Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication WINREVAIR™ is 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 [see Clinical Studies (14.1) ] . FDA label
Also known as MK-7962, WINREVAIR™, ACE-011, ActRIIA-IgG1Fc
Sotatercept · 14 trials · 9 indications
TTCW was defined as time to first occurrence of any of the following events: cardiovascular (CV) death, hospitalization due to worsening heart failure (HF) or pulmonary hypertension (PH), urgent visits due to worsening HF or PH, or deterioration in exercise capacity (≥15% decrease from baseline in 6-minute walk distance \[6MWD\], confirmed by 2 tests) due to worsening HF or PH. CV deaths are defined as any deaths with a primary CV cause, including acute myocardial infarction (MI), sudden cardiac death, HF, PH worsening, stroke, and other CV causes.
PVR was the resistance against blood flow from the pulmonary artery to the left atrium. PVR was measured in dyn\*sec/cm\^5 by right heart catheterization (RHC). RHC was performed during the screening period (baseline) and Week 24. Per protocol, the change in PVR from baseline at Week 24 was reported for the primary treatment period.
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, the number of participants who experienced an AE were reported for the primary treatment period.
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Per protocol, the number of participants who discontinued study treatment due to AEs were reported for the primary treatment period.
Morbidity or mortality events were defined as all-cause death, lung transplantation, or PAH worsening-related hospitalization of ≥24 hours. All events were adjudicated by a blinded, independent committee of clinical experts. Only adjudication-confirmed lung transplantation and PAH worsening-related hospitalization of ≥24 hours were included in the primary analysis. All deaths that are a first event for a participant were included regardless of adjudication. The time from randomization to the first confirmed morbidity or mortality event, calculated using the non-parametric Kaplan-Meier method, is presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE will be reported.
ADAs will be detected in serum. The number of participants with detectable ADAs will be reported.
Blood samples will be collected to determine the concentration of platelets and hemoglobin.
Blood samples will be collected to determine the concentration of creatinine, total bilirubin, and ALT.
Change from baseline in body weight will be reported.
Change from baseline in systolic and diastolic blood pressure will be reported.
Change from baseline in ECG (12-lead) for the determination of Fridericia's corrected QT interval (QTcF) will be reported.
The 6MWD was the distance walked in 6 minutes as a measure of functional capacity. This was assessed using the 6-minute walk test (6MWT). Per protocol, change from baseline in 6MWD at Week 24 was reported for DBPC period.
An AE was any untoward medical occurrence in a study participant administered a study drug, which did not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it was considered related to the study drug. Per protocol, the number of participants who discontinued study treatment due to an AE were reported for DBPC period.
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The concentration of hemoglobin will be presented.
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The hematocrit will be presented.
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The RBC count will be presented.
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The reticulocyte count will be presented.
Hematological parameters will be investigated in blood samples from participants by means of clinical laboratory assays and evaluated by the investigator. The platelet count will be presented.
BP will be assessed while the participant was seated after a period of rest in a quiet setting with no distractions (eg, television and cell phones).
Neutralizing antibody analysis will be performed on blood samples for participants who are confirmed as antidrug antibody-positive. The number of participants with detectable neutralizing antibodies at any time during the study will be presented.
Serum samples collected predose will be used to determine serum trough concentration (Ctrough) of sotatercept.
The change from baseline in PVRI will be presented.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to an AE will be reported.
Steady-state Cavg of sotatercept will be reported.
An AE is a health problem that happens or worsens during a study. Number of participants who discontinue study treatment will be reported.
Blood samples will be collected at multiple time points to estimate the AUCss of Sotatercept.
Blood samples will be collected at Predose Day 1, Day 7, Day 14, and Predose Day 21 to estimate the AUC0-3 weeks of Sotatercept.
An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The percentage of participants with 1 or more AEs will be assessed.
An AE is any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The percentage of participants who discontinued the study drug due to an AE regardless of study completion status will be assessed.
ADA to Sotatercept will be assessed.
