United Therapeutics' oral treprostinil fails to meet goal of Phase III trial

United Therapeutics announced Wednesday that a late-stage trial of oral treprostinil in patients with pulmonary arterial hypertension (PAH) failed to meet its primary endpoint. Shares in the company, which markets injectable and inhalable versions of the drug in this indication under the names Remodulin and Tyvaso, respectively, fell as much as 22 percent on the news.

The FREEDOM-C(2) trial randomised 310 patients with PAH who were optimised on an endothelin receptor antagonist, a phosphodiesterase-5 inhibitor or both, to receive oral treprostinil or placebo twice daily. Mean six-minute walking distance was approximately 333 metres at study onset. After 16 weeks, the placebo-corrected median change in walking distance was 10 metres for those who received treprostinil, which was not considered statistically significant. A preliminary analysis of other secondary endpoints, including time to clinical worsening and PAH signs and symptoms, did not differ significantly between patients in the treprostinil and placebo arms. The drugmaker noted that further analysis of the results is ongoing, with full data to be presented at an upcoming medical meeting.

Commenting on the results, J.P. Morgan analyst Geoff Meacham said the "news comes as a surprise, where we and most on the Street were at least expecting a six-minute walk distance benefit that was statistically significant and in the 12-15 metre range." United Therapeutics COO Roger Jeffs noted that one issue in the study was that patients who received placebo showed a surprising improvement in walking distance, making comparisons with treprostinil harder. He added that the trial may also have been skewed toward poor responders, since people who have responded well to treatment would be less inclined to join. "We may be selecting a less responsive group of patients," Jeffs remarked.

The company reported that the discontinuation rate among patients treated with the oral drug in the trial was 11 percent, most often due to headache, nausea and vomiting, compared with 3 percent for those who took placebo.

Jeffs said "while we did not achieve a statistically significant result for this trial, we believe the positive results from our previously-announced FREEDOM-M study support [an FDA] filing of oral treprostinil in treatment naive patients." He added that the company plans to file for approval with US regulators "by the first half of 2012."

While Deutsche Bank analysts said "we believe it will be very difficult" for the drug to garner approval, ISI Group analyst Mark Schoenebaum noted that "we think odds of approval on one trial are low, but not remote." He suggested that the FDA might accept pooled clinical data from trials of treprostinil, or that another study could be conducted.

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