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Actelion’s PAH Drug Opsumit Cleared; No Liver Monitoring

By Randy Osborne
Staff Writer

The first therapy for pulmonary arterial hypertension to be approved on endpoints measuring patient function rather than outcomes such as the 6-minute walk test won the FDA’s blessing Friday.

And it came, as many had hoped, without a black-box warning about elevated liver enzymes.

Allschwil, Switzerland-based Actelion Ltd.’s Opsumit (macitentan), a next-generation dual endothelin receptor antagonist (ERA), showed in a long-term randomized, controlled study that morbidity and mortality got significantly better.

The once-daily, oral drug is given at a 10 mg dose to delay progression of PAH. Actelion filed its new drug application for Opsumit about a year ago. (See BioWorld Today, Oct. 24, 2012.)

Roland Haefal, senior vice president of public affairs, said Opsumit will launch shortly. ”It will take a few days, so sometime in November, the drug will be commercially available,” he told BioWorld Today. “The label now needs to be printed and shipment needs to be prepared.”

Approval of Opsumit came less than week after the FDA cleared for marketing Adempas (riociguat) tablets from Bayer Healthcare Inc., of Whippany, N.J., for PAH and for persistent/recurrent chronic thromboembolic pulmonary hypertension. While Opsumit advances the ERA class, Adempas is the first of a new set of soluble guanylate cyclase stimulators.

For Actelion, Opsumit serves as the successor to Tracleer (bosentan), a blockbuster that goes off patent in 2015. First-half 2013 sales of Tracleer rose less than 2 percent from the previous year, at CHF766.9 million (US$850.3 million), compared to CHF752.4 million in the first half of 2012. Overall, Actelion’s product sales rose 2.6 percent, to CHF884.1 million, in the first half of 2013 from CHF861.8 during the same period in 2012.

Approval of Opsumit was widely anticipated, and investors were more interested in the label language, especially any that might require liver monitoring. This has an effect on sales, as shown by the upswing in sales of ERA competitor Letairis (ambrisentan, Gilead Sciences Inc.) after the FDA removed its mandate on liver-enzyme tests for that product in March 2011.

“In regulatory parlance, with ambrisentan, they had a class assumption with [required] post-marketing surveillance,” said Haefal. “That class assumption was lifted. As such macitentan was open for free evaluation.”

The U.S. label for Opsumit carries a boxed warning that relates to pregnant women, or teratogenicity, which is standard, Haefal said. Doctors are advised to measure hemoglobin and liver enzymes before starting Opsumit, and to repeat during treatment “as clinically indicated.”

In PAH, “the disease by itself is exerting pressure on the organs, so it is a standard occurrence in PAH patients that some of them have elevated liver enzymes,” Haefal said, noting that the large, two-year trial on which Opsumit’s application was based gave proof that the drug does not boost enzymes. The experiment was the largest and longest randomized, controlled study in PAH patients to include a clearly defined morbidity/mortality primary endpoint.

In a research report, Jefferies analyst Peter Welford forecast $1.4 billion in peak sales of Opsumit, “assuming 40 percent new PAH patient share, with little switching, at a 15 percent price discount to Tracleer and Letairis. Clinician feedback on Opsumit is almost unanimously encouraging, suggesting relatively rapid and broad adoption as the ERA drug of choice, based on unique morbidity-mortality claims, with payers the only major hurdle for blockbuster potential, in our view,” he wrote.