FDA OKs New Drug for Pulmonary Hypertension

The FDA has approved riociguat (Adempas) for patients with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH).

The drug, a soluble guanylate cyclase stimulator, is the first to be cleared for use in CTEPH that has either not responded to pulmonary endarterectomy or is inoperable. It joins three other classes of drugs - phosphodiesterase type 5 (PDE5) inhibitors, prostanoids, and endothelin-receptor antagonists - that are already used for PAH.

The approval - which follows an FDA advisory panel’s unanimous support in August - was based on the results of the PATENT-1 trial in PAH and the CHEST-1 trial in CTEPH, which were reported earlier this year in the New England Journal of Medicine.

In CHEST-1, 16 weeks of treatment resulted in a significantly greater improvement - 46 meters (151 feet) - in 6-minute walk distance with riociguat compared with placebo.

In PATENT-1, in which riociguat was used either alone or in combination with endothelin-receptor antagonists or prostanoids, 12 weeks of treatment resulted in a similar advantage for the drug, with an average improvement that was 36 meters (118 feet) greater.

In both trials, riociguat also improved some secondary endpoints, including systemic vascular resistance and World Health Organization functional class.

The drug’s label will carry a boxed warning stating that the drug should not be used in pregnant women because of the risk of adverse effects on the fetus. Female—but not male—patients will be required to enroll in a Risk Evaluation and Mitigation Strategy (REMS) program in order to receive the drug.

“All female patients must be enrolled in the program, comply with pregnancy testing requirements, and be counseled regarding the need for contraception,” according to the FDA.

Anyone prescribing the drug also will be required to enroll in the REMS program, and pharmacies carrying the drug will have to be certified.

Aside from pregnancy, other contraindications to using riociguat include use at the same time as nitrates, nitric oxide donor drugs, and PDE inhibitors, including specific PDE5 inhibitors and nonspecific PDE inhibitors.

Riociguat received priority review from the FDA, which noted that the approval occurred despite the government shutdown because it “is an activity that is funded under the FDA’s user fee program in the Center for Drug Evaluation and Research (CDER). Some FDA activities that do not rely on annual appropriations are continuing during the government shutdown.”

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From the American Heart Association: