a week by Week 12.While the mean narcolepsy severity score among patients in both the FirstLight and RadiantLight studies began at around 30-31, by Week 12, this had dropped to a score of around 10, according to Takeda’s presentation.“More than 70% of participants [are] reporting the lowest severity level across doses,” the company pointed out. A total of 97% of patients reported improvements on a self-rated symptoms scale, Takeda added.The most common treatment-emergent adverse events (TEAEs) were insomnia, along with urinary frequency and urgency. There were no serious TEAEs in the RadiantLight study, and neither of the two TEAEs in FirstLight was deemed related to oveporexton.With Takeda on track to begin approval filings to the FDA and international regulators this fiscal year, the company is aiming for $2 billion to $3 billion in peak revenue potential for oveporexton as a treatment for NT1.The company initially has its eye on the U.S., where it is hoping oveporexton will “unlock the potential of a new era of care in NT1.”“We are excited to share these transformative results at World Sleep, which demonstrate the potential for a new era of care defined by multiple treatment measures that matter to patients,” Sarah Sheikh, head of the neuroscience therapeutic area unit and global development at Takeda, said in a release. Alkermes following close behind Alkermes is behind Takeda, having posted a phase 2 win for its own contender, alixorexton, just days after Takeda’s disclosure in July. Not to be outdone at the World Sleep 2025 Congress, Ireland-headquartered Alkermes also shared the data behind its midstage success at the same event.While Takeda’s oveporexton needs to be taken twice a day, Alkermes hailed its detailed results as the “first OX2R agonist to demonstrate clinically meaningful and statistically significant impact on wakefulness, cognition and fatigue with once-daily dosing.”Specifically, all alixorexton dose groups achieved “normative wakefulness” on the MWT, with observed mean sleep latency of approximately 24 minutes, 26 minutes and 28 minutes for the 4-mg, 6-mg and 8-mg doses, respectively.All doses evaluated resulted in “numerical and clinically meaningful improvements” in weekly cataplexy rates, with more than 40% of patients in the 6-mg and 8-mg cohorts seeing cataplexy disappear completely by Week 6.The safety profile appeared similar to oveporexton, with no serious TEAEs reported, while the most common TEAEs were frequent urination, insomnia, salivary hypersecretion and blurred vision.Assessing this drug class earlier in the year, William Blair analysts said experts they had spoken to suggested that urinary and insomnia issues “may be viewed as worthwhile trade-offs to patients.” For Alkermes, that still leaves blurred vision as a potential barrier, but the company stressed in its release that this was “mostly mild and intermittent and largely occurred and resolved within the first three days of treatment.”Alkermes certainly isn’t losing any sleep over the side effect profile, instead reaffirming its desire to take alixorexton into phase 3 in the first quarter of 2026.“These data represent a significant new contribution to the evidence base supporting the utility of orexin 2 receptor 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,” Alkermes CEO Richard Pops said in a Sept. 8 release.Takeda may be in the lead, but close observers think there’s everything to play for. Back in March, Leerink analysts were pointing out that despite oveporexton’s “significant first-mover advantage,” the drug could still have a fight on its hands when compared to once-daily dosing options—of which Centessa Pharmaceuticals\' own OX2R agonist ORX750 is another player.Talking at a Goldman Sachs event in June, Pops said Takeda’s candidate is “proof of the pharmacology, but it’s an incomplete product.” Pops’ view reflected the fact Takeda’s molecule is given once in the morning and again a few hours later and is only on course to come to market in NT1.

Alkermes and Takeda on Monday presented positive study data for their respective orexin receptor 2 (OX2R) agonists at the World Sleep congress, with the Japanese drugmaker appearing to hold a slight edge in the race to bring the narcolepsy drugs to market. Takeda announced in July that a pair of Phase III studies of oveporexton (TAK-861) for patients with narcolepsy type 1 (NT1) met all of its primary and secondary endpoints, setting up marketing applications for the twice-daily oral therapy. The FirstLight trial enrolled 168 participants, while RadiantLight recruited 105 patients, with both utilising the Maintenance of Wakefulness Test (MWT) as the main goal. Results detailed at the World Sleep meeting showed that the majority of participants treated with the 2-mg dose of oveporexton achieved wakefulness within what is considered the "normative range" as measured on the MWT. In addition, nearly 85% of patients on this dose achieved Epworth Sleepiness Scale (ESS) scores at week 12 comparable to healthy individuals. Takeda added that the median number of days with participants not experiencing cataplexy versus placebo improved from zero days at baseline to 4-5 days per week at week 12. Further, oveporexton showed statistically significant changes from baseline in the narcolepsy severity scale (NSS-CT) total score compared to placebo with more than 70% of patients reporting the lowest severity level across doses, while 97% also saw improvements in narcolepsy symptoms as assessed by the self-rated Patient Global Impression of Change (PGI-C) scale. Emmanuel Mignot, principal investigator for the FirstLight trial, said the results for oveporexton bring "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." Focus on side effects Although Takeda is ahead of Alkermes in the race to bring an OX2R agonist to market, the side-effect profiles of the two drugs will also be key to their uptake, if they are ultimately approved. The Japanese pharma noted that the most common adverse