Table 2.
Summary of Phase 2 and Phase 3 Randomized Placebo-controlled Clinical Trials of Sotatercept for the Treatment of PH
| Trial | Number of Patients | WHO Group | Risk Category | Background PAH Therapy | Target Dose | Endpoint | Trial Outcome | Adverse Events |
|---|---|---|---|---|---|---|---|---|
| PULSAR* | 106 | Group 1† | WHO-FC II and III with minimum PVR ⩾ 5 WU | Yes | 0.3 mg/kg SQ or 0.7 mg/kg; or placebo, q3 wk | Change in PVR at 24 wk | Least-squares mean difference of −239.5 dyn ⋅ s ⋅ cm−5 (2.9 WU); 95% CI = −329.3, −149.7; P < 0.001 | Thrombocytopenia, increased hemoglobin, SOTERIA* study; open-label long-term follow-up to assess safety |
| STELLAR‡ | 324 | Group 1† | WHO-FC II and III with minimum PVR ⩾ 5 WU | Yes | 0.7 mg/kg SQ; or placebo, q3 wk | Change in 6MWD at 24 wk | Hodges-Lehmann location shift of +40.8 m; 95% CI = 27.5, 54.1; P < 0.001 | Epistaxis, telangiectasis, thrombocytopenia, increased hemoglobin |
| HYPERION‡ | 662 | Group 1† with new diagnosis of PAH | WHO-FC II and III with minimum PVR ⩾ 4 WU and REVEAL Lite 2 risk score ⩾ 6 | Yes, clinically stable doses of a double combination of PAH therapies and diuretics | 0.7 mg/kg SQ; or placebo, q3 wk | Time to clinical worsening§ | Actively enrolling | — |
| ZENITH‡ | 200 | Group 1† with high risk of mortality | WHO-FC III or FC IV at high risk of mortality with REVEAL Lite 2 risk score ⩾ 9 | Yes, clinically stable on maximally tolerated double or triple-combination therapy | 0.7 mg/kg SQ; or placebo, q3 wk | Time to first confirmed morbidity or mortality event | Actively enrolling | — |
| CADENCE* | 150 | Combined pre- and postcapillary PH because of HFpEF | NYHA-FC II or III with PAWP > 15 mm Hg but <30 mm Hg | — | 0.3 or 0.7 mg/kg; or placebo, q3 wk | Change in PVR at 24 wk | Actively enrolling | — |
| MOONBEAM* | 42 | Group 1†ǁ PH in children ⩾1 to <18 yr old | — | Yes, clinically stable on maximally tolerated double or triple combination therapy | 0.3 mg/kg SQ, q3 wk | Serum trough of drug before next dose, % of participants with adverse events¶ | Actively enrolling | — |
Definition of abbreviations: 6MWD = 6-minute walk distance; CI = confidence interval; HFpEF = heart failure with preserved ejection fraction; NYHA-FC = New York Heart Association functional class; PAH = pulmonary arterial hypertension; PAWP = pulmonary arterial wedge pressure; PH = pulmonary hypertension; PVR = pulmonary vascular resistance; q3 wk = once every 3 weeks; RCT = randomized clinical trial; SQ = subcutaneous; WHO-FC = World Health Organization functional class; WU = Wood units.
Phase-2 randomized, double-blind, placebo-controlled RCT.
Idiopathic or heritable, connective tissue disease, or drug induced.
Phase-3 randomized, double-blind, placebo-controlled RCT.
Defined as time from randomization to the first confirmed morbidity event or death.
PAH-congenital heart disease with shunt closure >6 mo before screening and PAH with coincidental shunt.
No formal hypothesis, several primary endpoints, including these.