A Study of Sotatercept in Participants With PAH WHO FC III or FC IV at High Risk of Mortality (MK-7962-006/ZENITH)

OS was defined as the time from randomization to death due to any cause. As pre-specified in the SAP, all deaths up to data cutoff, including among participants who completed or discontinued the study, were included except for those that occurred after enrollment in the long-term follow-up study (MK-7962-004) or after lung transplantation. The OS for participants, calculated using the non-parametric Kaplan-Meier method, is reported.

Transplant-free survival was defined as the time from randomization to the first lung transplantation or death due to any cause. As pre-specified in the SAP, all deaths up to data cutoff, including among participants who completed or discontinued the study, were included except for those that occurred after enrollment in the long-term follow-up study (MK-7962-004) or after lung transplantation. Transplant-free survival for participants, calculated using the non-parametric Kaplan-Meier method, is reported.

Mortality events were defined as death due to any cause throughout the study. As pre-specified in the SAP, all deaths up to data cutoff, including among participants who completed or discontinued the study, were included except for those that occurred after enrollment in the long-term follow-up study (MK-7962-004) or after lung transplantation. The percent of participants who experienced a mortality event is reported.

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: 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. Median change and full ranges are reported based on observed data.

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: 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 or intermediate REVEAL Lite 2.0 score at Week 24 is reported.

NT-proBNP is secreted by cardiomyocytes in response to ventricular stretch and is an established noninvasive marker of ventricular dysfunction in patients with PAH. Blood samples were collected at baseline and at Week 24 to measure NT-proBNP levels. Median change and full ranges are reported based on observed data.

mPAP is a hemodynamic variable associated with PAH severity and was measured measured at baseline and at Week 24 by right heart catheterization (RHC). Median change and full ranges are reported based on observed data.

PVR is a hemodynamic variable associated with PAH severity and was measured at baseline and at Week 24 by right heart catheterization (RHC). Median change and full ranges are reported based on observed data.

The severity of a participant's PAH symptoms was graded using the WHO FC system. WHO functional classification for PAH ranges 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). Participants who improve in WHO FC were classified into "Improved", "No change", or "Worsened" (Improved = reduction in FC; Worsened = increase in FC; No change = no change in FC). The percentage of participants who had improvement from baseline in WHO FC at the end of the treatment period is reported.

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 and full ranges are reported based on observed data.

CO is a prognostic hemodynamic parameter measured at baseline and at Week 24 by RHC. Median change and full ranges are reported based on observed data.

EQ-5D-5L is a standardized measure of health status, consisting of 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each assessed on a 5-point scale (1=no problem, 2=slight problems, 3=moderate problems, 4=severe problems, 5=extreme problems). Participants score each dimension based on their health that day and their responses are used to generate a health index score. Index scores could range from <0 (a health state equivalent to dead with negative values representing a state worse than dead) to 1 (full health). Higher scores indicated better health and a positive change in score indicated improved overall health. Per SAP, multiple imputation was used to impute missing data at Week 24 for reasons other than death or a non-fatal clinical worsening event. Range was based on the minimum and maximum of median scores across the imputed dataset (100 repetitions). The change from baseline to Week 24 in EQ-5D-5L index score is reported.