The US Food and Drug Administration approved an update to the sotatercept-csrk (Winrevair) label to include efficacy and safety data from the phase 3 HYPERION trial in adults recently diagnosed with pulmonary arterial hypertension, according to a Merck press release. Sotatercept is approved in adults with pulmonary arterial hypertension (World Health Organization Group 1 pulmonary hypertension) to improve exercise capacity and functional class and reduce the risk of clinical worsening events.
The global, double-blind, placebo-controlled HYPERION trial included 320 adults with World Health Organization functional class II or III pulmonary arterial hypertension diagnosed within 12 months of screening who were at intermediate to high risk of disease progression. Investigators randomly assigned 160 participants to subcutaneous sotatercept at a target dose of 0.7 mg/kg and 160 to placebo once every 3 weeks. All participants were receiving background pulmonary arterial hypertension therapy. The trial was stopped early based on positive results from an interim analysis of ZENITH and a review of data from the sotatercept clinical program.
The primary efficacy end point was time to the first confirmed clinical worsening event, defined as mortality or the first confirmed morbidity event. Events included all-cause mortality, unplanned pulmonary arterial hypertension–related hospitalization lasting at least 24 hours, atrial septostomy, lung transplantation, or decreased 6-minute walk distance from baseline accompanied by worsening functional class, signs or symptoms of increased right heart failure, or addition or change in background therapy.
A first clinical worsening event occurred in 11% (17 of 160) of patients receiving sotatercept and 37% (59 of 160) receiving placebo. Sotatercept reduced the risk of clinical worsening events by 76% compared with placebo. The mean time since pulmonary arterial hypertension diagnosis was 7 months. Overall, 72% of participants were receiving double background therapy, 28% were receiving triple therapy, and 17% were receiving prostacyclin infusion therapy.
Safety findings in HYPERION were generally consistent with those from STELLAR. The most common adverse reactions were epistaxis (32% vs 7%), telangiectasia (26% vs 11%), and increased hemoglobin (11% vs 1%). Adverse events led to treatment discontinuation in 3% of patients receiving sotatercept, most commonly because of epistaxis, compared with no discontinuations among patients receiving placebo.
The updated label also contains additional safety information regarding serious hypersensitivity reactions. Sotatercept is contraindicated in patients with serious hypersensitivity to sotatercept-csrk or its excipients. Health care providers should monitor hemoglobin and platelet levels before each of the first 5 doses, or longer if values are unstable, and periodically thereafter.
Source: Merck
