FDA approves first drug to treat two forms of pulmonary hypertension

October 10, 2013

Before the approval of riociguat, there was no approved nonsurgical therapy for chronic thromboembolic pulmonary hypertension.

FDA has approved riociguat (Adempas, Bayer HealthCare Pharmaceuticals) tablets for the treatment of adults with chronic thromboembolic pulmonary hypertension (CTEPH) after surgical treatment, adults with inoperable CTEPH, and adults with pulmonary arterial hypertension (PAH).

“The approval of Adempas equips physicians with a new treatment option for patients with PAH and CTEPH, two life-threatening forms of pulmonary hypertension,” said Pamela A. Cyrus, MD, vice president and head, U.S. medical, Bayer HealthCare Pharmaceuticals. “Adempas is now the only treatment approved in the United States for use in two types of pulmonary hypertension [WHO Group 1 and 4]. It is the only FDA-approved drug therapy for persistent/recurrent CTEPH after surgical treatment or inoperable CTEPH. The standard treatment for CTEPH is and should remain pulmonary endarterectomy, a surgery that clears clots and scar material from the blood vessels of the lung. However, 20% to 40% of patients have inoperable CTEPH, and the disease persists in up to 35% of those who do undergo surgery.”

Before the approval of riociguat, there were no approved nonsurgical therapies for CTEPH, Dr. Cyrus said.

Action

Riociguat, a stimulator of soluble guanylate cyclase (sGC), represents a new drug class. With its novel mode of action, riociguat has the potential to overcome a number of limitations that characterize other approved PAH therapies, including nitric oxide (NO) dependence. Currently available therapies for PAH fall into three main categories: Endothelin receptor antagonists (ERAs), phosphodiesterase inhibitors (PDE5 inhibitors), and prostacyclins.

In the clinical trials for PAH, efficacy was shown in patients on riociguat monotherapy or in combination with ERAs or prostanoids (inhaled, oral, or subcutaneous). 

Pulmonary hypertension is associated with endothelial dysfunction, impaired synthesis of nitric oxide (NO), and insufficient stimulation of the NO-sGC-cGMP pathway. Riociguat sensitizes sGC to endogenous NO by stabilizing the NO-sGC binding. Riociguat also directly stimulates sGC via a different binding site, independently of NO. Riociguat restores the NO-sGC-cGMP pathway and leads to increased generation of cGMP with subsequent vasodilation.

Safety

Riociguat is contraindicated with coadministration of nitrates or nitric oxide donors, such as amyl nitrite, in any form, and with concomitant administration with PDE inhibitors. The drug is also contraindicated in pregnancy, as it may cause fetal harm when administered to a pregnant woman. For all female patients, riociguat is available only through the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program. 

The most common adverse reactions occurring more frequently on riociguat than placebo were headache, dyspepsia/gastritis, dizziness, nausea, diarrhea, hypotension, vomiting, anemia, gastroesophageal reflux disease, and constipation. Other events that were seen more frequently in riociguat compared to placebo and that were potentially related to treatment were palpitations, nasal congestion, epistaxis, dysphagia, abdominal distension, and peripheral edema.

Cost

According to Dr. Cyrus, riociguat costs $7,500 for 30 days of treatment consisting of one tablet taken orally three times per day.

“This price is comparable to most branded oral therapies approved to treat PAH,” she said.