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Riociguat, a potent vasodilator that is the first in a new class of drugs, has been approved by the Food and Drug Administration for treating two types of pulmonary hypertension in adults.
The drug, which will be marketed as Adempas, was approved Oct. 8 to treat chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH), the agency said in a statement.
Orally administered in tablet form, riociguat is a soluble guanylate cyclase (sGC) stimulator, the first drug in this class to be approved for pulmonary hypertension. It is also "the first drug of any class to be shown to be effective for patients with CTEPH," Dr. Norman Stockbridge, director of the Division of Cardiovascular and Renal Drug Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
Riociguat is a pregnancy category X drug and is available to women only through a Risk Evaluation and Mitigation Strategy (REMS) program.
The approved indications for the drug, which will be marketed by Bayer HealthCare Pharmaceuticals, are for persistent/recurrent CTEPH (WHO group 4) "after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class" or PAH (WHO group 1) "to improve exercise capacity, improve WHO functional class, and to delay clinical worsening."
Approval was based on the results of two international studies that found treatment resulted in significant improvements over placebo in the 6 minute walk test. Side effects of treatment include headache, dizziness, dyspepsia, peripheral edema, nausea, diarrhea, and vomiting, according to the FDA. Based on these results, an FDA advisory panel unanimously recommended approval of the two indications in August.
In the study of 380 patients with PAH, the change from baseline in the 6-minute walk test at 12 weeks improved by a mean of 30 m among those treated with riociguat, vs. a mean drop of 6 m in the placebo group. The WHO functional class improved in 21% of those on riociguat, compared with 14% in the placebo group, deteriorating in 4% and 14%, respectively.
In the study of 261 patients with CTEPH, the change from baseline in the 6-minute walk test at 16 weeks improved by a mean of 39 m among treated patients vs. a mean 6 m reduction in the placebo group at 16 weeks. WHO functional class improved in 33% of those on riociguat and 15% of those on placebo, deteriorating in 5% and 7%, respectively.
The two studies were published in the July 25 issue of the New England Journal of Medicine (2013;369:330-40; 2013;369:319-29).
The prescribing information includes a boxed warning about embryo-fetal toxicity. Women can receive the drug only through the REMS program.
Because of the risk of hypotension, the drug is contraindicated for use with nitrates or nitric oxide donors, such as amyl nitrate, and with phosphodiesterase inhibitors or nonspecific PDE inhibitors.
The wholesale cost of the drug is $7,500 for 30 days of treatment, with one tablet taken three times a day, according to a Bayer spokesperson. The company has set up a patient assistance program to help with coverage.
To date, riociguat has been approved in Canada for the treatment of inoperable or persistent/recurrent CTEPH after surgery in adults with WHO functional class II or III pulmonary hypertension, and it is under review in the European Union, according to the company spokesperson.