Merck (MSD outside the US and Canada) has shared encouraging phase 2 data for Winrevair (sotatercept-csrk) in a difficult cardiovascular condition, combined post- and precapillary pulmonary hypertension (CpcPH) caused by HFpEF.
This is an area with no approved therapies and poor patient outcomes, which makes the CADENCE results especially important.
Why CpcPH Matters
CpcPH sits inside Group 2 pulmonary hypertension, driven by left-heart disease and progressive vascular remodelling. Treating it is tough because patients face dual stressors:
- Left-sided heart dysfunction, which increases pressure backward into the lungs
- Pulmonary vascular changes, which worsen resistance and symptoms
- Limited treatment options, as no therapy is approved specifically for CpcPH
- Underdiagnosis, despite the condition’s severity
What the CADENCE Study Tested
CADENCE was a randomized, double-blind, placebo-controlled phase 2 study designed to test whether Winrevair could improve hemodynamics in adults with CpcPH due to HFpEF.
Key design elements included:
- Three arms: placebo, 0.3 mg/kg, and 0.7 mg/kg Winrevair
- Adults with HFpEF and NYHA class II or III symptoms
- 164 participants enrolled
- Endpoints spanning:
- Invasive hemodynamics
- Biomarkers
- Echocardiography
- Exercise capacity
The primary endpoint was change in pulmonary vascular resistance (PVR) at 24 weeks.
What Merck Reported
The drug met its main goal: a significant and clinically meaningful reduction in PVR versus placebo. This signals real pharmacological activity in a population that lacks established therapies.
Safety looked in line with Winrevair’s known profile, based on Merck’s preliminary assessment.
A key quote from Merck’s leadership highlighted the potential impact:
- Winrevair’s effect on PVR may translate into better outcomes for patients facing CpcPH due to HFpEF.
- CADENCE was built as a proof-of-concept study to guide phase 3 development.
What Happens Next
Merck plans to:
- Present full results at an upcoming scientific meeting
- Advance Winrevair into phase 3 trials for CpcPH due to HFpEF
This marks a major strategic step as Merck tests Winrevair beyond its current indication.
A Quick Look at Winrevair Today
Winrevair is already FDA-approved for adults with pulmonary arterial hypertension (PAH, WHO Group 1).
Its approved benefits include:
- Improved exercise capacity
- Better WHO functional class
- Lower risk of clinical worsening, hospitalization, lung transplant, or death
The drug works as an activin signaling inhibitor, shifting the balance between proliferative and anti-proliferative pathways in pulmonary vessels.
Preclinical data show:
- Thinner vessel walls
- Partial reversal of right ventricular remodelling
- Improved hemodynamics
Winrevair is also approved in more than 50 countries and is licensed from Bristol Myers Squibb.
Why This Matters for the Field?
If Winrevair succeeds in phase 3, it could become the first targeted therapy for CpcPH due to HFpEF. That would be a significant milestone for cardiology, pulmonology, and patients who currently have no dedicated treatment options.