PVR, a hemodynamic variable of pulmonary circulation, was measured by right heart catheterization (RHC). Participants missing a value at baseline were excluded from the analysis. Participants missing a value at Week 24 (other than death or experienced a clinical worsening event), multiple imputation was used to impute missing data. Participants who died, the worst-rank score was assigned. Participants missing a value at Week 24 due to a clinical worsening event, the next-worst-rank score was used. The 'Full Range' is the minimum and maximum of the 100 medians from the 100 imputed datasets.
Each participant's VO2 max was measured by an invasive cardiopulmonary exercise test (iCPET) at baseline and at 24 weeks.
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and at 24 weeks.
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
Each participant's PVR, at resting supine, was measured by right heart catheterization at baseline and the timepoint at which the third right heart catheterization was performed, which occurred between Month 18 and Month 24.
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
An AE is any untoward medical occurrence in a study participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product.
The responder rate includes non-transfusion dependent efficacy (NTDE) participants and transfusion dependent efficacy (TDE) participants. For non-transfusion dependence efficacy (NTDE) participants who required \< 4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as an increase of \>=1.5 g/dL hemoglobin sustained for 56 days over a period of \>=8 weeks. For transfusion dependence efficacy (TDE) participants who required \>=4 units of RBCs in the 8 weeks prior to start of therapy, HI-E was defined as a decrease of \>= 4 units of RBCs transfused sustained for 56 days over a period of 8 weeks.
| Arm | Type | Description |
|---|---|---|
| Sotatercept | EXPERIMENTAL | Participants will receive sotatercept via subcutaneous (SC) injection every 3 weeks at an initial dose of 0.3 mg/kg until end of study (up to approximately 37 months). |
| Placebo | PLACEBO_COMPARATOR | Participants will receive matching placebo via SC injection every 3 weeks until end of study (up to approximately 37 months). |
| Sotatercept plus background PAH therapy | EXPERIMENTAL | Sotatercept at a starting dose of 0.3 mg/kg with a target dose of 0.7 mg/kg administered subcutaneously (SC) every 21 days plus background PAH therapy |
| Placebo plus background PAH therapy | PLACEBO_COMPARATOR | Placebo administered (SC) every 21 days plus background PAH therapy |
| Weight-banded sotatercept dosing | EXPERIMENTAL | Participants will receive sotatercept via subcutaneous (SC) injection every 3 weeks at an initial dose of up to 45 mg and then at a maintenance dose of up to 90 mg using a weight-banded method and will continue treatment for up to 24 months. All eligible participants will receive weight-banded dosing at the dosing level (initial or maintenance) at which they finished MK-7962-024 (LIGHTRAY). Participants will continue to take their background PAH therapy during the study. |
| Sotatercept 0.3 mg/kg | EXPERIMENTAL | Participants receive sotatercept 0.3 mg/kg subcutaneous (SC) injection every 3 weeks (Q3W) for up to approximately 10 years or until discontinuation. |
| Sotatercept 0.7 mg/kg | EXPERIMENTAL | Participants receive sotatercept 0.7 mg/kg SC injection Q3W for up to approximately 10 years or until discontinuation. |
| Weight-based sotatercept dosing | EXPERIMENTAL | Participants will receive sotatercept via subcutaneous (SC) injection every 3 weeks at an initial dose of 0.3 mg/kg and then at a maintenance dose of 0.7 mg/kg using a weight-based method during a 24-week treatment period. Participants will continue to take their background PAH therapy during the study. |
| Children ≥1 to <18 years old | EXPERIMENTAL | Participants will receive a subcutaneous (SC) injection every 3 weeks (Q3W) of 0.3 mg/kg. Dosage may be adjusted based on protocol-specific guidelines. |
