Keros Therapeutics, Inc. has announced the discontinuation of its Phase 2 TROPOS trial evaluating cibotercept (KER-012) for the treatment of pulmonary arterial hypertension (PAH) after new safety signals emerged. The company voluntarily halted all dosing in the trial, including the 1.5 mg/kg and placebo treatment arms, due to the observation of pericardial effusion adverse events. This decision follows a previous halt of the 3.0 mg/kg and 4.5 mg/kg treatment arms announced in December 2024 due to similar safety concerns.
The TROPOS trial was a randomized, double-blind, placebo-controlled study designed to assess the efficacy and safety of cibotercept in combination with background therapy in PAH patients. The primary objective was to evaluate the effect of cibotercept on pulmonary hemodynamics compared to placebo, while a key secondary objective was to assess its impact on exercise capacity.
Safety Concerns Lead to Trial Termination
The decision to halt the trial was based on an ongoing safety review that revealed new cases of pericardial effusion, a condition characterized by the accumulation of excess fluid around the heart. Pericardial effusion can lead to serious complications, including cardiac tamponade, which can be life-threatening. Jasbir S. Seehra, PhD., Chair and CEO of Keros, stated, "While we are disappointed in this new development, patient safety is always our top priority."
Cibotercept Mechanism of Action
Cibotercept is designed to bind to and inhibit the signaling of TGF-β ligands, including activin A, activin B, and myostatin, which stimulate smooth muscle hypertrophy and fibrosis. Keros hypothesized that by inhibiting these ligands, cibotercept could increase bone morphogenic protein (BMP) signaling, addressing the reduced BMP signaling often associated with PAH due to inactivating mutations in BMP receptors.
Future Plans
Despite the trial's early termination, Keros Therapeutics plans to present topline data from all treatment arms in the second quarter of 2025. Patients enrolled in the TROPOS trial will continue to be monitored through the end-of-trial visits. The company has notified investigators, the U.S. Food and Drug Administration (FDA), and other relevant regulatory authorities about the decision.
Impact on Keros Therapeutics
The termination of the TROPOS trial represents a setback for Keros Therapeutics, particularly as cibotercept was being developed as a potential competitor to MSD's Winrevair (sotatercept), a fast-growing PAH therapy. Analysts suggest that the safety concerns are likely specific to cibotercept in the context of pulmonary arterial hypertension. The company is also deprioritizing the development of KER-065 in obesity, focusing instead on neuromuscular disorders such as Duchenne muscular dystrophy.
