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United Therapeutics scraps drug after late-stage miss

  • An experimental drug for a rare lung condition has failed in a registrational trial, prompting its manufacturer, United Therapeutics, to halt further development.
  • United has been testing a combination of the drug, called esuberaprost, and its marketed product Tyvaso in the Phase 3 BEAT study, which enrolled patients with pulmonary arterial hypertension who were having sub-par responses on Tyvaso. Esuberaprost and the active ingredient in Tyvaso, treprostinil, are both blood vessel dilators that hold “complementary pharmacokinetic and pharmacodynamic profiles,” according to United.
  • Though few details were given in a Monday statement, the company did say the study failed to meet its primary endpoint of delayed time to first clinical worsening event.

Patients with pulmonary arterial hypertension, or PAH, have high blood pressure in the arteries of their lungs. United’s business relies almost entirely on treating the disease, with 95% of its net product sales coming from four PAH therapies.

Lately, those sales have been weakening. They fell about 6% last year, largely because Mylan launched stateside a generic version of Adcirca (tadalafil), an Eli Lilly drug to which United has U.S. commercial rights for the treatment of PAH.

United noted in its most recent annual filing that during the four months from when the generic launched until December 2018, the average number of Adcirca bottles sold to distributors decreased more than 55% compared to the same period a year prior.

A copycat of the company’s top-selling product, Remodulin (treprostinil), has already come to market in the U.S. and Austria. Further generic competition is expected to hit the U.S. and Europe sometime this year.

United has claimed label expansions and new products could bring a return to growth as soon as next year. Among those potential products, company leadership seemed especially bullish on esuberaprost, with CEO Martine Rothblatt noting on a recent earnings call that it is “one of the most exciting drugs that we will ever launch.”

The idea there was that esuberaprost, an oral analogue of the vasodilator prostacyclin, would expand the market opportunities for Tyvaso (treprostinil), an inhaled prostacyclin analogue. United predicted that a positive readout from the BEAT study would allow it to file for approval the combo of esuberaprost and treprostinil​, dubbed Tysuberprost, within the following three months and launch commercially in 2020.

If successful, BEAT would “significantly lengthen the period of time our patients are able to use Tyvaso,” Rothblatt said on the earnings call. “We expect that this could grow our Tyvaso patients to between 5,000 and 10,000 cases.”

The trial was not successful, however, and derails United’s plans for esuberaprost.

Investment bank Jefferies put little value in Tysuberprost, noting that if the combo gained approval it would just “push out” use of Remodulin and Orenitram, another United drug with treprostinil as its active ingredient. Analyst Eun Yang wrote in an April 8 note to investors that the company’s bigger problem is a pipeline that lacks diversity outside of PAH.

United shares were down nearly 3% to $117.45 apiece at market’s open Monday, though they dropped lower in late-morning trading.