Sotatercept
A receptor-decoy protein that adds a new kind of treatment to pulmonary arterial hypertension
Sotatercept is a lab-made protein that soaks up activins and related growth signals before they reach their receptors. In pulmonary arterial hypertension, where the small lung arteries thicken and narrow, it was added to standard drugs and improved walking distance, blood-vessel pressures and the risk of getting worse. It is injected every three weeks, with blood counts checked because it raises haemoglobin and lowers platelets.
Manufacturer's recommended dosing (FDA label): 0.3 mg/kg, Once (first dose), Subcutaneous Details ↓
Recommended Dosing
Manufacturer's recommended dosing (FDA label)
From the prescribing information. Other doses studied, if any, are in the full dosing data below.
Work out syringe units → · New to syringes? · All dosing data ↓
What is it?
Pulmonary arterial hypertension (PAH) is a disease of the small arteries in the lungs. The cells in their walls multiply and the vessels remodel and narrow, so the right side of the heart has to pump against rising resistance, and long-term outcomes are poor. Sotatercept was built to act on that overgrowth rather than only on vessel tone, and in every trial it was added to the patient's existing PAH medicines.
It is a decoy receptor. The outer part of the human activin type IIA receptor is fused to the stem of an antibody, so the protein circulates and binds activins and growth differentiation factors, members of the TGF-beta family that push vessel cells to multiply. The idea, set out in the phase 2 trial, is to restore balance between growth-promoting signals and the growth-restraining bone morphogenetic protein pathway, which is faulty in many hereditary and idiopathic cases.
The trials were all add-ons to existing therapy. In PULSAR, a 24-week phase 2 trial, sotatercept cut pulmonary vascular resistance by roughly 146 to 240 units against placebo. In the phase 3 STELLAR trial of 323 patients in functional class II or III, walking distance improved by about 41 metres more than placebo at 24 weeks, along with resistance, NT-proBNP, functional class and time to clinical worsening. FDA approved it as Winrevair on March 26, 2024 (PMID 33789009; PMID 36877098).
Later trials looked at harder outcomes. ZENITH enrolled 172 patients at high risk of death on maximal background therapy and was stopped early: death, lung transplant or hospitalisation for PAH occurred in 17.4% on sotatercept against 54.7% on placebo. HYPERION, in 320 patients diagnosed within the past year, also stopped early, with clinical worsening in 10.6% against 36.9%. Deaths alone were not clearly different in HYPERION, and a meta-analysis of three randomised trials found no significant difference in all-cause mortality.
Its side effects were visible from the first trial: haemoglobin rises and platelets can fall. Nosebleeds and small dilated blood vessels in the skin (telangiectasia) were the commonest complaints in the phase 3 trials, and serious bleeding was more frequent than on placebo. The label asks for haemoglobin and platelet checks before each of the first five doses, and warns of possible harm to a fetus and to fertility.
Sotatercept is a specialist biologic for a diagnosed disease, tested only in people with pulmonary hypertension; none of its trials studied muscle or body composition. A heart-failure trial (CADENCE) suggests its vascular effects may extend to a form of pulmonary hypertension caused by left-heart disease, but that use is not approved.
Mechanism of Action
Sotatercept is a ligand trap. Its label calls it an activin signalling inhibitor: it binds activins and growth differentiation factors so they cannot activate cell-surface activin receptors.
Vessel wall remodelling
Trapping activins and GDFs is meant to rebalance growth-promoting and growth-inhibiting signalling in pulmonary vessels (PMID 33789009).
Pressure and the right ventricle
Lower pulmonary artery pressure and resistance and better right ventricular coupling followed treatment in STELLAR (PMID 37696565).
Red cells and platelets
Haemoglobin rises and platelets can fall, which is why the label requires counts before early doses (label, sections 2.3, 5.2, 5.3).
