Caught off guard by the FDA’s approval – and ahead of schedule, to boot – of Orenitram (treprostinil) extended-release tablets for pulmonary arterial hypertension (PAH), United Therapeutics Corp. plans to launch the product within the next six months.

But analysts, and the company, are waiting until results from a mortality/morbidity trial with Orenitram, called FREEDOM-EV, before speculating too precisely about potential revenue gains.

“Certainly, with a positive result from [the FREEDOM-EV] study, there will be a different peak revenue potential” than without it, said Martine Rothblatt, CEO of Silver Springs, Md.-based United during a conference call with investors.

Those data are due in a few years. Meanwhile, United is readying the product for shipping. “Ordinarily, we would launch within 90 days,” said Rothblatt, but thanks to the “very pleasant surprise” delivered Friday by the FDA, the process will take somewhat longer. The PDUFA date was Feb. 16, 2014.

Orenitram is approved for use against PAH in World Health Organization (WHO) Group I patients to improve exercise capacity. WHO classifies PAH in five categories, depending on disease mechanisms.

Already available in subcutaneous and intravenous versions (Remodulin), with an inhaled form (Tyvaso) as well, the oral synthetic analogue of prostacyclin in October garnered a complete response letter, its second, from the agency. (See BioWorld Today, Oct. 25, 2012.)

ISI Group analyst Mark Schoenebaum reminded investors in an email over the weekend that the FDA has rejected the drug twice before and “with no additional data, United filed for a third time earlier this year. Amazingly, the FDA approved the application.”

Figuring out the financial impact for United comes next. “Bears will scream, ‘This will be a small drug,’” Schoenebaum predicted. “But the problem with that logic is that even it sells just $100 million, that could add about $1 (about 10 percent) to [United’s] earnings per share.”

Rothblatt did not want to disclose pricing yet.

“I would like us to shy away from setting any specific revenue guidance or peak sales guidance for Orenitram, because it is a new agent in a field with several other oral treatments for PAH,” she said, adding that it’s “necessary for us to gain some amount of the experience with the use or Orenitram in the marketplace.”

The price will be set per milligram (mg), she said, so that it’s “roughly equivalent to Tyvaso,” and United would be “revenue agnostic, whether a patient is on Tyvaso or Orenitram.” Tyvaso, Rothblatt added, “appears to be on track to catch up with Remodulin, perhaps by the end of 2014.”

Orenitram is given twice or three times daily and available in four strengths: 0.125 mg, 0.25 mg, 1 mg and 2.5 mg. The maximum dose per patient is determined by tolerability.

Selexipag red flag

Whether the oral version will significantly cut into sales of the other treprostinils remains an open question, and even Orenitram’s label seems to touch upon the possibility, describing the compound as “probably most useful to replace subcutaneous, intravenous or inhaled treprostinil, but this use has not been studied.”

United’s main efficacy study, called FREEDOM-M, showed that patients receiving Orenitram twice daily improved their median six-minute walk distance 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 label further says that, “when used as the sole vasodilator, the effect of Orenitram on exercise is about 10 percent of the deficit, and the effect, if any, on a background of another vasodilator is probably less than this.”

Roger Jeffs, president and chief operating officer of United, said during the conference call that the company has been “very specific in what we achieved in our clinical studies and what we did not achieve. The data are there for physicians and patients to consider, in terms of when they add therapy and how they add therapy.”

Leerink Swann analyst Joseph Schwartz estimated in a research report that Orenitram likely would sell about $250 million annually, at peak. In April 2012, Medacorp surveyed 50 physicians who treat almost 10,000 PAH patients in the U.S., and found that about 19 percent of their patients would be candidates for the oral drug if approved with the monotherapy indication, and 36 percent of doctors said they would try to use it off-label in combination with other therapies, among 27 percent of their patients.

Leerink’s top sales guess assumes uptake in about 2,500 PAH patients, and includes only a 25 percent probability that the FREEDOM-EV study will yield positive results, Schwartz wrote.

United’s shares (NADSDAQ:UTHR) closed Monday at $114.51, up $26.67, or 30 percent – a jump that RBC Capital Markets analyst Michael Yee called “outsized,” likely due in part to traders covering their short positions and “illiquidity at year-end,” he wrote in a research report. “We think investors will ultimately take profits here, as management was also relatively cautious about market size and declined any revenue projections, due to multiple factors including competition [and the] future FREEDOM-EV study.”

Slated to yield data in 2014, well before FREEDOM-EV, is the Phase III trial with Allschwil, Switzerland-based Actelion Ltd.’s oral selexipag for PAH, a first-in-class, nonprostanoid IP receptor agonist. The Actelion trial bears a morbidity/mortality endpoint, so success could threaten Orenitram and Tyvaso.