| Sotatercept 0.3 mg/kg, escalating to 0.7 mg.kg | EXPERIMENTAL | Sotatercept SC at a starting dose level of 0.3 mg/kg for 3 dosing visits (Q3W), then escalating to 0.7 mg/kg SC on the fourth dosing visit and Q3W for the remainder of the 24-week treatment Period. |
| Sotatercept 0.1 mg/kg | EXPERIMENTAL | Sotatercept 0.1 mg/kg |
| Sotatercept 0.5 mg/kg | EXPERIMENTAL | Sotatercept 0.5 mg/kg |
| Sotatercept 1.0 mg/kg | EXPERIMENTAL | Sotatercept 1.0 mg/kg |
| Sotatercept 1.5 mg/kg | EXPERIMENTAL | Sotatercept 1.5 mg/kg |
| Sotatercept 2.0 mg/kg | EXPERIMENTAL | Sotatercept 2.0 mg/kg |
| Name | Type | Description |
|---|---|---|
| Sotatercept | BIOLOGICAL | SC injection administered every 3 weeks. |
| Placebo | BIOLOGICAL | SC injection administered every 3 weeks. |
| Background PAH Therapy | DRUG | Background PAH therapy may consist of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist. |
| Sotatercept 0.3 mg/kg | DRUG | Administered by subcutaneous injection. Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1. |
| Sotatercept 0.3 mg/kg escalating to 0.7 mg/kg | DRUG | Administered by subcutaneous injection. Sotatercept (ACE-011) is a recombinant fusion protein consisting of the extracellular domain of the human activin receptor type IIA linked to the Fc piece of human IgG1. |
| SOC | OTHER | SOC therapy refers to combination therapy consisting of drugs from two or more of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5 (PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist. |
Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has clinical diagnosis of HF with preserved ejection fraction on optimized guideline-directed medical therapy * Has CpcPH confirmed by right-heart catheterization * Has NYHA FC II or III Exclusion Crit...
Top 13 of 15 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 8 | PHASE3 | Sotatercept, Riociguat, Frespaciguat |
| United Therapeutics Corporation | UTHR | 5 | PHASE3 | Ralinepag, Tyvaso (treprostinil) |
| Insmed Incorporated | INSM | 4 | PHASE3 | Treprostinil Palmitil |
| Johnson & Johnson | JNJ | 4 | PHASE3 | selexipag, Macitentan |
| Liquidia Corporation | LQDA | 4 | PHASE3 | L606, LIQ861 Treprostinil, LIQ861 |
| Tenax Therapeutics, Inc. | TENX | 3 | PHASE3 | Levosimendan (TNX-103) |
| Inhibikase Therapeutics, Inc. | IKT | 2 | PHASE3 | IKT-001 |
| Roivant Sciences Ltd. | ROIV | 3 | PHASE3 | Mosliciguat |
| Regeneron Pharmaceuticals, Inc. | REGN | 1 | PHASE2 | REGN13335 |
| Tectonic Therapeutic Inc | TECX | 2 | PHASE2 | TX45 |
| Gossamer Bio, Inc. | GOSS | 1 | PHASE3 | Seralutinib |
| Pfizer Inc. | PFE | 1 | PHASE2 | PF-07868489 |
| GSK plc Sponsored ADR | GSK | 2 | PHASE1 | HS235 |
Sotatercept is being studied for pulmonary arterial hypertension, pulmonary hypertension, and anemia. It is an investigational therapy in clinical development and is not described as approved. Development covers adult and pediatric populations, including a Phase 3 study in combined postcapillary and precapillary pulmonary hypertension with heart failure with preserved ejection fraction.
Sotatercept targets INHBA and acts as an inhibitor. INHBA is part of the activin signaling pathway, and inhibiting this target is the mechanism under study in the conditions being evaluated. The program is listed with a small molecule modality.
Sotatercept is developed by Merck & Company, Inc., which trades under the ticker MRK. The company is running the clinical program, including studies labeled MK-7962, across pulmonary hypertension and anemia indications.
Sotatercept is in Phase 2 development overall, with individual trials spanning Phase 2 and Phase 3. Ten trials are listed in total: four active and six completed, with 1,827 participants enrolled across the program. It is investigational and not described as approved.
Sotatercept trials include NCT07839585, a Phase 3 study in combined postcapillary and precapillary pulmonary hypertension with heart failure with preserved ejection fraction; NCT07646860, a Phase 2 study in Japanese children with pulmonary arterial hypertension; NCT07218029, a Phase 3 study in pulmonary arterial hypertension; and NCT06925750, the Phase 2 LIGHTRAY extension study.