Adempas Aids PAH Patients Not Improving on PDE5i Therapy, Clinical Study Finds

Patients with pulmonary arterial hypertension (PAH) who fail to benefit from treatment with phosphodiesterase 5 inhibitors (PDE5i) may safely switch to Adempas (riociguat), according to the final results of a clinical trial, which showed that Adempas improved their health.

The results were presented at the European Respiratory Society (ERS) International Congress 2016, held in London from Sept. 3–7, in an oral presentation titled “RESPITE: Riociguat in pulmonary arterial hypertension patients with an inadequate response to phosphodiesterase type 5 inhibitors.”

Adempas, which was approved by the U.S. Food and Drug Administration for PAH treatment in 2013,  stimulates a molecule known as soluble guanylate cyclase. Several clinical trials have shown that the drug is effective in managing PAH. Now, researchers assessed if Adempas might also aid patients wishing to switch from PDE5i treatment.

The Phase 3b clinical trial (NCT02007629) is a one-arm open-label study, meaning that all patients received Adempas and were aware of the treatment. The study enrolled patients in WHO functional class III, meaning they could walk between 165 and 440 meters in the 6-minute walk distance test. Participants also needed to have low heart function (cardiac index <3.0 L/min/m2) despite PDE5i treatment alone or in combination with an endothelin receptor antagonist (ERA).

Of the 61 eligible PDE5i patients, 66 percent used Revatio (sildenafil) and another 34 percent were taking Adcirca (tadalafil). Most of these patients, 82 percent, were also receiving ERA treatment. Following a PDE5i washing-out period, patients started treatment with Adempas.

After 24 weeks, all measures of efficiency — including exercise capacity, blood flow dynamics and WHO functional class — improved with the switch to Adempas. Six  patients, equalling 10 percent, experienced clinical worsening events during the trial, including two deaths, but none of the deaths were related to treatment.

“The findings from RESPITE indicate that PAH patients with insufficient response to PDE5i, as defined in this trial, may benefit from transition to Adempas, as demonstrated through the exploratory trial endpoints,” Professor Marius M. Hoeper, with the Department of Respiratory Medicine, Hannover Medical School, Germany, and the lead RESPITE investigator, told Pulmonary Hypertension News.

The most common side effects reported were headache, indigestion, and nose bleeds. Four patients stopped the treatment after experiencing severe side effects, such as right ventricular failure and shortness of breath. These adverse effects are known from earlier studies with Adempas.