Published Research
The studies behind sotatercept, read from their PubMed abstracts. Every efficacy trial added it to existing PAH medicines; none tested it alone.
PULSAR: the phase 2 trial
In 106 adults on background PAH therapy, 24 weeks of sotatercept every 3 weeks lowered pulmonary vascular resistance by about 146 dyn·s·cm⁻⁵ at 0.3 mg/kg and 240 at 0.7 mg/kg against placebo, and lowered NT-proBNP; low platelets and raised haemoglobin were the commonest blood changes, and one patient died of cardiac arrest.
PULSAR extension
Of 106 PULSAR patients, 97 continued open-label; patients switched from placebo improved on every main measure, earlier responders kept their gains through 18 to 24 months, 30.8% had serious adverse events and three died of causes not judged drug-related.
STELLAR: the phase 3 trial
In 323 adults in functional class II or III on stable therapy, sotatercept (0.3 mg/kg rising to 0.7 mg/kg every 3 weeks) improved 6-minute walk distance by 40.8 m more than placebo at 24 weeks, plus eight of nine secondary end points; nosebleeds, dizziness, telangiectasia and higher haemoglobin were more frequent.
STELLAR: pressures and the right heart
In a post hoc analysis of STELLAR catheter and echo data, sotatercept lowered mean pulmonary artery pressure by about 14 mmHg and resistance by about 255 units against placebo, and improved right ventricular size and coupling, while cardiac output did not change.
SPECTRA: exercise testing
In a single-arm study of 21 class III patients completing 24 weeks, peak oxygen uptake rose by about 103 mL/min on invasive exercise testing, and cardiac MRI showed better right ventricular function.
ZENITH: patients at high risk of death
In 172 high-risk patients on maximal therapy, the trial stopped early: the composite of death, lung transplant or PAH hospitalisation occurred in 17.4% on sotatercept against 54.7% on placebo (hazard ratio 0.24); deaths were 8.1% against 15.1%.
HYPERION: within a year of diagnosis
In 320 recently diagnosed patients on two or three background drugs, clinical worsening occurred in 10.6% on sotatercept against 36.9% on placebo; deaths were 4.4% against 3.8%, and nosebleeds (31.9%) and telangiectasia (26.2%) were the commonest adverse events.
SOTERIA: longer-term safety
Among 426 patients followed for a mean of about 15 months, epistaxis (22.1%) and telangiectasia (16.9%) were the commonest events, 5.2% had serious bleeding, 3.5% stopped treatment, and earlier gains in walking distance and risk scores were largely kept at one year.
Meta-analysis of the randomised trials
Pooling three trials with 601 patients, sotatercept improved walking distance by about 41 m and functional class, and lowered resistance and pulmonary artery pressure, with no significant difference in all-cause mortality or NT-proBNP; epistaxis, raised haemoglobin and telangiectasia were more common.
Why 0.7 mg/kg
Exposure-response modelling across phase 1 to 3 studies found that walking distance, resistance and NT-proBNP improved with higher drug levels and levelled off around the exposure from 0.7 mg/kg every 3 weeks, while haemoglobin rises stayed manageable.
Reports after approval
In the FDA adverse event database for 2024, 613 reports named sotatercept as the main suspect; most signals matched the label, such as raised haemoglobin and telangiectasia, but cerebral haemorrhage and ascites emerged as unlabelled serious signals.
CADENCE: pulmonary hypertension from heart failure
In 164 patients with combined pre- and post-capillary pulmonary hypertension and preserved ejection fraction, sotatercept lowered pulmonary vascular resistance at 24 weeks against placebo at both doses; raised haemoglobin and diarrhoea were the commonest adverse events. Not an approved use.
Dosing Data
These are the Winrevair label's weight-based doses. Each dose depends on blood counts taken before it; the label sets the rules for delaying or restarting.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
What a Buyer Needs to Know
What is sold, how it is mixed, stored and taken, and what is known about its safety, quality and legal status. Each part names its source. Where we have none, it says unknown.
