Keros Therapeutics adjusts TROPOS trial of cibotercept amid safety concerns

Keros Therapeutics, Inc., a clinical-stage biopharmaceutical company, has announced significant changes to its Phase 2 TROPOS trial evaluating cibotercept safety concerns in patients with pulmonary arterial hypertension (PAH). Following the identification of unanticipated adverse events, the company has suspended dosing in two of the treatment arms while continuing with a lower-dose group. This decision underscores Keros Therapeutics’ commitment to patient safety and its intent to collaborate closely with the U.S. Food and Drug Administration (FDA) and other global regulatory bodies.

Safety Concerns Prompt Dose Adjustments

The TROPOS trial was designed to assess cibotercept’s effects in combination with standard pulmonary arterial hypertension therapies, but the identification of pericardial effusion in the 3.0 mg/kg and 4.5 mg/kg treatment groups led to a halt in those arms. The cibotercept safety concerns prompted a careful review by the independent Data Monitoring Committee (DMC), which advised continuing treatment in the 1.5 mg/kg arm.

Despite the pause in higher-dose groups, dosing continues for the 1.5 mg/kg treatment arm, following a comprehensive risk-benefit analysis. Keros Therapeutics confirmed that the trial remains fully enrolled, and safety and efficacy data collection across all groups will proceed.

What Is Cibotercept and Why Does It Matter?

Cibotercept, designed to inhibit the signaling of key bone morphogenetic protein pathways, targets transforming growth factor-beta (TGF-β) ligands like activin A, activin B, and myostatin. These proteins contribute to smooth muscle hypertrophy and fibrosis in diseases like pulmonary arterial hypertension. By blocking these pathways, cibotercept seeks to restore bone morphogenetic protein signaling, which is often impaired in PAH due to mutations in BMP receptors.

Expert Insights: Patient Safety in Focus

The suspension of higher-dose treatment arms highlights Keros Therapeutics’ strong commitment to patient safety, ensuring that the trial can proceed with caution. Experts agree that halting doses in response to cibotercept safety concerns is a prudent step to ensure that the therapy can proceed without compromising patient well-being. The continuation of the 1.5 mg/kg treatment group allows Keros to continue investigating the potential of cibotercept while keeping patient safety at the forefront.

Timeline and Next Steps

Keros Therapeutics has notified the FDA and is working with other global regulatory authorities to address the findings of the trial. The company remains on track to present topline data from all treatment groups in the second quarter of 2025. Updates on the safety investigation will be provided as more information becomes available.

Broader Implications

For the biopharmaceutical industry, this situation highlights the complexities of developing treatments for rare, severe diseases like pulmonary arterial hypertension. Although cibotercept shows potential to address disrupted bone morphogenetic protein signaling in PAH, its path to approval will depend on proving its safety and efficacy in ongoing trials.