Adempas Seen to Benefit Idiopathic PAH Patients Who Fail to Respond to Revatio in Pilot Study

Adempas was also seen to ably help treatment-naive patients, using it as a first PAH therapy.

The study, “Initial Riociguat Monotherapy and Transition from Sildenafil to Riociguat in Patients with Idiopathic Pulmonary Arterial Hypertension: Influence on Right Heart Remodeling and Right Ventricular–Pulmonary Arterial Coupling,” was published in the journal Lung.

For years, the only therapies available to alleviate the symptoms of IPAH were so-called phosphodiesterase type 5 inhibitors, like sildenafil, sold by Pfizer under the brand name Revatio in the U.S. But not all patients respond to Revatio or other such inhibitors, even when used as combination treatments.

Riociguat, marketed by Bayer as Adempas, is an approved PAH therapy. Both Revatio and Adempas relax and widen the blood vessels, but they do so in different ways. In fact, the therapeutic action of Adempas is potentially stronger than that of phosphodiesterase type 5 inhibitors.

In a pilot study, researchers tested the effectiveness of Adempas in lessening various symptoms linked with IPAH in a group of patients who had never received a treatment (treatment-naive) and a group who failed to respond to Revatio. All participants were being treated at a specialty hospital in Russia.

Specifically, the team assessed treatment in patients using the World Health Organization functional class (WHO FC) — in which the higher the FC, the more severe is the disease — the 6-minute walk test (6MWT; to assess exercise capacity), and parameters that measure heart function, namely right heart remodeling and right ventricular–pulmonary arterial (RV-PA) coupling.

These last measures are important to evaluate as the disease can damage the heart’s right ventricle and cause it to fail.

WHO FC, 6MWT, right heart remodeling, and RV–PA coupling were all assessed at study entry (baseline) and following 12 weeks of treatment with Adempas.

In total, the study enrolled 20 patients with idiopathic PAH (ages 35.7 to 50), 12 who were treatment naive, and eight who had been using Revatio for a median of 21.5 months but failed to respond to the therapy.

All patients were given Adempas up to a maximum dose of 2.5 milligrams (mg) three times a day. The dose was tailored to each patient.

At baseline, 67% of patients in the treatment-naive group were classified as WHO FC III (eight people), and had a mean 6MWT of 381 meters. Among those who switched from Revatio to Adempas, 50% (four patients) were in WHO FC III before any therapy initiation (Revatio or Adempas), and had a mean 6MWT of 371 meters.

Overall, after 12 weeks on Adempas, both groups showed a significant improvement in WHO FC and 6MWT compared to baseline (mean change of 76 meters), the study reported.

In the treatment-naïve group, the WHO FC III score dropped scores in three patients (two became FC II and one FC I), and had a mean increase of 76.8 meters in the 6MWT at 12 weeks.

In the group that switched from Revatio to Adempas, one patient improved in WHO FC score (from FC III to FC I), and had a mean increase in 6MWT of 71.6 meters.

Echocardiography at week 12 showed that Adempas treatment  lessened several of the heart disease parameters, including pulmonary arterial pressure.

“In conclusion, riociguat treatment demonstrated a positive effect on functional status, RV–PA coupling, and right heart remodeling in treatment-naïve patients with IPAH and in patients with IPAH who failed to achieve treatment goals with sildenafil and who were switched to riociguat,” the researchers wrote.

“This suggests that transitioning from sildenafil to riociguat may be an effective therapeutic strategy in patients with IPAH who fail to have an adequate treatment response to PDE5i [phosphodiesterase type 5 inhibitors],” and “suggest[s] that it may be possible to delay disease progression in this patient group,” the team concluded.