Prof. Marius Hoeper
Patients with pulmonary arterial hypertension (PAH) may benefit from a novel first-in-class medication sotatercept and from use of a fixed-dose combination pill of existing therapies, according to two studies presented at the American College of Cardiology’s Annual Scientific Session (ACC23).
Results from an international, multicentre phase 3 trial involving 323 patients with PAH showed that those assigned to receive sotatercept on top of existing therapy experienced significant improvements in six-minute walk distance test (6MWD), the study’s primary endpoint.
Patients who received sotatercept also had a lower risk of death or worsening of their condition compared with patients on standard therapy.
Sotatercept is a fusion protein activin signalling inhibitor that blocks abnormal patterns of growth differentiation factors involved in PAH.
The Phase 3 STELLAR trial enrolled 323 adult patients (median age 48 years, 79% women) with PAH (WHO functional class II or III) who were receiving stable background therapy, of whom 60% had severe symptoms despite maximal therapy with three medications.
After a median follow up of 7.5 months the average improvement in 6MWD among patients receiving sotatercept was 40.8 meters, while patients who received the placebo showed no improvement.
The change was statistically significant and exceeded the clinically relevant benchmark of a minimum of 33 meters at which patients report a noticeable improvement in their walking capacity, said study investigators.
Patients receiving sotatercept also showed improvements in eight of nine secondary endpoints, including functional class, proBNP levels and several measures of quality of life.
Nine patients (5.5%) in the sotatercept group died or experienced at least one clinical worsening event, compared with 42 (26.3%) in the placebo group, a risk reduction of 84%.
Patients in the sotatercept groups also had statistically significant improvements in symptoms such as shortness of breath and fatigue, as well as in the ability to perform activities such as light household chores, whereas patients on placebo showed no improvements.
In addition, the sotatercept group saw a reduction in pulmonary arterial pressure, or blood pressure in the lungs, that was 13.9 mmHg larger than was seen in the placebo group.
“This is the most impressive reduction in the pulmonary arterial pressure that we’ve ever seen in pretreated patients with PAH,” said study investigator Professor Marius Hoeper of Hannover Medical School, Germany. “For me, it’s one of the strongest signals suggesting that we truly achieved some regression of the disease’s adverse changes in the pulmonary vessels. However, this remains a hypothesis that we need to explore in future studies.”
Sotatercept appeared to be safe and well tolerated, with adverse events including mild nose bleeds and bleeding of the gums, telangiectasias, increases in haemoglobin levels and lower platelet counts.
Professor Hoeper said the results establish the clinical utility of sotatercept as a new approach to the treatment of PAH in combination with existing approved therapies.
“It’s really a paradigm shift in how we will treat PAH in the future … what we see in our clinic is fascinating—patients who have been evaluated for lung transplantations coming off the transplant list, patients returning to work, young patients who have been ill for most of their lives starting at their first jobs. [This treatment] opens the door to further research aiming at restoration of a normal pulmonary blood flow.”
