An experimental medicine for a rare blood vessel disorder improved patients’ exercise capacity and potentially slowed the disease’s progression, according to detailed results from a late-stage clinical trial that were revealed on Monday.
The drug, called sotatercept and owned by Merck & Co., was the principal prize of an $11.5 billion acquisition the pharmaceutical company negotiated more than a year ago.
Data from the trial were presented at a medical conference and published in The New England Journal of Medicine. They have been highly anticipated since October, when Merck said the study, dubbed STELLAR, was a success.
Study volunteers had pulmonary arterial hypertension, or PAH, which is caused by a thickening of the blood vessels around the lungs. The condition makes it more difficult for the heart to push blood through the lungs, and can lead to heart failure as well as early death.
Participants who received sotatercept alongside standard treatment walked, by one statistical comparison, 34 meters further over six minutes than those who received a placebo and those other drugs. This so-called six-minute walk test, the study’s main goal, is a common measure used in trials of cardiovascular disease drugs.
A difference of 30 meters is considered to be the lower bar for a clinically meaningful outcome, according to three physicians who, in an editorial accompanying the study publication, called the data “impressive.” (By another statistical analysis, known as a Hodges–Lehmann estimate, the difference between groups was nearly 41 meters.)
“The STELLAR trial provides encouraging data for a new direction in therapeutic strategies for pulmonary arterial hypertension, and it forces us to ask whether a new treatment era for the disorder has arrived,” the physicians, all specialists in PAH and cardiovascular medicine, wrote.
But, they added, “it’s too soon to know,” given unanswered questions about the drug’s results in children and adults who are sicker than those enrolled in Merck’s study.
Encouragingly, treatment with sotatercept was associated with an 84% lower risk of death or disease progression compared to placebo. “This is something we've never seen before with any other drug,” Marius Hoeper, deputy director of the respiratory medicine department at Hannover Medical School in Germany and the study’s lead investigator, in an interview.
On standard medicines, patients with a progressive form of PAH typically live between five to seven years after diagnosis — an improvement from the two to three years before there were treatments. While Merck’s study was not specifically designed to show the drug helps prolong survival, Hoeper said he expects the drug will extend the lives of patients “substantially.”
PAH is usually treated with medicines that dilate the blood vessels in the lungs, such as Letairis. Other, newer medicines include the Johnson & Johnson drugs Opsumit and Uptravi.
Sotatercept, which was developed by the biotechnology company Acceleron before its acquisition by Merck, could become the first treatment of its type. It acts on certain biological pathways that lead to a thickening of the blood vessel walls and, in turn, hypertension.
“We have a drug that acts on the underlying mechanisms that drive this pulmonary arterial hypertension,” Hoeper said. “We believe that we do see some reopening of formerly occluded, or obstructed, pulmonary vessels.”
Beyond the walk test, the drug showed benefits in heart function and pulmonary vascular resistance that exceeded gains seen for other tested treatments in similar patients, he added.
In the study, patients who received the drug had mild side effects such as nose bleeds, gum disease and dizziness more often than those in the placebo group. As sotatercept is the first drug of its kind, patients will need to be closely monitored, Hoeper said.
Merck’s shares closed Monday trading up nearly 4%.
“We look forward to discussing these pivotal data with health authorities and are working with urgency to bring this potential new treatment option to patients,” said Dean Li, president of Merck Research Laboratories, in the company’s statement.