Keros Therapeutics Pauses Cibotercept Dosing in Higher Dose Arms of Phase 2 PAH Trial Due to Pericardial Effusion
Key Insights
Keros Therapeutics halts dosing in the 3.0 mg/kg and 4.5 mg/kg arms of its Phase 2 TROPOS trial of cibotercept for pulmonary arterial hypertension (search) (PAH (search)) after detecting pericardial effusion (search).
The decision follows a safety review and consultation with an independent Data Monitoring Committee; dosing continues in the 1.5 mg/kg arm.
Keros is working with investigators and the FDA to understand the findings and expects to share topline data from all trial arms in Q2 2025.
Keros Therapeutics, Inc. has voluntarily suspended dosing in two arms of its Phase 2 TROPOS trial evaluating cibotercept (KER-012) for pulmonary arterial hypertension (search) (PAH (search)) following the observation of pericardial effusion (search) in some patients. The TROPOS trial is assessing cibotercept in combination with background therapy.
The decision, announced December 12, 2024, affects the 3.0 mg/kg and 4.5 mg/kg dose arms of the study. Dosing continues in the 1.5 mg/kg treatment arm after a risk and benefit assessment conducted by an independent Data Monitoring Committee (DMC) and a select group of unblinded individuals at Keros. The company has notified study investigators and the U.S. Food and Drug Administration (FDA) about the findings.
Safety Concerns Lead to Dosing Halt
Pericardial effusion (search), characterized by abnormal fluid accumulation around the heart, can interfere with normal heart function if excessive. Keros is investigating whether the observed cases are linked to cibotercept. "Patient safety is our top priority," said Jasbir S. Seehra, Ph.D., Chair and CEO of Keros, in a statement. The company is working to understand these unanticipated findings.
TROPOS Trial Design and Next Steps
The TROPOS trial is a randomized, double-blind, placebo-controlled Phase 2 study evaluating cibotercept in combination with background therapy in PAH (search) patients. The primary objective is to assess the effect of cibotercept on pulmonary hemodynamics compared to placebo. A key secondary objective is to evaluate the effect of cibotercept on exercise capacity.
Keros intends to continue collecting safety and efficacy data from all treatment arms and still anticipates presenting topline data from the trial in the second quarter of 2025. The company plans to provide additional updates as the investigation progresses.
Cibotercept Mechanism of Action
Cibotercept is a modified activin (search) receptor fusion protein designed to bind to and inhibit the signaling of TGF-β ligands, including activin A, activin B, and myostatin (search). Keros believes that cibotercept has the potential to increase BMP signaling, which is often reduced in PAH (search) due to inactivating mutations in BMP receptors.
Impact on Keros Therapeutics
The news of the dosing halt led to a significant drop in Keros Therapeutics' stock price. Truist Securities analysts anticipate continued pressure on the stock until the safety concerns are resolved and further data is available. This development comes shortly after Keros's recent agreement with Takeda (search), where Keros received $200 million upfront for the rights to elritercept, an activin (search) inhibitor being trialed for anemia (search) in blood cancers.