Takeda stops phase 2 post-anesthesia recovery trial over slow enrollment

Takeda has stopped (PDF) a phase 2 trial of danavorexton because of slow enrollment, marking another twist in the development of a orexin-2 receptor agonist franchise that has experienced ups and downs.

Danavorexton, also known as TAK-925, was at the vanguard of Takeda’s work to show orexin-2 receptor agonists can move the needle in indications including narcolepsy. Starting in 2017, the company put the intravenous drug candidate through a series of early-phase trials and, as it increasingly focused on oral prospects in narcolepsy, looked at other indications for danavorexton.

Takeda identified post-surgical patients with obstructive sleep apnea who were at high-risk of developing respiratory complications in hospital post-anesthesia care units as one population that may benefit from the drug. However, a phase 2 trial in the setting ran into challenges.

A Takeda spokesperson said the trial “presented challenges for enrolling participants, data collection and other operational difficulties.” Because of those difficulties, Takeda “determined that the study was no longer operationally feasible,” the spokesperson said. The decision to stop the study wasn’t a result of any new safety signals, and the benefit/risk profile of danavorexton is unchanged.

“We are actively evaluating potential next steps for the development of danavorexton in other indications aimed at facilitating enhanced recovery for patients in a hospital setting given its wake promoting properties and ability to stimulate respiratory function as demonstrated by preclinical and early clinical data,” the spokesperson said.

Takeda set out to enroll 180 people to assess whether danavorexton can help improve people's breathing in the recovery room after abdominal surgery. The company was aiming to reach the primary completion of the trial in one year when it started the study in May 2023, according to ClinicalTrials.gov, but pushed the target back to January 2025 earlier this year.

Months after it originally planned to finish the trial, Takeda was still less than one-quarter of the way to its enrollment goal. The company ended the trial one month ago having enrolled 41 patients.

Takeda disclosed the termination on ClinicalTrials.gov and through its earnings report this week. The company said it stopped the study because of enrollment challenges, saw no new safety findings and is exploring alternative indications. 

Editor's note: This story was updated at 10 am on Oct. 3 to include comments from Takeda.