Oral Imatinib Falls Short in Pivotal PH-HFpEF Trial

What happened in the pivotal imatinib heart failure trial?

STAT News reported that the Tenax Therapeutics drug failed in a closely watched pivotal study. In clinical development, such an outcome generally means that the trial did not produce sufficient evidence to meet its prespecified objective, although complete data are needed before the magnitude and causes of the failure can be assessed.

Headline-level results cannot show whether responses differed among patient subgroups or whether adverse events and treatment discontinuations affected the findings. Clinicians and researchers will need the full efficacy, safety and statistical results before deciding what the study reveals about imatinib or the broader strategy of targeting pulmonary vascular remodeling in heart failure.

Why was imatinib being studied for PH-HFpEF?

Imatinib is a tyrosine kinase inhibitor established as a treatment for several cancers, but it is not approved for heart failure or pulmonary hypertension associated with left-heart disease. Its inhibition of platelet-derived growth factor receptor signaling created interest in whether it might counter the cellular proliferation and vascular remodeling involved in some forms of pulmonary hypertension.

The earlier randomized IMPRES study evaluated imatinib in pulmonary arterial hypertension, a condition that differs biologically and clinically from PH-HFpEF. Although that trial found improvements in some exercise and hemodynamic measures, tolerability and serious safety concerns limited enthusiasm. Those findings could not establish that imatinib would benefit patients whose pulmonary hypertension arises from elevated left-sided heart pressures.

What does the trial failure mean for patients with PH-HFpEF?

PH-HFpEF occurs when heart failure with preserved ejection fraction is accompanied by increased pressure in the lung circulation. Management typically focuses on congestion, blood pressure and relevant conditions such as obesity, diabetes, atrial fibrillation and sleep-disordered breathing. Major cardiology guidelines caution that treatments approved for pulmonary arterial hypertension should not automatically be applied to pulmonary hypertension caused by left-heart disease.

Patients should not seek cancer-formulation imatinib for this cardiovascular condition or alter prescribed treatment because of the trial report. The next scientific steps include publication of the complete results, analysis of safety and subgroup data, and evaluation of whether different targets or more precisely selected patient populations could produce better outcomes.