New Safety Signals Force Keros to Fully Terminate Mid-Stage PAH Study

 

Taken together with Keros’ recent pivot away from obesity, the termination of its pulmonary arterial hypertension study could lead to a “difficult path ahead” for Keros, according to Guggenheim analysts.

Keros Therapeutics on Wednesday announced that it will completely discontinue the Phase II TROPOS study of its investigational fusion protein cibotercept in pulmonary arterial hypertension after an ongoing safety review found new signals of concern.

The news comes on the heels of another announcement from the company that Keros that it would “deprioritize” the development of its activin receptor ligand trap KER-065 in obesity. “Given the updates on the PAH front, as well as update and management’s recent announcement that they are deprioritizing the development of KER-065 in obesity . . . we believe the company and stock has a difficult path ahead, at least in the near-term,” Guggenheim Partners analysts wrote in an investor note on Wednesday morning.

Today’s announcement is not the first trouble shared about the TROPOS trial. Keros last month said it had suspended dosing in the 3-mg/kg and 4.5-mg/kg arms of the study due to “unanticipated” incidences of pericardial effusion, an adverse reaction characterized by the dangerous build-up of fluid around the heart. The company at the time did not clarify if the complications were related to cibotercept or not.

Now, Keros has revealed that new cases of pericardial effusion were detected in TROPOS, which pushed the biotech to “voluntarily” stop all dosing in the trial, including in the 1.5-mg/kg and placebo groups. “The TROPOS trial is being terminated early,” Keros noted in its announcement, adding that it will continue to monitor patients through end-of-trial visits. The company expects to present topline data from TROPOS in the second quarter of 2025.

“[While] the exact reason for the development of these pericardial effusions remains unknown,” it is likely that the complications are “specific to cibotercept” in pulmonary arterial hypertension (PAH), Guggenheim wrote.

Truist Securities also weighed in on Keros’ discontinuation of TROPOS, calling it “incrementally negative” in an investor note.

The development comes after Keros just last week revealed the deprioritization of KER-065 in obesity. As part of a sweeping portfolio management effort, Keros instead plans to focus its efforts and resources on testing KER-065 in neuromuscular disorders, particularly Duchenne muscular dystrophy, according to the compay’s corporate presentation.

At the beginning of the year, Keros had announced plans to advance KER-065 for obesity, and that it had already launched a two-part randomized, double-blinded, placebo-controlled Phase I study in this indication. Topline data from this study are expected in the first quarter of 2025, which Keros will use to inform the future development of the candidate in neuromuscular indications.

https://www.biospace.com/drug-development/new-safety-signals-force-keros-to-fully-terminate-mid-stage-pah-study