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FDA turnabout: United Therapeutics’ ‘oral Remodulin’ cleared in PAH

By Randy Osborne

Staff Writer

United Therapeutics Corp. was trading high in the wake of the late Friday approval by the FDA of Orenitram (treprostinil) extended-release tablets for pulmonary arterial hypertension (PAH). Already cleared as an injectable drug known as Remodulin, the compound’s oral version in October garnered a complete response letter (CRL) from the agency, which found the data package less than acceptable. The win came after United submitted its new drug application (NDA) for the third time, and without providing more post-CRL data to the FDA.

Shares of the Silver Spring, Md.-based company’s stock (NADSDAQ:UTHR) were selling midmorning at $106.88, up $19.04, or 21 percent.

Orenitram marks the first time that the FD4 has approved an orally administered prostacyclin analogue for any disease and United’s fifth approval for treatment of PAH. It’s also “arguably, one of the top 10 biggest upside surprises in the history of the biotech sector,” wrote ISI Group analyst Mark Schoenebaum, in an email to investors.

United’s main efficacy study, called FREEDOM-M, showed that patients receiving Orenitram twice daily improved their median six-minute walk distance (6MWD) by 23 meters (p=0.013) as compared to patients receiving only placebo.

As the sole vasodilator, Orenitram’s effect on exercise is small and Orenitram has not been shown to add to other vasodilator therapy, the company noted. A pair of other Phase III trials, known as FREEDOM-C and FREEDOM-C2, did not demonstrate a benefit in exercise with median walk test at week 16 (11 meters [p=0.072] and 10 meters [p=0.089], respectively).

The FDA said yes, anyway, and well ahead of the Feb. 16, 2014, PDUFA date. Orenitram’s total daily dose can be divided and given three times daily with food, and the tablet comes in four strengths:  0.125 mg, 0.25 mg, 1 mg and 2.5 mg, with the maximum dose per patient determined by tolerability.

RBC Capital Markets analyst Michael Yee wrote in a research report that the FDA “appears to be clearing the queue at year-end,” pointing out that Cambridge, Mass.-based Ariad Pharmaceuticals Inc.’s leukemia drug Iclusig (ponatinib) was approved earlier the same day. (See BioWorld Today, Dec. 23, 2013.)

Although the approval is a definite positive for United, Yee wrote, “it's only around a $250 million franchise,” and faces a major competitive risk in selixipag, the oral prostacyclin receptor agonist for which Actelion Ltd., of Allschwil, Switzerland, has Phase III data due next year.