What is sold
Unknown: we hold no label and no published test that says what forms or vial sizes Sotatercept is sold in. A vial's own label is a seller's claim, not a source.
Mixing a vial: a worked example
The approved product Winrevair (sotatercept-csrk kit) is a powder that is mixed before use, with the liquid and volume its label names. Follow the label, not a general example. Its label says: “Patients and caregivers may administer WINREVAIR when considered appropriate and when they receive training and follow-up from the healthcare provider (HCP) on how to reconstitute, prepare, measure, and inject WINREVAIR.”
Source: Winrevair (sotatercept-csrk kit) label, sections 2 and 3 (DailyMed version 13, effective September 21, 2026).
Storage before and after mixing
Before mixing or first use: the label sentences we read do not say.
After mixing or first use: “Discard unused reconstituted solution.”
Source: Winrevair (sotatercept-csrk kit) label, sections 16 and 2 (DailyMed version 13, effective September 21, 2026).
How it is taken
As the approved label gives it: Subcutaneous (Once (first dose); Label: starting dose).
Source: Manufacturer's recommended dosing (FDA label): the route and frequency of each row in Dosing Data below.
What to expect, and when
How long it stays in the body: a half-life of about 24 days. After about five half-lives almost none is left.
How long the doses were given: Label: starting dose: Check haemoglobin and platelets first; Label: target dose: Long term; check counts before each of the first 5 doses; Label: restart after a delay over 9 weeks: Escalate once counts are acceptable.
When effects appear: unknown; no source on this page gives a time to effect for Sotatercept. Results reported in the studies are under Published Research.
Source: half-life: Winrevair (sotatercept-csrk) for injection US prescribing information (Merck Sharp & Dohme; DailyMed set 21693ee2, version 13, effective September 21, 2026; read October 28, 2026), section 12.3; Manufacturer's recommended dosing (FDA label), the duration of each row in Dosing Data below.
Side effects, and when to stop or get help
From the Side Effects section: Nosebleeds and telangiectasia (small dilated skin and mucosal vessels); Raised haemoglobin and low platelets; Serious bleeding more often than placebo; Dizziness, headache and diarrhoea; Post-marketing signals for cerebral haemorrhage and ascites. Full list and cautions ↓
When to stop or get help: unknown; the label's warnings summary we read gives no rule for stopping Sotatercept. Treat a severe or unexpected reaction as a reason to stop and see a doctor.
Source: the Side Effects section below (“From the studies above”).
Interactions
Unknown: a PubMed search for human interaction studies of Sotatercept (reviewed 2026-10-28) found none. Unknown is not the same as safe to combine.
Every peptide's record, with its source: the interaction matrix.
Checking what you bought
Unknown: no published independent test of Sotatercept products is in our lab-results database yet, so how products sold under this name measure up is not known.
To read a certificate of analysis, paste it into the COA decoder. Trust & Verification explains what independent testing can and cannot show.
Legal status
US: FDA Approved (FDA-approved March 26, 2024 as Winrevair (BLA761363). Sport: Prohibited at all times (S2.1.4).
Country by country ↓ · Regulatory tracker
Source: this entry's approval status and the WADA Prohibited List, as in Legal Status below.
Side Effects & Contraindications
Reported Side Effects
From the studies above.
Contraindications & Cautions
Contraindication and warnings from the Winrevair label (DailyMed set 21693ee2, version 13, effective September 21, 2026).
Legal Status
Sotatercept is an FDA-approved prescription biologic.
Frequently Asked Questions
?Is sotatercept a vasodilator?
It is not described as one. It traps growth signals linked to the overgrowth of the vessel wall, and in every trial it was added to the patient's existing PAH medicines.
?Does it help people live longer?
It lowered a combined outcome of death, transplant and hospitalisation in ZENITH and HYPERION, but deaths alone were not clearly different, and a meta-analysis found no significant mortality effect.
