Takeda awakens the narcoleps market with top-notch medicines, but Elkmes is on the heels
No biological measures to be sober. In a clinical trial of anesthesia, the patient lies in a dark lab while the clinician spends minutes until sleep comes. The average time in the four tests is the result. Sarah Sheikh, regional department and global development leader for neuroscience therapy, said the maintenance of this maintenance test may be the most boring and artificial of all clinical tests, but it is the standard method for evaluating disease medications.
The main goal that Takeda drug may first be achieved in new intestinal female drugs is the main goal of a two-stage clinical trial, with statistically significant results suggesting that it can help participants stay longer in those dark rooms. But this is what it means to patients in their daily lives: get up from the sofa, leave home, go to the gym, interact with family and friends, and then return to school or work.
“In a sense, this brings people back into society to live dedicated and productive lives,” Sheikh said in an interview.
The drug’s result is Oveporexton, introduced on Monday in Singapore’s 2025 World Sleep. Takeda is now aiming to regulate drug submissions in the U.S. and around the world during the current fiscal year. The pharmaceutical giant estimates that twice-daily drugs can reach global peak revenue of $2 billion to $3 billion.
There are two main forms of sleeping illness. Takeda developed Overporexton for Type 1 Intestinal Polyworm (NT1), a form accompanied by sudden muscle weakness events called cataplexy. The rare NT2 is similar to the first type, but it is not practiced at will.
The narcolepsy drugs currently available are older drugs for treating the symptoms of the disease – excessive sleepiness during the day and difficulty falling asleep at night. These drugs cannot solve the root cause of enteral disease, which is the loss of Orexin, a neuropeptide that regulates the sleep/wake cycle. Oveporexton is an oral small molecule designed to withstand beetletin, bind to the Orexin 2 receptor, and activate them to restore the lost activity when natural Orexin lowers levels fall.
During maintenance of maintenance sobriety tests (MWT), the normal range of people without seizure madness is staying in a dark room for 20 minutes or more. Takeda evaluated Oveporexton in two placebo-controlled phase 3 clinical trials, with a total of 273 participants. In studies testing low and high doses of excessive protein, low doses helped patients maintain an average of 19.3 minutes at 12 weeks; high doses were better at 21.8 minutes. In trials that evaluate only high doses, the results were even better, as the study medication helped patients stay on average for 24.6 minutes. Placebo results in both studies were 4.5 minutes or less. Sheikh noted that Oveporexton's results are also the best narcotic drug currently, which can help patients stay awake for 3 to 10 minutes in MWT.
Study participants were also evaluated based on the Sleepiness Scale, in which the patient scored for a week’s sleepiness level – a lower score meant less sleepiness. Takeda reported that nearly 85% of participants receiving high doses of Oveporexton scored comparable to those of healthy people. Regarding the measurement of the bounce path, the median bounce can increase from zero at baseline to four days of week 12 every week. There was no increase in this day reported in the placebo group.
“This is the first time in this disease, and anyone can show such a huge effect in every symptom that affects patients with higher statistical significance in NT1 patients,” Sheikh said.
Takeda said Oveporexton is tolerated by patients. The most common adverse events associated with treatment are frequent or urgency and insomnia. Both side effects begin in the first few days of treatment and resolve within about a week. Importantly, there are no signs of hepatotoxicity. Takeda's earlier efforts to develop Orexin Agonist stopped due to liver complications.
While Takeda's NT1 drug may be a new intestinal p poison, competition is coming. Alkermes has reached medium-term development using an Orexin agonist called Alixorexton. In a 2024 interview, COO Blair Jackson said the dose once a day and the high alertness of using this brain-penetrating drug may offer top-notch potential in NT1. But some investors are worried about blurred vision, which has already emerged when testing alkaline pills. In the 2-stage results presented in World Sleep, alkaline drugs measured statistically significant MWT results after six weeks. Like Takeda's medications, side effects that are resolved within a week are usually reported. Alkermes said blurred vision is usually resolved within three days.
During a call with analysts on Monday, Sheikh said Takeda searched for visual impairment and found that the problem was balanced between treatment and placebo arm. She added that vision problems “are definitely not a problem for us.”
Leerink Partners analyst Marc Goodman said in a note sent to investors that the higher incidence of visual impairment is driven by higher doses of Alixorexton, so the company believes Alkermes can basically get the same efficacy, but with lower complications with two lower doses of the drugs. Goodman wrote that the efficacy of alkaline drugs “seems to be a little better than Takeda’s, but not much better.” He said, however, flexibility once daily dosing and dosing should be an advantage for alkaline drugs, as the company aims to be the second player in the Orexin agonist market.
Sheikh said on the call that Takeda actually conducted a test in Phase 2. But twice a day imitates Orexin's natural dose more closely. In addition, twice-daily medications provide doctors and patients with greater dose flexibility, which can provide personalized treatment options, she said. With this flexibility in mind, Takeda will seek regulatory approval for both Oveporexton doses.
Takeda aims to expand its Orexin efforts beyond NT1. Another drug, TAK-360, is in a Phase 2 NT2 and idiopathic hypertension test. Other Orexin agonists are in the development stage of other sleep/wake conditions. The company is also developing drugs targeting other physiological processes regulated by beetle receptors such as breathing, mood and metabolism.
Other companies developing Orexin receptor agonists include Centessa Pharmaceuticals, which has raised ORX750 to a Phase 2 test in NT1, NT2 and idiopathic Hypersomnia. Meanwhile, Eisai provides the first phase of world sleep results for NT1 drug candidate E2086.
Photo: Roos Koole, Getty Images
