Takeda Pharmaceutical’s TAK-994 has recently received breakthrough therapy designation (BTD) by the US Food and Drug Administration (FDA) for the treatment of excessive daytime sleepiness (EDS) in patients with narcolepsy type 1 (NT1). The potential approval of TAK-994 could lead to the first treatment that increases orexin activity in patients with narcolepsy, says GlobalData, a leading data and analytics company.

Christie Wong, Pharma Analyst at GlobalData, comments: “The narcolepsy therapies used to date are only able to alleviate the symptoms associated with the condition. The current treatment landscape for narcolepsy consists of stimulant drugs and a limited number of non-stimulant drugs with modest efficacy as many narcolepsy patients do not respond to the medications. There is a great unmet need for more efficacious treatments for sleepiness symptoms, as EDS is generally the most common and disabling symptom of narcolepsy.”

It is known that the pathophysiology of narcolepsy is characterized by a loss of orexin producing neurons in the brain. TAK-994 has agonist activity at orexin-2 receptors (OX2R), which is important for regulation of sleep and arousal. TAK-994 has the potential to address the unmet need by targeting the cause of the disease, which would give it a competitive edge over the marketed symptom-base therapies. However, TAK-994 will need to demonstrate strong efficacy in the ongoing Phase II studies (TAK-994-1504, NCT04820842 and TAK-994-1501, NCT04096560) and in a larger Phase III trial. GlobalData forecasts that TAK-994 will generate global sales of $654M by 2027.

Wong adds: “TAK-994 is likely to compete with NLS Pharmaceutics’ Quilience (mazindol ER), which is also in Phase II development. Quilience has a dual mechanism of action, targeting OX2R and it is a monoamine reuptake inhibitor like the other stimulants used to treat narcolepsy. Quilience received orphan drug designation for narcolepsy in the EU and US in 2015 and 2016, respectively.

Moreover, earlier this month, the FDA has accepted NLS Pharmaceutics’ investigation new drug application (IND) for Quilience, enabling NLS to initiate Phase IIa trials to assess the safety and efficacy of Quilience in patients with narcolepsy. However, mazindol is a scheduled IV controlled substance and has been linked with several safety concerns due to the sympathetic activity of mazindol and it has been associated with cardiac problems. As such, opportunities remain in the narcolepsy market for safe and effective treatments for EDS.”