Trial Outcomes & Findings for Study of Sotatercept in Newly Diagnosed Intermediate- and High-Risk PAH Participants (MK-7962-005/A011-13) (NCT NCT04811092)

Of the 321 participants who were randomized, one participant was randomized but withdrew from study before receiving study intervention. This participant, who was randomized to the sotatercept group, had no data collected for study specific baseline characteristics or outcome measures and was excluded from all analysis populations.

The analysis population only included participants who started study intervention.

Time to clinical worsening (TTCW) is defined as time from randomization to the first confirmed morbidity event or death. Clinical worsening events are defined as all-cause death, non-planned PAH-related hospitalization of ≥ 24 hours in duration, atrial septostomy, lung transplant, and/or deterioration in performance in 6-minute walk test from baseline combined with one of the following conditions: worsening of WHO FC from baseline, signs/symptoms of increased right heart failure, addition of a background PAH therapy or change in the background PAH therapy delivery route to parenteral. All events were adjudicated by a blinded, independent committee of clinical experts. The median TTCW is presented.

The multicomponent improvement outcome measure is determined by the percentage of participants achieving all of the following at Week 24 relative to baseline: * Improvement in 6MWD (increase ≥30 m) * Improvement or maintenance/achievement of NT-proBNP (decrease in NT-proBNP ≥30%) or maintenance/achievement of NT-proBNP level \<300 ng/L * Improvement in WHO FC or maintenance of WHO FC II (indicated by maintaining the same WHO FC or a lower WHO FC by Week 24 relative to baseline) The percentage of participants achieving the multicomponent improvement endpoint is presented.

REVEAL Lite 2.0 risk scoring is used to guide PAH treatment decisions. Total score uses 6 variables with each assessed based on contribution to mortality risk. Variables and sub-score ranges: estimated glomerular filtration rate \[eGFR\] (0, +1), WHO FC (-1, 0, +1, +2), SBP (0, +1), heart rate (0, +1), 6MWD (-2, -1, 0, +1), and NT-proBNP (-2, 0, +2). Sub-scores are added to a base score of +6 and a total score of 1 to 14 is obtained (≤5=low risk; 6,7=intermediate risk; ≥8=high risk). A higher score = higher risk. Per SAP, participants who did not have a REVEAL risk score at Week 24 were considered as non-responders and multiple imputation was not conducted for this endpoint. Comparisons between this analysis reporting non-imputed data should not be made to other REVEAL analyses which included imputation of missing Week 24 data. The percentage of participants who achieved a low REVEAL Lite 2.0 score at Week 24 is reported.

The simplified French Risk Score uses WHO FC, 6MWD, and NT-proBNP to determine the total risk score. A low risk score can be defined as attaining or maintaining all three low-risk criteria: WHO FC I or II, 6MWD \> 440m, and NT-proBNP \< 300 ng/L. The percentage of participants who maintain or achieve a low risk score at Week 24 versus baseline using the simplified French Risk score calculator is presented.

NT-proBNP is a circulating biomarker that reflects myocardial stretch and is an established biomarker used to determine the ventricular dysfunction in participants with PAH. NT-proBNP was measured at Day 1 (baseline) and at Week 24. The median change from baseline in NT-proBNP at Week 24 is presented.

The severity of an individual's PAH symptoms was graded using the WHO FC system. WHO functional classification for PAH range from Class I (no limitation in physical activity, no dyspnea with normal activity), Class II (slight limitation of physical activity), Class III (marked limitation of physical activity) and Class IV (cannot perform a physical activity without any symptoms, dyspnea at rest). The change from baseline in WHO FC is classified into "Improved", "No change" and "Worsened". Improvement = reduction in FC, worsened = increase in FC and no change = no change in FC. The percentage of participants who improve in WHO FC or maintain WHO FC II at 24 Weeks from Baseline is presented.

The 6-minute walk distance (6MWD) was measured using the 6-Minute Walk Test (6MWT). The 6MWT measures the distance covered in 6 minutes and is intended to measure changes in functional exercise capacity. Each participant's 6MWD was measured at baseline and at 24 weeks. An increase in the distance walked during the 6MWT indicated improvement in functional exercise capacity. Median change from baseline in 6MWD at Week 24 is reported.

Overall survival is defined as the time from randomization to date of death due to any cause. OS is presented.

The PAH SYMPACT is a 23-item questionnaire to measure pulmonary arterial hypertension (PAH)-related symptoms and impact of PAH on daily life. The physical impact domain consists of walking slowly on a flat surface, walking quickly on a flat surface, walking uphill, carrying things, doing light indoor household chores, washing, or dressing oneself, and needing help from others. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (not difficult at all) to 4 (extremely difficult). A domain score was calculated by summing the individual responses for each item and dividing by the number of impact items (range: 0=no physical impact to 4=severe physical impact). A higher score indicated more severe physical impact. Mean change from baseline in responses in physical symptoms of the PAH-SYMPACT questionnaire at Week 24 is reported.

The PAH SYMPACT is a 23-item questionnaire to measure PAH-related symptoms and impact of PAH on daily life. The cardiopulmonary symptoms consist of shortness of breath, fatigue, lack of energy, swelling in the ankles or legs, swelling in the stomach area, and cough. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (no symptom at all) to 4 (very severe symptoms). The mean individual symptom item score was determined for each of the 6 items and a domain score was calculated by summing the mean individual symptom item scores and dividing by the number of items (range: 0=no cardiopulmonary symptoms to 4=severe cardiopulmonary symptoms). A higher score indicated more severe symptoms experienced. Mean change from baseline in cardiopulmonary symptoms of the PAH-SYMPACT questionnaire at Week 24 is reported.

The PAH SYMPACT is a 23-item questionnaire to measure PAH-related symptoms and impact of PAH on daily life. The Cognitive/Emotional Impact domain consists of thinking clearly, feeling sad, feeling worried, and feeling frustrated. Participants were asked to recall and report on each item experienced in past 7 days. Score for each item ranges from 0 (not difficult at all) to 4 (extremely difficult). A domain score was calculated by summing the individual responses for each item and dividing by the number of impact items (range: 0=no cognitive/emotional impact to 4=severe cognitive/emotional impact). A higher score indicated more severe cognitive/emotional impact. Mean change from baseline in responses in the Cognitive/Emotional Impacts Domain Score of the PAH-SYMPACT questionnaire at Week 24 is reported.

An AE is any untoward medical occurrence in a clinical investigation participant administered a study drug, which does 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 is considered related to the study drug. The percentage of participants who experienced an AE are presented.

An AE is any untoward medical occurrence in a clinical investigation participant administered a study drug, which does 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 is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE are presented.

Blood samples collected at designated timepoints were used to determine the ADA response to sotatercept. The number of participants who had ADAs to sotatercept over time is presented.