events associated with oveporexton in the two Phase III studies were insomnia, urinary urgency and frequency, which were mainly mild to moderate. For its candidate alixorexton (ALKS 2680), Alkermes said that in the Phase II Vibrance-1 study, the once-daily drug was also associated with mild-to-moderate cases of insomnia and urinary urgency. However, in addition, alixorexton was linked to adverse events consisting of pollakiuria, salivary hypersecretion and blurred vision — the company noted that the latter was mostly mild and intermittent and largely occurred and resolved within the first three days of treatment. Meanwhile, Alkermes on Monday reaffirmed plans to push alixorexton into a Phase III programme in the first quarter of next year, having signalled its intent when Vibrance-1 was top-lined as positive in July. The mid-stage trial randomised 92 patients with NT1 to receive the drug at once-daily doses of 4 mg, 6 mg or 8 mg, or placebo for six weeks. Data presented at the World Sleep congress showed that all alixorexton dose groups achieved "normative" wakefulness on the MWT with observed mean sleep latency of approximately 24 minutes, 26 minutes and 28 minutes for the 4-mg, 6-mg and 8-mg arms, respectively. In addition, all doses demonstrated "numerical and clinically meaningful improvements" in weekly cataplexy rates compared to placebo, with more than 40% of those in the 6-mg and 8-mg groups achieving a 100% reduction in cataplexy during week six. "These data represent a significant new contribution to the evidence base supporting the utility of orexin 2 receptor 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," commented Alkermes CEO Richard Pops. For related analysis, read Spotlight On: Alkermes’ alixorexton retains spot in orexin race – and shot at crown and see, KOL Views Q&A: Takeda’s oveporexton takes small but mighty steps toward revolutionising narcolepsy.

Alkermes’ narcolepsy drug candidate alixorexton significantly improved how long patients can stay awake in a mid-stage trial, but a high rate of vision-related side effects could cause trouble for the treatment. Back in July, the biotech said that alixorexton met the Phase 2 trial’s primary endpoint of improvement in sleep latency. Results across all three dose cohorts were statistically significant, Alkermes said at the time, but it didn’t share details from the trial, called Vibrance-1. New, fuller data were presented at the World Sleep Congress in Singapore on Monday. They showed that patients given 8 mg of alixorexton stayed awake for an average of 28 minutes in the Maintenance of Wakefulness Test (MWT), at six weeks of treatment. The test involves getting patients to lie down in a dark, quiet room at regular intervals over eight hours and measuring the time it takes for them to fall asleep. For comparison, patients stayed awake for just three minutes when they first entered the trial. The study enrolled 92 people with narcolepsy type 1 (NT1), which causes daytime sleepiness and on-and-off muscle weakness. One worry, however, could be the drug’s side effect profile. In the trial, almost 30% of patients on the 8 mg dose — the trial’s highest — reported blurry vision. In the 6 mg group, 5% had blurry vision and 9% did in the 4 mg group. Last week, Leerink analysts said visual disturbance rates of more than 10% would likely concern investors and hurt the drug’s chances. In an interview ahead of the medical meeting, Alkermes CEO Richard Pops told Endpoints News that there were no changes in patients’ eye exams and said the blurry vision events were generally mild and resolved within three days. Efficacy was also seen at lower doses in Vibrance-1, which could help the company manage side effects. Pops said Alkermes plans to advance multiple doses into late-stage development. Patients given 6 mg of alixorexton stayed awake for an average of 26 minutes, and for an average of 24 minutes on 4 mg of alixorexton, according to Monday’s data. A healthy person can typically stay awake for at least 20 minutes, according to the company. Standard of care for narcolepsy type 1 usually extends the time it takes to fall asleep by “single-digit numbers of minutes, maybe 10 or 11 minutes at best,” Pops said. “So in terms of the aggregate amounts of additional wakefulness during the day, [the alixorexton data are] really significant.” Alkermes will get more data before deciding on a final development path: It doesn’t expect to finalize registrational trial plans for alixorexton with the FDA until it has results from a separate Phase 2 trial in narcolepsy type 2 (NT2), which is set to read out later this fall. Alixorexton is an orexin agonist. The class also includes Takeda’s oveporexton and Centessa Pharmaceuticals’ ORX750, and works by mimicking a neuropeptide called orexin that regulates wakefulness and is missing in people with narcolepsy. On Monday, Takeda shared detailed results from two Phase 3 trials of oveporexton in narcolepsy type 1 at the congress, showing that patients were able to stay awake for around 22 to 25 minutes in the MWT. Alkermes’ trial also looked at cataplexy, or muscle weakness, as a key secondary endpoint. There, only the middle of the three doses was successful. The 6 mg group achieved a weekly cataplexy rate of 0.31 versus placebo (p=0.01). The 4 mg dose produced a 0.49 rate and the 8 mg dose produced a 0.64 rate, both of which were not statistically significant. The lack of significance in the higher dose group worried some observers back in July, as they had expected cataplexy rates to improve in correlation with increasing doses. The lack of dose response likely “has more to do with the way you count the cataplexy events,” Pops said. Some patients in the trial would register bouncing their knee up and down 20 times while watching a movie as a single cataplexy event, while others would report it as 20 events, he explained. Pops added the company plans to standardize a method for counting cataplexy events before advancing to Phase 3.