China Center of Drug Evaluation (CDE) Grants Breakthrough Therapy Designation to Takeda’s TAK-994

In September 2021, Takeda China announced that TAK-994, an Oral Orexin Agonist in Clinical Development for Narcolepsy Type 1 (NT1), has been granted breakthrough drug (BTD) by Center of Drug Evaluation (CDE) of the National Medical Products Administration, for the treatment of patients with narcolepsy type 1 (NT1).  Up to now, no drug has yet to be approved for this indication in China, and patients have extremely urgent clinical needs.

Narcolepsy is a rare, acquired chronic neurological disorder that alters the sleep-wake cycle of patients. Excessive daytime sleepiness (EDS) is a hallmark symptom of narcolepsy, and patients may suddenly shift from wakefulness to rapid eye movement (REM) sleep. These sleep phenomena may include cataplexy (the sudden loss of muscle tone in response to a strong emotion), hypnagogic and hypnopompic hallucinations (sensory events that occur at the transition from wakefulness to sleep or from sleep to wakefulness), and sleep paralysis, and frequent attacks of disrupted nighttime sleep (DNS), or waking up frequently throughout the night.

Narcolepsy is classified into two subtypes, type 1 narcolepsy (NT1) and type 2 narcolepsy (NT2). NT1 accounts for approximately 70% of all narcolepsy cases. Patients with narcolepsy, especially NT1, often suffer from related symptoms in their daily lives, which might mean routinely falling asleep at work or in school. The disease seriously affects their quality of life, and even has a significantly negative social impact on the individual patients.

Orexin, a neuropeptide or signaling molecule in the brain, has been identified as the master regulator of sleep-wake states. Recent research has suggested that orexin receptors are linked to arousal, wakefulness and energy homeostasis. The destruction of orexin-producing neurons in the brain is the underlying cause of Narcolepsy Type 1.

TAK-994 is a new oral orexin 2 receptor (OX2R) agonist developed by Takeda for the treatment of narcolepsy, and its development is the first approach that addresses the underlying orexin deficiency that causes this disorder[1]. Currently, TAK-994 is being evaluated in the phase 2 clinical trial. Early and preliminary clinical data indicated that TAK-994, as an oral orexin agonist, can substantially improve the objective and subjective measurements of daytime wakefulness in NT1 patients. In July 2021, the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to TAK-994. Right after the FDA’s approval, within just two months, CDE also granted BTD to TAK-994 in China, which again proved the “China speed” of Takeda China’s simultaneous drug development and registration progress with global.

From clinical development to NDA approval, the BTD would potentially accelerate the availability to Chinese patients, If approved, TAK-994 may become an innovative treatment to address the underlying pathophysiological cause of narcolepsy, i.e. the lack or reduction of Orexin peptide in the brain in NT1. 

 

Promomat Code: C-ANPROM/CN/GEN/0058

Review Date: 09.2021

 

[1] A Study of TAK-994 in Participants With Narcolepsy With or Without Cataplexy (Narcolepsy Type 1 [NT1] or Narcolepsy Type 2 [NT2]). ClinicalTrials.gov. Published April 1, 2021. https://clinicaltrials.gov/ct2/show/NCT04096560