West Coast Editor
Generating still more news in the hot zone of pulmonary arterial hypertension (PAH), United Therapeutics Corp. signed a licensing deal with specialty pharma firm Supernus Pharmaceuticals Inc. for the ongoing development of UT-15C, the former's sustained-released prostacyclin analog.
United Therapeutics' stock (NASDAQ:UTHR) closed Tuesday at $49.34, down 8 cents.
Rockville, Md.-based Supernus gets undisclosed milestones and royalties from United Therapeutics, of Silver Springs, Md., based on the sales of UT-15C, an oral formulation of treprostinil, which is the active ingredient in UTC's FDA-approved Remodulin for subcutaneous and intravenous treatment of PAH.
"They're giving us access to the technology necessary to formulate the tablets," said Fred Hadeed, vice president of business development and chief financial officer for UTC.
Commercial scale-up activities for UT-15C are ongoing, and UTC recently kicked off late-stage studies in PAH. The Phase III program is slated to include 50 centers, with patients getting Remodulin twice daily, as a monotherapy (150 patients) and as an add-on therapy (300 patients).
Judging the likely success is tricky given the lack of published results.
"The program has progressed very quickly, and that's why you've not seen a lot of data," Hadeed noted.
But the dream of an oral PAH drug with strong efficacy - one that could be used with other, oral PAH compounds, much the way HIV drugs are given in combination - leads observers to throw around popular phrases such as "holy grail" and "hallmark event."
PAH patients "have multiple things wrong with them, and each of the various orals available now work on different aspects of the disease," Hadeed said, and declined to estimate when the Phase III trials will finish.
"We just started enrolling [this month]," and fewer than half a dozen patients are on board, he said.
There's an inhaled version of treprostinil, too, and UTC said Monday that the FDA gave its nod to expansion of the ongoing TRIUMPH study under way by Lung Rx Inc., UTC's wholly owned subsidiary. Specifically, the agency will let into the study Class III and IV patients who get Revatio as monotherapy. Enrollment had been limited to those getting Tracleer as monotherapy.
"It's a minor change to the trial, but one we're happy about," Hadeed said.
Tracleer (bosentan), the PAH drug that generates the most revenue, is Allschwil, Switzerland-based Actelion Ltd.'s approved endothelin agonist, cleared in Europe four years ago and approved in the U.S. in November 2001. Revatio, from New York-based Pfizer Inc., is a lower-dose form of sildenafil citrate (the active ingredient in the erectile-dysfunction drug Viagra), and was approved for PAH a year ago.
The FDA also agreed to allow 200 evaluable patients into the Lung Rx's 12-week TRIUMPH trial (the number had been 150), with an interim analysis slated after 150 have finished.
Inhaled combinations have worked before. Tracleer with inhaled Ventavis (iloprost) from CoTherix Inc., of South San Francisco, yielded positive results in the six-minute walk test over Tracleer alone in a 65-patient Phase II study called STEP. Data were disclosed during the November meeting of the American College of Chest Physicians in Montreal.
Many researchers believe adding a PDE5 inhibitor such as sildenafil to a prostacyclin will confer even more advantage than Tracleer with a prostacyclin.
Meanwhile, UTC is hammering away at its core business, going after the market for the I.V. form of Remodulin as the firm tries to persuade physicians to give up Flolan (epoprostenol sodium), the PAH therapy from London-based GlaxoSmithKline plc. It's an important effort, since Revatio steadily is picking up patients who've failed Tracleer, and Ventavis is doing the same. The money's in Flolan conversion.
Coming up fast in PAH is ambrisentan from Denver-based Myogen Inc., a non-sulfonamide, propanoic acid-class, type-A selective endothelin receptor antagonist in Phase III trials. Top-line data in December showed the drug improved patients' exercise capacity, as well as a key secondary endpoint of time to clinical worsening. (See BioWorld Today, Dec. 13, 2005.)
Earlier this month, Encysive Pharmaceuticals Inc., of Houston, said regulators in Europe recommended approval there of Thelin (sitaxentan), the oral endothelin blocker. In March, the FDA told Encysive that the drug is approvable in the U.S., but more trials must be done. (See BioWorld Today, March 28, 2006, and June 5, 2006.)