Adempas Benefits Pulmonary Hypertension Patients Long Term, Phase 2 Clinical Trial Shows

The lung functioning of pulmonary hypertension patients treated with Bayer’s Adempas improved by 50 percent over a median of six years and stabilized in another 45 percent, according to a Phase 2 clinical trial.

Those findings and others indicate that Adempas is a good long-term therapy for pulmonary arterial hypertension, or PAH, and inoperable chronic thromboembolic pulmonary hypertension, or CTEPH, researchers said.

The study, published in the journal Respiratory Medicine, was titled “Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study.”

PAH and CTEPH are severe and progressive diseases. Their hallmark is an increase in resistance to blood flowing through the vessels that convey it to the lungs, a condition known as pulmonary vascular resistance. This impaired flow can ultimately lead to right heart failure and death.

The main cause of PAH is rearrangement of small pulmonary arteries, scientists say. The main cause of CTEPH is blood clotting in the lungs, but the disease can also have the vascular remodeling seen in PAH.

PAH can be treated with soluble guanylate cyclase stimulators like Adempas. A guanylate cyclase stimulator is an enzyme that’s crucial to the proper functioning of the nitric oxide signaling pathway. That pathway promotes vasodilation, or widening of blood vessels so more blood can flow to the lungs.

A surgery called endarterectomy is the treatment most doctors prefer for CTEPH. It relieves pulmonary artery obstruction by correcting stenosis, or narrowing of the arteries.

About a third of patients cannot be operated on, however, and others develop persistent or recurrent pulmonary hypertension after surgery. The key option for this group is medicine.

In the open-label Phase 2 clinical trial (NCT00454558), researchers evaluated Adempas’ long-term effectiveness, safety and tolerability in 41 CTEPH and 27 PAH patients.

The team used four yardsticks to analyze patient’s lung-function improvement. One was a measure of exercise capacity known as the six-minute walking distance. The other was the World Health Organization pulmonary hypertension functional class, or WHO FC. A third was patients’ overall survival, and the fourth was clinical worsening-free survival, or the amount of time it took for a patient’s condition to worsen.

The distance that patients could walk in the six-mile walking distance test improved at 48 months, researchers found. In addition, WHO FC class improved in 50 percent of the patients and stabilized in 45 percent.

Ninety-one percent of patients were still alive at three years. Forty-nine percent of the patients had not experienced a worsening of their condition by then.

Researchers attributed the high rate of clinical worsening to the patients shifting to a new PH treatment.

Adempas was found to be well tolerated.

The study drop-out rate was high, with 47 percent of patients discontinuing treatment before the cut-off. One reason was probably the duration of the treatment — a median of 77 months, researchers said. Another was that Adempas was an experimental drug at the time, increasing the probability that either the doctor or patient would interrupt the treatment.