?Why are blood tests needed?
It raises haemoglobin and can lower platelets. The label asks for both before each of the first five doses and delays treatment if either crosses set limits.
?Is it related to myostatin or activin blockers sold for muscle?
It binds signals from the same family, but it was developed and tested only in pulmonary hypertension. None of the studies on this page measured muscle.
?How long does one dose last?
The label gives an effective half-life of about 24 days, with steady state after about 15 weeks of dosing every 3 weeks.
References
- [clinical-trial] Humbert M, et al. "Sotatercept for the Treatment of Pulmonary Arterial Hypertension." N Engl J Med, 2021;384(13):1204-1215. PMID: 33789009.
- [clinical-trial] Humbert M, et al. "Sotatercept for the treatment of pulmonary arterial hypertension: PULSAR open-label extension." Eur Respir J, 2023;61(1). PMID: 36041750.
- [clinical-trial] Hoeper MM, et al. "Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension." N Engl J Med, 2023;388(16):1478-1490. PMID: 36877098.
- [pubmed] Souza R, et al. "Effects of sotatercept on haemodynamics and right heart function: analysis of the STELLAR trial." Eur Respir J, 2023;62(3). PMID: 37696565.
- [clinical-trial] Waxman AB, et al. "SPECTRA Phase 2b Study: Impact of Sotatercept on Exercise Tolerance and Right Ventricular Function in Pulmonary Arterial Hypertension." Circ Heart Fail, 2024;17(5):e011227. PMID: 38572639.
- [clinical-trial] Humbert M, et al. "Sotatercept in Patients with Pulmonary Arterial Hypertension at High Risk for Death." N Engl J Med, 2025;392(20):1987-2000. PMID: 40167274.
- [clinical-trial] McLaughlin VV, et al. "Sotatercept for Pulmonary Arterial Hypertension within the First Year after Diagnosis." N Engl J Med, 2025;393(16):1599-1611. PMID: 41025556.
- [clinical-trial] Preston IR, et al. "A long-term follow-up study of sotatercept for treatment of pulmonary arterial hypertension: interim results of SOTERIA." Eur Respir J, 2025;66(1). PMID: 39978862.
- [review] Ershed M, et al. "Efficacy and safety of sotatercept in pulmonary arterial hypertension: a meta-analysis of randomized controlled trials." Expert Rev Respir Med, 2025;19(12):1273-1281. PMID: 40611681.
- [pubmed] Ait-Oudhia S, et al. "Population Pharmacokinetic/Pharmacodynamic and Exposure-Response Modeling Analyses of Sotatercept in Healthy Participants and Patients with Pulmonary Arterial Hypertension." Clin Pharmacol Ther, 2025;117(3):798-807. PMID: 39668469.
- [pubmed] Cao Z, et al. "Postmarketing analysis of sotatercept: identifying serious unlabelled events." Open Heart, 2025;12(2). PMID: 41033707.
- [clinical-trial] Gomberg-Maitland M, et al. "Sotatercept for Combined Post- and Precapillary Pulmonary Hypertension Associated With Heart Failure: Results From the Phase 2, Randomized, Placebo-Controlled CADENCE Study." Circulation, 2026;153(19):1446-1459. PMID: 41904795.
- [fda] Drugs@FDA (openFDA): BLA761363, WINREVAIR (sotatercept-csrk), Merck Sharp & Dohme; original approval March 26, 2024; marketing status Prescription. Read October 28, 2026.
- [fda-pi] Winrevair (sotatercept-csrk) for injection, US prescribing information, Merck Sharp & Dohme. DailyMed set 21693ee2, version 13, effective September 21, 2026; read October 28, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; doses, half-life and warnings from the Winrevair label on DailyMed (set 21693ee2, version 13, effective September 21, 2026), read October 28, 2026; approval from Drugs@FDA.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.