New pulmonary hypertension drugs are competing for approval

MSD's Winrevair (sotatercept) and Janssen Korea's Opsynvi Tab (macitentan-tadalafil) win nod

Competition among pharmaceutical companies intensifies amid increasing treatment options…growing presence in clinical practices

Global pharmaceutical companies are introducing new treatment options for pulmonary hypertension, utilizing novel mechanisms, which are being successively approved in the Korean market.

 

These drugs are expected to change the clinical treatment paradigm.

 

It's anticipated that they will establish a new market alongside the currently reimbursed treatments.

 

According to the pharmaceutical industry source on July 28, the Ministry of Food and Drug Safety (MFDS) recently approved Winrevair (sotatercept) from MSD Korea and Opsynvi Tab (macitentan-tadalafil) from Janssen Korea as treatments for pulmonary hypertension.

 

Pulmonary hypertension is a rare, severe, intractable disease where the walls of the pulmonary arterioles abnormally thicken and narrow, causing pressure to rise.

 

As the disease progresses, symptoms like shortness of breath, chest pain, and fainting appear, severely limiting all aspects of daily life.

 

Additionally, the increased pressure in the right ventricle due to the narrowed pulmonary arteries gradually weakens the function of the right side of the heart, leading to a high risk of sudden death.

 

First, MSD Korea's Winrevair is an 'Activin Signaling Inhibitor (ASI), the first-in-class (as of July 2025)' to be approved in the field of pulmonary hypertension.

 

It is a new treatment mechanism that has emerged after 20 years.

 

Its mechanism directly addresses the fundamental cause of the disease by blocking the excessive proliferative signals of the protein complex 'activin,' which causes cell proliferation within pulmonary artery blood vessels, and by restoring the balance with anti-proliferative signals that inhibit cell growth, thereby inducing reverse remodeling to normalize the deformed vascular structure.

 

MFDS approved Winrevair for use in combination with existing treatments to improve the exercise capacity of adult patients (18 years or older) with pulmonary hypertension (WHO Group I) who are in WHO Functional Class II-III.

 

The three existing treatments are endothelin receptor antagonists (ERA), PDE-5 inhibitors (PDE-5i), and prostacyclin analogues (PCA).

 

With the addition of this new mechanism, the Activin Signaling Inhibitor, which differs from existing treatments, has further broadened the options for pulmonary hypertension patients.

 

The STELLAR clinical trial, which served as the basis for approval, evaluated the efficacy and safety of Winrevair in 323 adult patients with pulmonary hypertension in WHO-FC II or III.

 

During the 24-week study period, patients received either Winrevair or a placebo in combination with their existing treatment once every three weeks.

 

Winrevair increased the 6-minute walk distance by 40.8m compared to placebo at the 24-week mark (95% CI, 27.5-54.1; P<0.001) and reduced the risk of clinical worsening or death by 84% (HR 0.16, 95% CI, 0.08-0.35).

 

It also confirmed significant improvements compared to the placebo in eight secondary efficacy endpoints, including the WHO-FC, pulmonary vascular resistance (PVR), and the heart failure biomarker NT-proBNP levels.

 

Immediately after the approval of Winrevair, MFDS also approved Janssen Korea's oral pulmonary hypertension treatment, Opsynvi.

 

Specifically, MFDS approved Opsynvi for 'long-term treatment of adult patients with pulmonary hypertension (WHO Group I) who are in WHO Functional Class II-III.' This approval came one year after the U.S.

 

Food and Drug Administration (FDA) approved Opsynvi in March of last year.

 

Opsynvi is a combination of the PDE-5i Cialis and the ERA Adcirca, making it the first drug approved as a combination of these mechanisms.

 

PDE-5i has a mechanism that reduces pulmonary artery pressure, while ERA blocks the action of endothelin-1 (ET-1) to promote vasodilation.

 

The efficacy of Opsynvi was proven in the Phase 3 A DUE study.

 

The trial compared the efficacy and safety of the Opsynvi arm with the monotherapy arms of either Opsumit or Cialis.

 

After tracking patients for 24 months, Opsynvi reduced pulmonary vascular resistance (PVR), the primary endpoint, by up to 29% compared to the Cialis or Opsumit monotherapy arms.

 

As a result, more non-reimbursed but clinically available treatment options have become available in the domestic treatment market, following Bayer Korea's pulmonary hypertension treatment 'Adempas (riociguat),' which had been used on a non-reimbursed basis for 10 years until June.

 

For Winrevair, it has been recognized for its innovativeness and designated as the 24th drug under the MFDS Global Innovative Products on Fast Track (GIFT) in 2024.

 

It has also been selected as a target for the second concurrent approval-evaluation-negotiation pilot program, which may lead to rapid reimbursement.

 

Wook-Jin Chung, President of the Korean Pulmonary Hypertension Society (Professor of Cardiology at Gachon University Gil Medical Center), stated, "Pulmonary hypertension is a disease that makes even normal breathing difficult and is difficult to cure, causing physical and mental distress to patients." Chung added, "Winrevair, a new mechanism treatment that normalizes deformed pulmonary vascular structures, is also presented as an option that can be used in early treatment stages in updated global clinical guidelines based on the latest evidence.

 

This approval for patients with pulmonary hypertension in Korea has widened the range of treatment options."