Alkermes has reported another phase 2 win for its narcolepsy drug candidate, succeeding where Takeda failed to maintain its hopes of being first to market in the indication.
The trial randomized 93 people with narcolepsy type 2 (NT2) to receive one of three doses of alixorexton or placebo. After eight weeks of once-daily oral dosing, Alkermes saw significant improvements on a test of wakefulness on the top two doses of alixorexton compared to placebo, achieving one of its co-primary endpoints. Only the top dose hit the other primary endpoint, which tested excessive daytime sleepiness.
No patients on alixorexton had serious treatment-emergent adverse events or clinically meaningful, treatment-related changes on ophthalmic exams. Eye safety has been a focus since Jazz Pharmaceuticals stopped a phase 1 trial of its narcolepsy prospect JZP441 in 2023 over reports of “visual disturbances.”
Alixorexton, like JZP441, is an orexin 2 receptor (OX2R) agonist. Dealing with the safety signal, Jazz is still back in phase 1. But Alkermes faces more advanced rivals for the narcolepsy market. Takeda is ready to seek approval for its lead OX2R asset oveporexton in narcolepsy type 1 (NT1) patients. Alkermes posted a win for alixorexton in NT1 in July.
Takeda halted development of oveporexton in NT2 last year, leaving its hopes of challenging Alkermes in the indication on the phase 2 TAK-360. Centessa Pharmaceuticals has shown ORX750 could be a threat to Alkermes in NT1 and NT2, with the company recently sharing phase 2a data on the OX2R agonist in both indications.
Guggenheim Securities analysts said in a note to investors last week that Centessa executives “appeared confident” of starting a registrational study in the first quarter of next year. The timeline puts Centessa neck and neck with Alkermes, which is planning to start its global phase 3 program in the same quarter. Craig Hopkinson, M.D., Alkermes’ chief medical officer, discussed the phase 3 plans with analysts.
“We've always believed in the value of providing a range of doses to accommodate disease variability and patient preference. We are even more convinced of that now,” Hopkinson said on the call.
“The nuances and underlying trends of the data provide an opportunity to amplify the signal,” Hopkinson added. “In phase 3, we plan to advance a range of doses, including once-daily administration as well as split-dosing regimens.”
Alkermes has identified split dosing as a way to address the variability in wakefulness seen at some time points. While responses were consistent two and four hours after dosing, they began to diverge after six and eight hours. Hopkinson declined to answer an analyst’s question about the potential magnitude of the benefit of splitting the dose, citing “proprietary reasons.”