Sotatercept improved six-minute walk distance by 40.8 meters at week 24 versus placebo in adults with pulmonary arterial hypertension on background therapy.- Merck Inc.
Merck Inc., known as MSD outside of the United States and Canada, announced full results from the Phase III STELLAR trial, which evaluated sotatercept, Merck’s novel investigational activin signaling inhibitor biologic, in combination with stable background therapy for the treatment of adult patients with pulmonary arterial hypertension (PAH) (WHO Group 1). Sotatercept significantly improved exercise capacity, increasing 6-minute walk distance (6MWD) by 40.8 meters (95% CI, 27.5-54.1; p<0.001) from baseline at week 24, the study’s primary endpoint.></0.001)>
In addition, sotatercept demonstrated statistically significant and clinically meaningful improvements in eight of nine secondary outcome measures, including improvements in WHO functional class (WHO FC) and pulmonary vascular resistance (PVR). Sotatercept reduced the risk of clinical worsening or death by 84% compared to placebo with a median follow-up of 32.7 weeks (HR=0.16 [95% CI, 0.08-0.35]; p<0.001). the safety profile of sotatercept was generally consistent with that observed in previous studies with sotatercept. these data were presented today at the american college of cardiology’s 72nd annual scientific session together with world heart federation’s world congress of cardiology and simultaneously published in the new england journal of medicine.></0.001).>
“PAH is a rare, rapidly progressive, debilitating and ultimately life-threatening condition with a five-year mortality rate of 43 percent,” said Dr. Marius Hoeper, Hannover Medical School, Germany, and lead investigator. “Sotatercept demonstrated profound improvements across the primary endpoint of six-minute walk distance and multiple secondary endpoints, including improvements in WHO functional class and pulmonary vascular resistance. These landmark results show the potential of sotatercept and the approach of targeting cellular signaling associated with vascular hyperproliferation and pathological remodeling for the treatment of PAH.”
STELLAR is the first Phase III study to evaluate the efficacy of an activin signaling inhibitor added to background therapy in adults with PAH.
Key findings from secondary endpoints included : i.The proportion of patients who achieved multicomponent improvement at week 24 (defined as improvement in 6MWD, improvement in N-terminal pro-B-type natriuretic peptide (NT-proBNP) level, and either improvement in WHO FC or maintenance of WHO FC II) was significantly greater with sotatercept versus placebo (38.9% [n=63/163] versus 10.1% [n=16/160]; p<0.001). ii. sotatercept demonstrated a statistically significant reduction of -234.6 dyn·sec·cm?5 (95% ci, -288.4 to -180.8; p><0.001) from baseline at week 24 in pvr – a calculation of pulmonary artery pressure, pulmonary artery wedge pressure and cardiac output – versus placebo. iii. sotatercept demonstrated a statistically significant reduction of -441.6 (95% ci, -573.5 to -309.6; p><0.001) from baseline at week 24 in nt-probnp levels versus placebo. iv. patients receiving sotatercept were significantly more likely to improve and maintain who fc at week 24 versus placebo. 29.4% (n="48/163)" of patients in the sotatercept group improved in who fc compared to 13.8% (n="22/160)" in the placebo group (p><0.001). v. sotatercept significantly reduced events associated with clinical worsening (defined by death of any cause or specified non-fatal clinical worsening events). with a median follow-up of 32.7 weeks, 9 of 163 patients in the sotatercept group died or experienced a clinical worsening event versus 42 of 160 patients in the placebo group (hr="0.16" [95% ci, 0.08 to 0.35]; p><0.001). vi.a significantly greater proportion of patients treated with sotatercept achieved or maintained a low french risk score (attaining or maintaining all three low-risk criteria: who functional class i or ii, 6-minute walk distance> 440 meters, and NT-proBNP level < 300 pg per milliliter) versus placebo (39.5% [n=64/163] versus 18.2% [n=29/160]; p<0.001). in patient-reported outcomes using the pah-sympact questionnaire, the average scores for physical impacts (change from baseline: -0.26 [95% ci, -0.49 to -0.04]; p="0.010)" and cardiopulmonary symptoms (change from baseline: -0.13 [95% ci, -0.26 to -0.01]; p="0.028)" were significantly reduced in patients treated with sotatercept versus placebo. pah-sympact® is a disease-specific patient-reported outcome instrument. domain scores range from 0 to 4 with higher scores indicating greater severity of symptoms. vii.the average score for cognitive emotional impacts using pah-sympact was not significantly different between patients treated with sotatercept versus placebo (p="0.156).">
Treatment-emergent adverse events (TEAEs) occurred in 90.8% of patients who received sotatercept versus 91.9% of patients who received placebo, while severe TEAEs were observed in 12.9% versus 18.1% of patients, respectively. Adverse events that occurred more frequently with sotatercept versus placebo were bleeding events, telangiectasia, increased hemoglobin levels, thrombocytopenia, increased blood pressure, and dizziness.
See- ORIGINAL ARTICLEMAR 06, 2023 "Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension" M.M. Hoeper and Others10.1056/NEJMoa2213558.
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