Adverse reactions ≥10% in patients receiving WINREVAIR^TM (sotatercept-csrk) and at least 5% more than placebo in STELLAR^a

Adverse reaction	WINREVAIR (n=163)	Placebo (n=160)
Headache	40 (24.5%)	28 (17.5%)
Epistaxis	36 (22.1%)	3 (1.9%)
Rash	33 (20.2%)	13 (8.1%)
Telangiectasia	27 (16.6%)	7 (4.4%)
Diarrhea	25 (15.3%)	16 (10.0%)
Dizziness	24 (14.7%)	10 (6.3%)
Erythema	22 (13.5%)	5 (3.1%)

The median duration of treatment was 273 days in the placebo group and 313 days in the WINREVAIR group.

^aDouble-blind placebo-controlled period + long-term double-blind period of STELLAR.

WINREVAIR Had a Low Rate of Discontinuation Due To Adverse Reactions: 4% On WINREVAIR vs 7% On Placebo

Long-term safety data for WINREVAIR were generally similar to STELLAR data

Pooled long-term safety data are available from 431 patients who participated in multicenter phase 2 (PULSAR, SPECTRA) and phase 3 (STELLAR) clinical trials. A majority of these patients continued in SOTERIA, an ongoing, open-label follow-up study of the long-term safety and efficacy of WINREVAIR.
The safety profile with long-term exposure was generally similar to that observed in the STELLAR study. The mean duration of exposure to WINREVAIR was 173 weeks with a maximum exposure of 335 weeks.
Intrapulmonary Right-to-Left Shunting: Cases of intrapulmonary right-to-left shunting have been reported in a clinical trial with WINREVAIR. In SOTERIA, right-to-left intrapulmonary shunting has been reported in 3 participants (<0.7%) who developed worsening hypoxemia despite improved PAH hemodynamics. Post-marketing cases have also been reported. 
Partial to complete improvement in oxygenation has been observed following discontinuation of WINREVAIR.

Additional Adverse Reactions from Phase 3 Clinical Trials

The following adverse reactions were reported in at least one adult patient receiving treatment with WINREVAIR. These adverse reactions are presented by system organ class and are ranked by frequency.

Skin and Subcutaneous Tissue Disorders:

1% and less than 10%: skin hypopigmentation

Gastrointestinal Disorders:

1% and less than 10%: gastrointestinal tract bleeding (including gastrointestinal hemorrhage, upper gastrointestinal hemorrhage, hematemesis, lower gastrointestinal hemorrhage, hematochezia, rectal hemorrhage, melaena, gastritis hemorrhagic), colonic angioectasia

WINREVAIR is a PAH treatment with a demonstrated tolerability profile on top of a broad range of background therapies

Report exposure during pregnancy or lactation to the Merck Sharp & Dohme LLC Adverse Event reporting line at 1-877-888-4231

Indication

WINREVAIR is an activin signaling inhibitor indicated for the treatment of adults with pulmonary arterial hypertension (PAH, Group 1 pulmonary hypertension) to improve exercise capacity and World Health Organization (WHO) functional class (FC), and reduce the risk of clinical worsening events including hospitalization for PAH, lung transplantation and death.

Selected Safety Information

Erythrocytosis: WINREVAIR may increase hemoglobin (Hgb). Severe erythrocytosis may increase the risk of thromboembolic events or hyperviscosity syndrome. Monitor Hgb before each dose for the first 5 doses, or longer if values are unstable, and periodically thereafter, to determine if dose adjustments are required.

Severe Thrombocytopenia: WINREVAIR may decrease platelet count. Severe thrombocytopenia may increase the risk of bleeding. Thrombocytopenia occurred more frequently in patients also receiving prostacyclin infusion. Do not initiate treatment if platelet count is <50,000/mm³. Monitor platelets 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: In clinical studies, serious bleeding (e.g., gastrointestinal, intracranial hemorrhage) was reported in 4% vs 1% (STELLAR) and 7% vs 5% (ZENITH) of patients taking WINREVAIR vs placebo, respectively. Patients with serious bleeding were more likely to be on prostacyclin background therapy and/or antithrombotic agents, or have low platelet counts. Advise patients about signs and symptoms of blood loss. Do not administer WINREVAIR if the patient is experiencing serious bleeding.

Embryo-Fetal Toxicity: WINREVAIR may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with WINREVAIR and for at least 4 months after the final dose. Pregnancy testing is recommended for females of reproductive potential before starting WINREVAIR treatment.

Impaired Fertility: Based on findings in animals, WINREVAIR may impair female and male fertility. Advise patients on the potential effects on fertility.

Adverse Reactions: The most common adverse reactions (≥10% for WINREVAIR and at least 5% more than placebo) occurring in the STELLAR phase 3 clinical trial were headache (24.5% vs 17.5%), epistaxis (22.1% vs 1.9%), rash (20.2% vs 8.1%), telangiectasia (16.6% vs 4.4%), diarrhea (15.3% vs 10.0%), dizziness (14.7% vs 6.3%), and erythema (13.5% vs 3.1%). The most common adverse reactions in the ZENITH trial were infections (67.4% vs 44.2%), epistaxis (45.3% vs 9.3%), diarrhea (25.6% vs 17.4%), telangiectasia (25.6% vs 3.5%), increased hemoglobin (15.1% vs 1.2%), rash (10.5% vs 4.7%), erythema (10.5% vs 3.5%), and gingival bleeding (10.5% vs 2.3%).

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with WINREVAIR, and for 4 months after the final dose.

Before prescribing WINREVAIR, please read the accompanying Prescribing Information. The Patient Information and Instructions for Use (1-vial kit, 2-vial kit) also are available.

Indication Indication

Selected Safety Information Selected Safety Information