Seralutinib Shows Mixed Results in Phase 3 PAH Trial, Winrevair Benefits Heart Failure-Related PH

Topline results from a phase 3 trial evaluating seralutinib for pulmonary arterial hypertension showed the study did not meet its primary endpoint threshold, though the investigational therapy demonstrated greater activity in patients with more advanced disease. Meanwhile, newly published data from a separate trial showed Winrevair significantly reduced pressure in the lungs' blood vessels among adults with pulmonary hypertension associated with heart failure.

In the PROSERA study, patients with WHO functional class II or III PAH were randomly assigned to receive inhaled seralutinib or placebo twice daily for up to 48 weeks. The primary endpoint was the change in distance achieved on the 6-minute walk test at week 24. In the overall study population, findings showed the study did not meet the prespecified alpha threshold of 0.025 on the primary endpoint. At week 24, the median change in 6MWD from baseline was +28.2 meters with seralutinib vs +13.5 meters with placebo.

Notably, in the prespecified intermediate and high-risk subgroup, a +20.0 meter placebo-adjusted improvement in 6MWD was observed, with significant improvements seen in 3 of the 4 key secondary endpoints. The company stated that these data support the conclusion that seralutinib demonstrated greater activity in patients with more advanced disease, which is even more impressive given how heavily treated the PROSERA population was, including 55% of patients on triple or quadruple background PAH therapy and 61% on background prostacyclin therapy.

Regarding safety, the most common adverse event reported with seralutinib was cough. Thirteen percent of seralutinib-treated patients experienced transaminase elevations of 3 times or greater than the upper limit of normal compared with 1% of placebo patients. Based on the PROSERA findings, Gossamer Bio plans to meet with the Food and Drug Administration to discuss next steps for seralutinib in PAH.

In a separate development, treatment with Winrevair significantly reduced pressure in the lungs' blood vessels among adults with a form of pulmonary hypertension associated with heart failure, according to newly published data. The injection therapy, approved in the U.S. for people with pulmonary arterial hypertension, was tested in the Phase 2 CADENCE clinical trial as a possible treatment for individuals with combined post- and precapillary and heart failure with preserved ejection fraction.

The CADENCE trial enrolled 164 adults with CpcPH-HFpEF. Participants were randomly assigned to receive Winrevair at one of two maintenance doses, or a placebo, administered every three weeks for 24 weeks. The study's main goal was to show that Winrevair would reduce pulmonary vascular resistance, a measure of how difficult it is for the heart to pump blood to the lungs. The trial hit this goal: Median PVR decreased by 0.67 and 0.33 Wood units in the low- and high-dose Winrevair groups, respectively. By contrast, in patients given the placebo, median PVR increased by 0.26 Wood units.

Improvements with Winrevair relative to the placebo were also observed in other measures of lung blood vessel pressure, namely mean pulmonary arterial pressure and pulmonary arterial wedge pressure. Treatment was also associated with benefits in a range of other secondary endpoints, including reductions in levels of a heart damage marker called NT-proBNP and delayed clinical worsening. Improvements were also seen in six-minute walk distance, which is a common measure of exercise capacity.

Data from CADENCE indicated that Winrevair was generally well tolerated, with a safety profile similar to what is seen in PAH patients. The company is now planning a Phase 3 clinical trial to further evaluate Winrevair as a potential treatment for CpcPH-HFpEF.