Takeda's OX2R Agonist TAK-994 Granted Breakthrough Therapy Designation in China for Narcolepsy Type 1

By | Pharma Insights

Today (August 26), the official website of the Center for Drug Evaluation (CDE) under China's National Medical Products Administration (NMPA) released a new notice indicating that TAK-994 tablets, an investigational drug by Takeda, is proposed for inclusion in the Breakthrough Therapy Drug list for the treatment of type 1 narcolepsy. Publicly available information shows that TAK-994 is an oral orexin-2 receptor (OX2R) agonist that has previously been approved for clinical trials in China for the treatment of narcolepsy. Earlier this month, the U.S. FDA also granted Breakthrough Therapy designation to TAK-994 for sleep disorder indications.

Screenshot source: CDE official website

Orexin is a neurotransmitter generally recognized as a primary regulator of the sleep-wake cycle. Research indicates that patients with narcolepsy type 1 experience a substantial loss of orexin-producing neurons in the brain. Therefore, agonists that activate the orexin type 2 receptor may substitute for endogenous orexin and activate wake-promoting signaling pathways. TAK-994, developed by Takeda, is designed to selectively target the orexin type 2 receptor and is currently being evaluated in a Phase 2 clinical trial.

In early August, Takeda announced that the US FDA granted Breakthrough Therapy designation to TAK-994 for the treatment of excessive daytime sleepiness in patients with narcolepsy type 1. Excessive daytime sleepiness is a hallmark symptom of narcolepsy type 1, characterized by an inability to maintain wakefulness and alertness throughout the day, resulting in falling asleep at inappropriate times.

It is reported that the granting of this breakthrough therapy designation is based on early and preliminary clinical data. These data indicate that Takeda’s investigational oral orexin agonist can significantly improve objective and subjective measures of daytime wakefulness in patients with narcolepsy type 1.

Meanwhile, the intravenous infusion formulation of this drug, TAK-925, also demonstrated efficacy in maintaining wakefulness in patients with NT1 in a Phase 1 proof-of-concept clinical trial.

In China, the clinical trial application for TAK-994 received implied approval from the CDE in September 2020. According to the Drug Clinical Trial Registration and Information Public Platform, a randomized, double-blind, placebo-controlled, multiple ascending dose oral administration study evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-994 in patients with narcolepsy (type 1 or type 2) with or without cataplexy is currently underway.

Image source: Screenshot from the official website of the Drug Clinical Trial Registration and Information Disclosure Platform

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Aug 26, 2021, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=25#

[2] Food and Drug Administration Grants Breakthrough Therapy Designation to Takeda’s Investigational Compound, TAK-994, an Oral Orexin Agonist in Clinical Development for Narcolepsy Type 1 (NT1). Retrieved August 1, 2021, fromhttps://www.businesswire.com/news/home/20210728005256/en

[3] Scanmmell (2001). Wakefulness: An eye-opening perspective on orexin neurons. Current Biology, DOI:https://doi.org/10.1016/S0960-9822(01)00466-3

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