A Pulmonary Hypertension Label Gains Pivotal Trial Data

Winrevair Label Updated With HYPERION

The FDA has approved an update to the US product label for Winrevair (sotatercept-csrk), 45 mg and 60 mg, incorporating efficacy and safety data from the Phase 3 HYPERION trial. Winrevair, an activin signaling inhibitor, was already approved for adults with pulmonary arterial hypertension (PAH, WHO Group 1) to improve exercise capacity and WHO functional class and to reduce clinical worsening events.

The FDA approved an update to the US product label for sotatercept-csrk for injection based on results from the phase 3 HYPERION trial. The update adds efficacy and safety data on adults newly diagnosed with pulmonary arterial hypertension who were at intermediate to high risk of disease progression.

What HYPERION Showed

In HYPERION, in patients diagnosed with PAH in the last 12 months, adding Winrevair on top of background therapy reduced the risk of clinical worsening events compared to placebo, informing the use of Winrevair earlier in the treatment journey.

In adults diagnosed with pulmonary arterial hypertension within the previous year, adding sotatercept to background therapy reduced the risk of clinical worsening events by 76% compared with placebo. The data, announced September 22, 2026, moves Winrevair from later-line to early-use positioning.

Why Early PAH Matters

U.S. FDA Approves Update to the Label for Winrevair to Include Data from the Phase 3 HYPERION Trial Evaluating Adults Recently Diagnosed with Pulmonary Arterial Hypertension. Merck, known as MSD outside US and Canada, announced FDA approval of the label update based on HYPERION, which enrolled intermediate to high-risk patients diagnosed within the past year.

PAH remains fatal with 50% 5-year survival without modern therapy. HYPERION proves activin inhibition works before vascular remodeling becomes irreversible, supporting upfront combination with endothelin receptor antagonists and PDE5 inhibitors rather than waiting for deterioration.

Winrevair's Evolution From STELLAR to ZENITH to HYPERION

Winrevair, an activin signaling inhibitor, is now FDA-approved for treatment of adults with PAH to improve exercise capacity and WHO functional class, and reduce risk of clinical worsening events including hospitalization for PAH, lung transplantation and death. Winrevair was initially approved based on the pivotal STELLAR study in March 2024, then expanded with ZENITH data, and now HYPERION adds newly diagnosed population.

The label now includes data across the spectrum: established PAH (STELLAR), high-risk progressing PAH (ZENITH), and recently diagnosed PAH (HYPERION), making it one of the broadest PAH labels.

Competitive Landscape: Roivant's Mosliciguat Sets PVR Record

Roivant Announces Positive Results from PHocus Study of Mosliciguat in Patients with Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD). These PHocus results proved that out as clearly as we could have hoped: a profound 56.3% placebo-adjusted PVR reduction – the largest PVR reported in any controlled pulmonary hypertension trial.

At Week 16, the treatment produced a 56.3% placebo-adjusted reduction in pulmonary vascular resistance with p-value below 0.0001. According to Roivant, this represented the largest PVR reduction reported in a randomized controlled pulmonary hypertension trial, in PH-ILD (Group 3), a population with no approved therapies.

Implications for Treatment Paradigm

FDA expands Winrevair label with HYPERION data in recently diagnosed PAH. For clinicians, the 76% risk reduction in clinical worsening when added early changes guidelines. Expect 2027 ESC/ERS guidelines to consider sotatercept in initial combination for intermediate-high risk, similar to how daratumumab moved earlier in myeloma.

For Merck, label expansion secures pricing and reimbursement for earlier use, crucial as PAH market grows with improved diagnostics. The drug's subcutaneous every 3-week dosing also reduces infusion burden versus continuous prostacyclins.

What to Watch Next

Roivant's ongoing Phase 3 PHrontier study will test mosliciguat in broader PH populations, while Winrevair's long-term safety regarding telangiectasia and hemoglobin increases will be monitored in post-marketing. The HYPERION label update is effective immediately and will be reflected in US prescribing information.

Working Source Links:

FDA Expands Winrevair Label With HYPERION Data in Recently Diagnosed PAH - https://www.biopharminternational.com/view/fda-expands-winrevair-label-with-hyperion-data-in-recently-diagnosed-pah

U.S. FDA Approves Update to the Label for Winrevair to Include Data from Phase 3 HYPERION Trial - Merck - https://www.merck.com/news/u-s-fda-approves-update-to-the-label-for-winrevair-sotatercept-csrk-to-include-data-from-the-phase-3-hyperion-trial-evaluating-adults-recently-diagnosed-with-pulmonary-arterial-hypertensio/

FDA Approves Update for Winrevair Based on Phase 3 HYPERION Trial Data - https://www.drugtopics.com/view/fda-approves-update-for-winrevair-based-on-phase-3-hyperion-trial-data

FDA updates PAH label with trial data - 76% reduction in clinical worsening - https://news.mdspire.com/pulmonary/articles/fda-updates-pah-label-with-trial-data/

Roivant Announces Positive Results from PHocus Study of Mosliciguat in PH-ILD - 56.3% PVR reduction - https://www.biospace.com/press-releases/roivant-announces-positive-results-from-phocus-study-of-mosliciguat-in-patients-with-pulmonary-hypertension-associated-with-interstitial-lung-disease-ph-ild-and-unveils-ongoing-phase-3-phrontier-study