Positive Results Reported for Pulmonary Hypertension Drug Riociguat (Adempas) in Phase III Trial
One-year data show sustained improvement
After 1 year of treatment with riociguat (Adempas, Bayer), patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and those with persistent or recurrent pulmonary hypertension after an operation for the disease showed sustained improvement in an international trial presented at the 2014 American Thoracic Society International Conference, being held May 16–21 in San Diego, California.
Riociguat is a guanylate cyclase stimulator that works both independently and in concert with endogenous nitric oxide to induce vasodilation. A long-term extension study, CHEST-2, enrolled patients from CHEST-1, which had followed these patients for 16 weeks and had achieved its primary endpoint: improved 6-minute walking distance (6MWD).
“The pivotal study CHEST-1 showed significant improvements in exercise capacity and hemodynamics in patients treated with riociguat,” said principal investigator Marius Hoeper, MD. “However, the study was relatively short, and CHEST-2 adds important information on the long-term tolerability and efficacy of riociguat in patients with CTEPH.”
Approximately 5,000 people in the U.S. are diagnosed with CTEPH each year. The disease occurs when blood clots from previous episodes of acute pulmonary embolism do not resolve, causing persistent obstruction of the pulmonary vasculature, which may ultimately lead to pulmonary hypertension.
Pulmonary endarterectomy (PEA) is the treatment of choice for operable patients with CTEPH. However, not all patients are candidates for PEA (a long and complex procedure), and 20% to 30% of those who undergo the surgery are not cured. Therefore, there is an urgent medical need to develop effective drugs for patients with inoperable CTEPH or persistent pulmonary hypertension after PEA.
In the CHEST-2 trial, 172 patients (73%) had inoperable CTEPH and 65 (27%) had persistent or recurrent PH after PEA. Unlike in CHEST-1, which had a placebo arm, all patients received riociguat in the extension trial. The primary endpoint of CHEST-2 was safety and tolerability, which riociguat met. The drug was well tolerated by most of the patients; 4% of inoperable patients and 2% of patients with persistent or recurrent disease withdrew because of adverse events.
The researchers also reported data related to secondary endpoints: the change in 6MWD and the World Health Organization (WHO) functional class (a means of classifying disease severity in patients with pulmonary hypertension). Compared with the baseline established in the CHEST-1 trial, 6MWD was improved by 54 meters in the inoperable subgroup and by 44 meters in the persistent/recurrent subgroup after 1 year in the CHEST-2 study.
Similarly, when compared with the baseline in CHEST-1, the proportion of inoperable patients who showed improvement in their WHO functional class was 46% at 1 year in the CHEST-2 study. Fifty percent of the patients were stabilized, and 5% showed worsened function. The comparable percentages for the persistent/recurrent patients were 47%, 49%, and 0%.
Hoeper noted that, based on the data from the CHEST-1 and CHEST-2 studies, riociguat was recently approved in the U.S. for patients with inoperable or recurrent CTEPH.
Source: EurekAlert; May 19, 2014.