Sotatercept improves blood flow, heart health in PAH: STELLAR trial
Phase 3 study had already shown sotatercept can enhance walking abilities
Treatment with sotatercept in addition to standard pulmonary arterial hypertension (PAH) therapies significantly improved measures of heart health for adults with the disease, according to a new analysis of the STELLAR trial.
Results from the Phase 3 trial had already shown the therapy enhanced walking abilities in the participants and led to improvements in most secondary measures, including an extension in the time to death or clinical worsening events.
The latest findings were shared in an oral presentation at the recent European Respiratory Society (ERS) International Congress 2023, and simultaneously published in the European Respiratory Journal in a study, titled “Effects of sotatercept on haemodynamics and right heart function: analysis of STELLAR trial.” The work was funded by sotatercept’s developer Acceleron Pharma, which is now a subsidiary of Merck (known as MSD outside North America).
“These latest data build on the clinically meaningful efficacy results from the STELLAR trial and support our belief that sotatercept has the potential to transform the treatment of PAH,” Eliav Barr, MD, senior vice president and head of global clinical development, chief medical officer at Merck Research Laboratories, said in a company press release.
PAH is marked by high pressure in the vessels that carry blood from the heart to the lungs. In PAH, cells in these vessels start growing more than they should, causing the vessels to narrow and ultimately increasing pressure. Sotatercept is designed to change the activity of certain signaling molecules to reduce this abnormal disease-driving growth.
STELLAR trial tested whether sotatercept improves exercise capacity in patients
The Phase 3 STELLAR clinical trial (NCT04576988) tested sotatercept against a placebo, given on top of standard medications, in 323 adults with PAH. The trial’s main goal was to evaluate whether sotatercept could improve exercise capacity, as evaluated by the distance patients could walk in six minutes, after six months of treatment.
Results showed the study met its goal, with patients given sotatercept being able to walk on average about 40 meters (131 feet) more compared with those given a placebo. The treatment also significantly reduced levels of NT-proBNP, a marker of heart damage.
In the new study, scientists looked at data from STELLAR to assess the effect of sotatercept on various measures of blood flow and heart health. This was a post-hoc analysis, meaning it was designed and carried out after the trial was over and all the data made available.
The researchers looked at data on right heart catheterization, which is an invasive technique used to assess blood flow in the lung’s blood vessels, from 298 patients. They also assessed echocardiography, which uses sound waves to visualize the heart, from 275 patients.
PAH can strain the heart and lead to eventual right heart failure, so we are particularly encouraged by the exploratory analysis from STELLAR suggesting that treatment with sotatercept improved right heart size and function.
Results from right heart catheterization data showed that, relative to placebo, sotatercept led to statistically significant improvements in several key clinical measures, including mean pulmonary arterial pressure (an assessment of pressure in the lung’s blood vessels) and pulmonary vascular resistance (a measure of the resistance to blood flow in the lung’s vessels).
The treatment also decreased pressure in the heart’s upper right chamber, and improved pulmonary artery compliance (the ability to distend and change volume in response to changes in pressure).
Echocardiography data showed some favorable changes associated with sotatercept. In particular, the therapy led to reductions in the size of the right ventricle, which is the part of the heart that pumps blood out to the lungs and typically becomes enlarged due to strain in PAH.
“PAH can strain the heart and lead to eventual right heart failure, so we are particularly encouraged by the exploratory analysis from STELLAR suggesting that treatment with sotatercept improved right heart size and function,” Barr said.
“In this exploratory post hoc analysis of the phase 3 STELLAR trial, 24 weeks of treatment with the activin signalling inhibitor sotatercept improved [blood flow and echocardiography] parameters in participants with PAH who were pre-treated with approved medications,” the scientists concluded.
Several improvements significantly correlated with distance walked in test
Further statistical tests showed that several of the improvements in these measures were significantly correlated with distance walked during the six-minute walk test, or with levels of NT-proBNP.
The researchers stressed that this was an exploratory analysis covering a relatively short period, emphasizing a need for additional research into the effects of sotatercept on heart health in PAH.
“Acknowledging the exploratory nature of these findings, this is the first clinical evidence suggesting that sotatercept may positively impact certain measures of right heart function and dimensions. This is encouraging and further supports the primary results from the STELLAR analysis, underscoring the potential of sotatercept to play a critical role in the treatment of PAH,” said Vallerie Mclaughlin, MD, an investigator in the STELLAR trial and director of the Pulmonary Hypertension Program at the University of Michigan.
Participants who completed STELLAR or other trials of sotatercept had the option to enter an open-label trial called SOTERIA (NCT04796337), which is collecting data on the long-term efficacy and safety of the therapy. Merck also presented interim data from SOTERIA at the ERS meeting.
Findings showed that, for 131 patients who had been on sotatercept for at least a year, improvements in six-minute walk distance and NT-proBNP levels that were seen after six months were generally maintained out to a year. Safety data from more than 400 patients treated in the extension study have so far been largely consistent with earlier data.
“The SOTERIA study provides us with important insight into the longer-term safety and efficacy of sotatercept,” said Ioana Preston, MD, director of the Pulmonary Hypertension Center and associate professor at Tufts University School of Medicine. “These results support the potential durability of clinical benefit and safety of sotatercept for the treatment of PAH.”