Takeda said that the Phase 2 study of TAK-994 in narcolepsy type 1 (NT1) had to be ended prematurely because of hepatotoxicity in several patients.

The Japanese pharma company had to subsequently scrap the further development of the TAK-994 programme.

According to Takeda, the orexin receptor 2 (OX2R) agonist will not be pursued as a treatment for narcolepsy. However, it could indicate a biologic target for future development, said the Japanese firm.

The TAK-994-1501 Phase 2 study assessed the safety and efficacy of TAK-994 in patients aged 18 to 65 years with confirmed narcolepsy type 1.

During the trial, the participants were assigned randomly to receive twice-daily oral TAK-994 30mg, 90mg, 180mg, or placebo. The mid-stage trial featured 73 patients, of which 17 were on placebo, and the rest were subjected to the investigational drug.

The study’s primary endpoint was defined as the variation in mean sleep latency in minutes on the Maintenance of Wakefulness Test (MWT) from baseline to week eight.

The secondary endpoints included the change in treatment-emergent adverse events (TEAEs), weekly cataplexy rate (WCR), and Epworth Sleepiness Scale (ESS) score.

As per the findings, the OX2R agonist showed a statistically significant enhancement in daytime wakefulness.

On MWT, TAK-994 demonstrated a change in mean sleep latency to week eight by -2.5 minutes for placebo, 23.9 minutes, 27.4 minutes, and 32.6 minutes for the three doses, respectively.

Additionally, changes in ESS were observed with -2.1 for placebo, -12.2, -13.5, and -15.1 for the three doses, respectively.

Gui de Chauliac Hospital, Montpellier, France, department of Neurology sleep-wake disorders centre director Yves Dauvilliers, who served as one of the principal investigators of the TAK-994 study, said: “Although this study was not designed to compare TAK-994, the first-in-class oral OX2R agonist, with other narcolepsy drugs, its effectiveness on objective measures of wakefulness, self-reported assessment of daytime sleepiness, and frequency of cataplexy was impressive.

“However, TAK-994 was associated with hepatotoxicity, therefore studies with new well tolerated OX2R agonists are strongly requested.”

Takeda revealed that it is assessing another of its oral OX2R agonists in two Phase 2 placebo-controlled trials for the treatment of narcolepsy.