Dr Rebecca EvansRebecca Evans, MD, MSc
Recent results of a phase 1 clinical proof of concept study suggest that TAK-925, an investigational treatment for patients with narcolepsy type 1 developed by Takeda Pharmaceuticals, is well tolerated and is associated with increased wakefulness at night compared with placebo.

Data presented at the World Sleep 2019 Biennial Congress in Vancouver, Canada, demonstrated marked changes on the Maintenance of Wakefulness Test (MWT) for patients treated with TAK-925, who had MWT scores of 22.4 mins for TAK-925 at 5 mg (n = 6), 37.6 mins at 11.2 mg (n = 4) and 40 mins at 44.8 mg (n = 4) compared with 2.9 mins for placebo (n = 13).

To learn more about the selective orexin type-2 receptor (OX2R) agonist, NeurologyLive spoke with study author Rebecca Evans, MD, MSc, senior director, Global Clinical Science, at Takeda. She offered her perspective on the care gaps that TAK-925 may be able to fill, and the ongoing work with the compound.

NeurologyLive: What potential gaps in care might TAK-925 fill if it’s successful in further studies?

Rebecca Evans, MD, MSc: Narcolepsy type 1 is caused by loss of orexin-producing neurons, and as an orexin receptor 2 agonist, TAK-925 targets this underlying orexin deficiency. Current medications for narcolepsy usually produce good but often partial improvements in the symptoms of narcolepsy. For example, even with "optimal medications," many patients still experience moderate sleepiness which can substantially impact their performance in work, school, and relationships. I anticipate that an orexin agonist would be more effective than current medication options and additional studies need to be completed. 

Have any data thus far been particularly interesting? 

TAK-925 is the first orexin agonist to be tested in people with narcolepsy type 1. The small study utilized the Maintenance of Wakefulness Test (MWT), a standard measure of sleepiness and found that with higher doses of TAK-925, narcolepsy patients were often able to stay awake for the entire duration of the test. Currently available medications produce small to moderate improvements on the MWT.

What makes TAK-925 unique compared to other narcolepsy type 1 treatments?

As the first orexin agonist to be evaluated in patients with narcolepsy, TAK-925 addresses the fundamental problem in narcolepsy - loss of orexin signaling. Based on the early data, it appears effective and more trials are underway. Orexin agonists are likely to be a real breakthrough in treating narcolepsy.

What’s next for this therapy in its clinical development?

We are currently recruiting for a Phase 1 TAK-925 study in Japan of healthy adults and individuals with narcolepsy. This study is investigating a daily administration of TAK-925 for 7 consecutive days, versus the single-dose administration that was investigated in the recently completed Phase 1 study, results of which were presented at the World Sleep 2019 Congress.
 
We have also initiated start-up activities for 3 new clinical studies in the US and Japan across a variety of sleep-wake disorders, including narcolepsy type 1, idiopathic hypersomnia (IH), and residual excessive daytime sleepiness (EDS) in obstructive sleep apnea (OSA). We have initiated start-up activities for 2 separate phase 1b studies, with one study investigating TAK-925 in individuals with OSA experiencing EDS (in US only) and another study investigating TAK-925 in individuals with IH (US and Japan). In addition, we have initiated start-up activities for a phase 1 clinical study investigating our oral selective OX2R agonist, TAK-994, in individuals with narcolepsy type 1 (US and Japan).
 
Transcript edited for clarity.
REFERENCE
New Data Presented at World Sleep Congress Demonstrate Early Signs of Efficacy for TAK-925, a Selective Orexin Type-2 Receptor (OX2R) Agonist, in Patients with Narcolepsy Type 1 [press release]. Cambridge, MA: Takeda Pharmaceutical Company; Published September 25, 2019. businesswire.com/news/home/20190925005923/en/New-Data-Presented-World-Sleep-Congress-Demonstrate. Accessed October 5, 2019.