Sotatercept effective for first-year use in PAH, industry study finds
Previous studies of sotatercept evaluated patients with pulmonary arterial hypertension (PAH) with a mean duration of eight years since diagnosis, so researchers looked at its use in patients who had received the diagnosis less than a year earlier.
Adding sotatercept to background therapy resulted in a lower risk of clinical symptom worsening than placebo in adults with pulmonary arterial hypertension (PAH) who had received the diagnosis less than a year before, an industry-funded study reported.
The trial included 320 adult group 1 PAH patients who had World Health Organization functional class II or III disease, had received the diagnosis less than a year earlier, had an intermediate or high risk of death, and were receiving double or triple background therapy
They were randomized to add-on therapy with subcutaneous sotatercept (at a starting dose of 0.3 mg/kg of body weight escalated to a target dose of 0.7 mg/kg every 21 days) or placebo. The study was funded and designed by Merck.
The primary end point was clinical worsening, defined as a composite of death from any cause, unplanned hospitalization lasting at least 24 hours for worsening of PAH, atrial septostomy, lung transplantation, or deterioration in performance in exercise testing due to PAH, assessed in a time-to-first-event analysis. The trial was stopped because of loss of clinical equipoise based on positive results from previous sotatercept trials. Results were published Sept. 30 by the New England Journal of Medicine.
The median duration of follow-up was 13.2 months. At that time, at least one primary end point event had occurred in 17 patients in the sotatercept group and in 59 patients in the placebo group (10.6% vs. 36.9%; hazard ratio, 0.24 [95% CI, 0.14 to 0.41]; P<0.001). Deterioration in performance on exercise testing due to PAH occurred in eight patients (5.0%) in the sotatercept group and 46 patients (28.8%) in the placebo group. Unplanned hospitalization for worsening of PAH occurred in three patients (1.9%) and 14 patients (8.8%), and death from any cause occurred in seven patients (4.4%) and six patients (3.8%), respectively. There were no cases of atrial septostomy or lung transplantation. The most common adverse events with sotatercept were epistaxis (31.9%) and telangiectasia (26.2%).
Limitations include that ending the trial early reduced the follow-up duration and limited enrollment, hindering longer-term safety and efficacy assessments and affecting the reporting of subsequent events, including deaths. Some patients did not reach the week 24 visit at which secondary end points were tested, so the results do not reflect longer-term efficacy, the authors noted.
The reduced risk of clinical worsening events with the drug was primarily driven by fewer cases of deterioration in performance in exercise testing, according to the authors. “Such events are considered to be important because nonfatal clinical worsening events in patients with PAH are associated with an increased risk of subsequent death, a relationship underscoring the need to monitor and prevent disease progression in these patients,” they wrote.