The failure of Tracleer to meet primary endpoints in a Phase III trial of chronic heart failure patients could be a blessing in disguise for Switzerland-based Actelion Ltd.
If Tracleer (bosentan) produced positive results in that Phase III trial, called ENABLE, Actelion’s partner, South San Francisco-based Genentech Inc., would have had the right to exercise its option to co-promote the product, therefore cutting into Actelion’s revenues and profits from the sales for the first approved indication.
Actelion, of Allschwil, and Genentech signed a deal potentially worth $140 million two years ago to develop and co-promote Tracleer, an endothelin receptor antagonist. Actelion was scheduled to receive a $35 million up-front payment as part of the deal. (See BioWorld Today, Dec. 14, 2000.)
When Actelion won FDA approval in November to sell Tracleer in pulmonary arterial hypertension (PAH) patients, Genentech was on its way to making money off the deal. (See BioWorld Today, Nov. 26, 2001.)
But Thursday’s announcement slows the process.
From a financial standpoint for Actelion, though, the news isn’t that bad, said Roland Haefeli, Actelion’s vice president of corporate communications.
Actelion’s stock (SWX:ATLN) closed Thursday at SFr63.70, down just 1.2 percent.
“There are two sides to the coin of what this means to Actelion,” Haefeli said. “There is the side that it does not work in chronic heart failure (CHF) and this is definitely not the preferred outcome. The other side is the economic aspect. Actelion will be able to continue to solely market and retain revenues and profits from Tracleer in PAH.”
Tracleer, an orphan drug for PAH, costs $28,500 per patient per year. There are about 50,000 potential patients in the U.S., Haefeli said. (Previous company estimates said there were upwards of 100,000 U.S. patients.)
“Compare that to the potential pricing of CHF,” Haefeli said. “A lot of people think the drug would be priced at levels currently in the market $2,000, $3,000 or $4,000. People are very much afraid that if the drug is only a little bit effective in CHF, then it would not make sense to introduce it to the market at a low price when we have to share the profits with Genentech.”
That is, if Genentech were to exercise its option.
“While we cannot exercise the option at this time, we certainly can explore other opportunities under our current agreement with Actelion,” Shelley Schneiderman, Genentech’s manager of corporate communications, told BioWorld Today.
Tracleer is the subject of other ongoing clinical trials, Haefeli said. In one, it is being studied with Flolan (GlaxoSmithKline plc) for PAH, and in another, Tracleer is being tested on children with congenital heart disease. Also, there are ongoing tests and pilot studies in AIDS-related illnesses.
Haefeli said Actelion expects to release more information about future indications at the American College of Cardiology meeting in Atlanta March 17-21.
At that time, Actelion likely will have complete data on the failed Phase III trials, referred to as ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure), Haefeli said.
The double-blind, placebo-controlled, multicenter trial included 1,613 patients who were randomized to ENABLE-I and ENABLE-II.
The endpoints were risk reduction in time to death or hospitalization due to CHF, and improvement in clinical status at nine months of treatment. The trial did generate positive long-term data on safety in patients receiving Tracleer for up to 30 months. Specific efficacy results of the study were expected to be released later.
Haefeli said it’s premature to speculate whether Tracleer can be used in CHF subpopulations. And, he said he’s not sure whether the company will conduct other Phase II and Phase III trials in CHF patients.
Actelion has been known to make such a move.
Following mixed results on Phase III trials of Veletri (tezosentan) in acute heart failure patients, Actelion returned to Phase II trials. (See BioWorld Today, March 21, 2001, and April 23, 2001.)
Genentech and Actelion have a deal with Veletri similar to the Tracleer agreement.
Schneiderman said Genentech will have another opportunity co-promote Veletri if new trials end well.