Winrevair From Merck

The FDA has approved sotatercept-csrk subcutaneous injection (Winrevair) from Merck for the treatment of adults with pulmonary arterial hypertension (PAH, World Health Organization [WHO] Group 1) to increase exercise capacity, improve WHO functional class, and reduce the risk of clinical worsening events.1 PAH is a progressive and rare disease characterized by narrowed and thickened blood vessels in the lungs, resulting in strain on the heart and symptoms such as fatigue and shortness of breath. The condition is associated with high morbidity and mortality.²

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PHARMACOLOGY AND PHARMACOKINETICS

Sotatercept-csrk is an activin-signaling inhibitor that binds to activin A and other TGF-β superfamily ligands, which improves the balance between antiproliferative and proproliferative signaling to modulate vascular proliferation. This can reduce inflammation and inhibit proliferation of endothelial and smooth muscle cells in diseased vasculature and is associated with thinner vessel walls, partial reversal of right ventricular remodeling, and improved hemodynamics. Sotatercept-csrk reaches peak plasma concentration approximately 7 days after administration and steady state after approximately 15 weeks. It displays an elimination half-life of approximately 24 days.¹

DOSAGE AND ADMINISTRATION

Sotatercept-csrk is administered subcutaneously every 3 weeks. The recommended starting dose is 0.3 mg/kg and the target dose is 0.7 mg/kg. Hemoglobin and platelet count should be obtained before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter. Treatment should not be initiated if the platelet count is less than 50,000/mm3. Dose modifications may be required if increased hemoglobin or decreased platelets occur.¹

CLINICAL TRIALS

The efficacy of sotatercept-csrk was evaluated in the phase 3 STELLAR trial (NCT04576988), a double-blind, global, multicenter, parallel-group, placebo-controlled clinical trial of adults with PAH (WHO Group 1 functional class 2 or 3). Participants were randomly assigned 1:1 to receive either sotatercept-csrk (target dose 0.7 mg/kg) or placebo subcutaneously once every 3 weeks. Most participants were concomitantly using background medication for PAH, with 61% of participants using 3 agents, 35% using 2 agents, and 40% receiving prostacyclin infusions.

The study met its primary efficacy end point, which was change in 6-minute walk distance from baseline to week 24, with the sotatercept-csrk group increasing by 41 m. Treatment with sotatercept-csrk also demonstrated significant improvements at week 24 for multiple secondary outcomes. An improvement in functional class was demonstrated in 29% of participants in the sotatercept-csrk group vs 14% of those using placebo. Sotatercept-csrk reduced the risk of death from any cause or PAH clinical worsening events by 84% as compared with placebo. The sotatercept-csrk group also demonstrated an improvement from baseline in pulmonary vascular resistance and N-terminal pro-B-type natriuretic peptide levels^.1,2

CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS

There are no contraindications to treatment with sotatercept-csrk.

Sotatercept-csrk may increase hemoglobin and decrease platelet counts. Severe erythrocytosis may increase the risk of hyperviscosity syndrome and thromboembolic events, and severe thrombocytopenia may increase the risk of bleeding. Hemoglobin and platelets should be monitored before each dose for the first 5 doses or longer if values are unstable, and periodically thereafter to determine whether dose adjustments are required. Serious bleeding events have been reported and are more likely to occur with concomitant use of antithrombotic medications and/or prostacyclin or in patients with low platelet counts.

Because sotatercept-csrk may cause fetal harm when taken during pregnancy, women of reproductive age should be advised of the potential risk to a fetus and counseled to use effective contraception during treatment and for 4 months after stopping the medication. Sotatercept-csrk should not be used during breastfeeding. The medication may impair female and male fertility.

The most common adverse reactions are diarrhea, dizziness, epistaxis, erythema, headache, rash, and telangiectasia.¹

REFERENCES

1. Winrevair. Prescribing information. Merck & Co, Inc; 2024. Accessed May 3, 2024. https://www.merck.com/product/usa/pi_circulars/w/winrevair/winrevair_pi.pdf

2. FDA approves Merck’s Winrevair (sotatercept-csrk), a first-in-class treatment for adults with pulmonary arterial hypertension (PAH, WHO*Group 1). News release. Merck. March 26, 2024. Accessed May 3, 2024. https://www.merck.com/news/fda-approves-mercks-winrevair-sotatercept-csrk-a-first-in-class-treatment-for-adults-with-pulmonary-arterial-hypertension-pah-who-group-1/