Actelion’s Opsumit Shows Promise as Treatment for Portopulmonary Hypertension, Trial Results Show

Actelion Pharmaceuticals’ Opsumit (macitentan) may be a potential therapy for portopulmonary hypertension, according to positive results from a Phase 4 clinical study.

The data was presented at the European Respiratory Society (ERS) meeting, held Sept. 15-19 in Paris.

The development of pulmonary arterial hypertension (PAH) in association with elevated pressure in the portal vein — responsible for directing blood from parts of the gastrointestinal tract to the liver — is known as portopulmonary hypertension (POPH).

POPH is a common complication of advanced liver disease, and while liver transplant is the most effective treatment strategy for these patients, severe PAH is a contraindication for this procedure as it reduces its chances of success and worsens the overall patient’s prognosis.

Therefore, it is important to first treat PAH in these patients so that they can undergo a liver transplant. However, since most clinical studies evaluating PAH treatments do not include POPH patients, evidence of their effectiveness in these patients is limited.

From June 2015 to October 2017, Actelion conducted the first-ever randomized, placebo-controlled, clinical study in POPH patients, called PORTICO (NCT02382016), which evaluated the safety and effectiveness of Opsumit in these patients.

Opsumit is an oral therapy approved in the U.S. and Europe for the treatment of PAH symptoms and to slow the progression of disease. It works by reducing the contraction and narrowing of blood vessels, which can help reduce their resistance to blood flow and lower blood pressure in the lungs.

The PORTICO Phase 4 study recruited 85 POPH patients, who were randomized to receive either 10 mg of Opsumit (43 patients) daily or a placebo (42 patients), for 12 weeks.

The study’s primary goal was the reduction of pulmonary vascular resistance. Secondary goals included the reduction of mean pulmonary arterial pressure (mPAP) and disease severity; an improvement in cardiac index (the amount of blood ejected by the heart in a unit of time divided by the body surface area); and improvement in the six minute walk distance test (which assesses exercise capacity and endurance).

Results showed that Opsumit treatment significantly reduced the patients’ pulmonary vascular resistance by 35%, and significantly improved mPAP and cardiac index, compared to patients receiving the placebo.

However, no significant differences in disease severity or in the six-minute walk distance test were found between the two groups.

Opsumit was generally well tolerated, and its safety profile was consistent with that reported in previous clinical trials, with swelling of the legs or arms and headache being the most common adverse events reported.

Overall, these findings point to Opsumit as a potential therapeutic strategy for patients with POPH.

“The findings of PORTICO are relevant because if patients with POPH can be treated to successfully lower pulmonary vascular pressure and resistance, more patients may be eligible for liver transplant as they will potentially have a better prognosis for this surgery,” Olivier Sitbon, an MD and PhD, the trial’s lead investigator, said in a press release.

“The fact that the hepatic [liver] safety profile of macitentan [Opsumit] in patients with POPH was consistent with that observed in previous trials is particularly reassuring, as POPH patients are typically excluded from PAH clinical trials on safety grounds,” he added.

Opsumit is also being investigated as a possible treatment for chronic thromboembolic pulmonary hypertension (CTEPH), another form of pulmonary hypertension for which Actelion has already requested an expanded approval in the U.S. and in Europe.