Quick facts: Why was the ZENITH sotatercept study stopped?

The ZENITH study looked at some of the sickest pulmonary arterial hypertension (PAH) patients—those labelled as functional class 3 (people who find normal chores around the house leave them tired or breathless) or 4 (people who have symptoms even when they are resting) and who were at high risk of mortality. The goal of the study was to see if sotatercept would reduce patients’ risks of death, needing a lung transplant, or having to be admitted to hospital due to their PAH.

When the researchers designed the study, they randomly divided study participants into two groups. One group received sotatercept on top of their normal therapies. The other group received a placebo and their normal therapies. Neither the patients in the study nor the researchers knew who was in the sotatercept group and who was in the placebo group.

Researchers planned to look at the data when the study was half over. When they looked at this early data, it showed "overwhelming efficacy": they found that patients in the sotatercept group had a 76% lower risk of death, needing a lung transplant, or having to be admitted to hospital due to their PAH than patients in the placebo group.

The researchers didn’t know whether sotatercept would be better than a placebo for these patients. When sotatercept did so much better than the placebo in the early analysis, the researchers stopped the study so all patients in the study could benefit from sotatercept.

All the patients in the ZENITH study—people in the placebo group as well as people who had received sotatercept—will be able to receive sotatercept through the ongoing SOTERIA extension study.

Dr. Lisa Mielniczuk talked about this in her recent presentation to the Ottawa PH Support group:

If you’d like to know more, you can read the New England Journal of Medicine article here.