Topline Sotatercept Results Positive Treating Pulmonary Arterial Hypertension
JUNE 26, 2020
David Badesch, MD
Investigators presented data showing the drug resulted in a statistically significant reduction in pulmonary vascular resistance when compared to placebo, the primary endpoint of the 24 week trial.
The data was presented virtually at the American Thoracic Society (ATS) 2020 Virtual Sessions this week by investigator David Badesch, MD, Professor of Medicine and Clinical Director of the Pulmonary Hypertension Center at the University of Colorado.
The phase 2 double-blind, placebo-controlled study included 106 patients who were randomized to receive either 0.3 mg/kg of sotatercept, 0.7 mg/kg of sotatercept subcutaneously every 21 days in combination with stable background PAH-specific therapies, including mono, double, and triple therapies, or a placebo.
Of the 106 patients in the trial, 35% were receiving double background PAH-specific therapies, while 56% were receiving triple background PAH-specific therapies.
The investigators achieved the primary endpoint of the study, as well as key secondary endpoints, showing concordance of results across multiple additional endpoints, regardless of baseline characteristics.
The team also achieved the protocol-defined improvement in the key secondary endpoint of the six-minute walk distance (6MWD) test at 24 weeks.
Both dosage groups of the study drug achieved at least a 50-meter increase from baseline, which was demonstrated in the 0.3 mg/kg group (58 meters) and the 0.7 mg/kg group (50 meters). This allowed for a pre-specified pooled analysis.
Overall, patients treated with sotatercept achieved a 54-meter change from baseline, as well as a placebo-corrected difference of 25 meters (nominal P = 0.03).
The investigators also found improvement across multiple exploratory study endpoints at week 24, including a 51% reduction in amino-terminal brain natriuretic proceptide (NT-proBNP), as well as a 20% reduction in mean pulmonary arterial pressure.
In addition, 23% of participants improved their World Health Organization (WHO) functional class.
The study drug was generally well-tolerated, with adverse events consistent with previously published data on sotatercept in clinical trials involving other patient populations.
Serious treatment-emergent adverse events were found in 2 patients (6%) receiving 0.3 mg/kg of the study drug with background therapy, 10 participants (24%) receiving 0.7 mg/kg of sotatercept with background therapy, and 3 individuals (9%) receiving placebo plus background therapy.
Hemoglobin increases was found in 1 patients (3%) in the lower sotatercept dose group and 6 patients (14%) in the higher dose group.
The investigators also found 2 patients (6%) in the 0.3 mg/kg sotatercept dose group and 5 patients (12%) in the 0.7 mg/kg sotatercept dose group experienced thrombocytopenia.
The treatment-emergent adverse events found in at least 10% of all patients included headache, diarrhea, peripheral edema, dizziness, fatigue, hypokalemia, and nausea.
As of June 22, 2020, 94 of 97 patients who opted to participate in the 18-month extension period of the trial were still enrolled; 64 patients have now been treated with sotatercept for at least 12 months.
“These results, seen on top of existing therapies in heavily pretreated patients, are consistent with sotatercept exerting its effects through a mechanism distinct from currently approved agents,” Badesch said in a statement. “By selectively binding ligands of the TGF-beta superfamily, sotatercept is designed to rebalance key signaling pathways whose disruption has been shown to be important in PAH biology. If sotatercept’s efficacy and safety are confirmed in the next phase of clinical development, I believe it has the potential to substantially alter the way we treat patients with PAH.”