Winrevair (sotatercept-csrk) might become Merck’s next blockbuster after positive Phase 2 results from the CADENCE study showed it led to significant improvements in pulmonary blood flow in patients with precapillary pulmonary hypertension due to HFpEF.
- Heart failure with preserved ejection fraction (HFpEF) makes up more than 50% of the 6.7M U.S. HF cases, which is both a strain on the healthcare system and a pharmaceutical opportunity.
- Initially developed for PAH, Merck acquired Winrevair through its $11.5B Acceleron Pharma acquisition in 2021.
- The FDA has approved several HFpEF treatments but Winrevair is a new mechanism that targets activin protein signaling to regulate cell growth and division.
Focused on exploring Winrevair’s HF impact, the Phase 2 CADENCE study enrolled 164 adults with PAH caused by HFpEF, comparing two Winrevair doses against placebo over approximately six months and found that…
- Winrevair provided “significant and clinically meaningful” improvement to pulmonary blood flow at six months compared to placebo, meeting the study’s main goal.
- The trial also specifically targeted HFpEF patients with secondary pulmonary hypertension, a subset experiencing particularly severe symptoms and complications.
With FDA approval secured for PAH, Merck is aggressively pursuing HFpEF expansion as part of its strategic response to impending Keytruda patent expiration threatening half its pharmaceutical revenue.
- Winrevair generated $976M in sales over the first nine months of 2025 based solely on its PAH indication which suggests strong commercial traction and adoption.
- A big part of this rapid adoption stems from just how effective Winrevair is at treating PAH, with trials and real-world practice singing its praises alike.
The study is part of a larger HFpEF pharma trend, as Winrevair was not initially intended for HF, just like Bayer’s Kerendia (finerenone) which was originally a kidney drug.
- Both cases are indicative of just how devastating but lucrative HF is, since both the FDA and developers are quick to test drugs that don’t necessarily address the underlying mechanisms of HFpEF.
- That said, reducing symptoms and improving the patient’s overall quality of life following HF diagnosis are still solid reasons for earning an HF indication.
The Takeaway
Though only topline, Winrevair’s Phase 2 results bode well for Merck’s HF plans. We’ll have to wait and see if the full analysis and Phase 3 results back an FDA approval, but if they do, physicians will have yet another HF treatment in their toolkit, something that just ten years ago seemed like a distant possibility.
