Keros Therapeutics has terminated development of its experimental pulmonary arterial hypertension (PAH) treatment cibotercept (KER-012) following safety concerns that emerged during the TROPOS Phase 2 trial. The company announced the decision after analyzing topline data showing dose-dependent pericardial effusions that led to early trial termination.
Trial Termination Due to Safety Signals
The TROPOS Phase 2 trial, which evaluated cibotercept in combination with background therapy in PAH patients, was progressively halted due to safety concerns. In December 2024, Keros voluntarily stopped the 3.0 mg/kg and 4.5 mg/kg treatment arms after observing pericardial effusions at those dose levels. The company subsequently halted all dosing in January 2025, including the 1.5 mg/kg and placebo arms, following additional pericardial effusion adverse events during ongoing safety reviews.
The analysis revealed a dose-dependent signal for pericardial effusions in the PAH population, with higher incidence rates and severity observed in the 3.0 and 4.5 mg/kg arms compared to the 1.5 mg/kg arm. Notably, the background rate of pericardial effusions in this trial exceeded those seen in randomized controlled trials of Merck's approved PAH treatment Winrevair (sotatercept).
Efficacy Results Fall Short
Beyond the safety concerns, cibotercept failed to demonstrate clinical benefit in key efficacy measures. The company reported no clinically meaningful improvement in pulmonary vascular resistance (PVR) or 6-minute walk distance (6MWD), two critical endpoints for PAH treatments. Keros noted that the ability to interpret 24-week data was limited due to incomplete treatment duration and trial visit participation following the early termination.
During the treatment period analyzed, no major signals were observed for hemoglobin increases, thrombocytopenia, bleeding events, or telangiectasias relative to placebo, indicating the safety profile was primarily characterized by the pericardial effusion concerns.
Corporate Restructuring and Future Plans
Following the program discontinuation, Keros is implementing significant organizational changes, reducing its workforce by approximately 45% from current levels to 85 full-time employees. The restructuring is expected to generate average annualized cost savings of approximately $17 million.
The company indicated it plans to evaluate potential development strategies for cibotercept in other indications following completion of its strategic alternative review process. This suggests Keros may explore applications beyond PAH for the investigational therapy, though specific indications were not disclosed.
The program termination represents a significant setback for Keros' pipeline and highlights the challenges in developing new treatments for PAH, a rare but serious condition affecting the pulmonary arteries. The safety profile observed with cibotercept, particularly the dose-dependent pericardial effusions, appears to have been the decisive factor in the discontinuation decision, even as the company continues to explore potential alternative applications for the drug.
