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Primary endpoint: 6-minute walk distance (6MWD)

In STELLAR, a 24-week study of adults with PAH (WHO FC II or III) on background therapy:

WINREVAIRTM (sotatercept-csrk) delivered a significant step forward for patients

Actor Portrayal

Patients taking WINREVAIR walked

41 meters moreᵃ (95% CI: 28: 54; P<0.001)

in 6 minutes at 24 weeks than patients on background therapy alone

Placebo-adjusted median increase from baseline in 6MWD

In a 24-week clinical study of adults with PAH (WHO Group 1, FC II or III) on stable background therapy, patients (N=323) were randomized 1:1 to WINREVAIR (n=163) or placebo (n=160) administered by subcutaneous injection once every 3 weeks.1

Change from baseline in 6MWD at week 24 in subgroups in STELLARa,b

WINREVAIR
(n=163)		Placebo
(n=160)		WINREVAIR vs placebo
Hodges-Lehmann location shift (95% CI)		WINREVAIR vs placebo
Hodges-Lehmann location
shift (asymptotic standard error) (95% CI)
Overall16316040.8 (6.79) (27.53, 54.14)
PAH diagnostic group
Idiopathic PAH8310651.3 (9.74) (32.17, 70.35)
Heritable PAH352425.6 (13.76) (-1.34, 52.61)
Drug/toxin-induced PAH7418.4 (16.78) (-14.51, 51.25)
CTD29198.7 (17.96) (-26.55, 43.86)
CHD with s/p shunt repair9792.4 (58.60) (-22.49, 207.26)
Background therapy
at baseline
Monotherapy946.3 (534.33) (-564.54, 1530.01)
Double565643.2 (11.32) (21.03, 65.42)
Triple9810043.5 (8.65) (26.51, 60.44)
Prostacyclin infusion
therapy at baseline
Yes656443.1 (10.45) (22.61, 63.59)
No989638.6 (8.88) (21.20, 56.00)
WHO FC
II797821.7 (7.68) (6.63, 36.72)
III848261.7 (10.64) (40.90, 82.59)
Baseline PVR
≤ 800 (dynes*sec/cm5)10810830.8 (7.77) (15.54, 45.98)
> 800 (dynes*sec/cm5)555261.6 (13.48) (35.23, 88.06)

Positive improvement trends were observed in prespecified subgroups, including double and triple therapy, and WHO FC II and III


These subgroup data were consistent with the primary endpoint

ᵃHodges-Lehmann location shift from placebo estimate (median of all paired differences).


ᵇChange from baseline in 6MWD at week 24 for subjects who died was imputed to -2000 meters to receive the worst rank. Change from baseline in 6MWD at week 24 for subjects who had missing data due to a non-fatal clinical worsening event was imputed to -1,000 meters to receive the next-worst rank.


CHD = congenital heart disease; CI = confidence interval; CTD = connective tissue diseases; PVR = pulmonary vascular resistance; s/p = systemic-to-pulmonary.

Reference:
1. Hoeper MM, Badesch DB, Ghofrani HA, et al; STELLAR Trial Investigators. Phase 3 trial of sotatercept for treatment of pulmonary arterial hypertension. N Engl J Med. 2023;388(16):1478-1490.

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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
Selected Safety Information

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.