You might say Texas Biotechnology Corp. is taking the bull by the horns.
The Houston-based company plans to reacquire full development and worldwide marketing rights to sitaxsentan, a pulmonary arterial hypertension drug developed by ICOS-Texas Biotechnology LP, a partnership formed with ICOS Corp. Under the joint venture agreement, research, development and marketing costs were to be shared equally, as were profits on any product sales.
Financial terms of the latest transaction, which remain subject to ongoing negotiations that could unwind the partnership, were not disclosed. But Texas Biotechnology is eyeing a long-term gain.
"The real key is for Texas Biotechnology to regain control of its core asset," Texas Biotechnology President and CEO Bruce Given told BioWorld Today. "The limited partnership we had with ICOS split 50 percent of the cost but also 50 percent of the ultimate profit coming out of the partnership, and that's a pretty hefty price to pay. I would much prefer to have total control of an asset that's heading into its final pivotal trial and then on to registration, hopefully."
ICOS-Texas Biotechnology has in its portfolio TBC-3711, a backup compound to treat cardiovascular disease not yet in clinical development. But on its own Texas Biotechnology is clearly focused on sitaxsentan. Its immediate plans include evaluating the small molecule in a second pivotal Phase III study beginning in the second quarter. The FDA signed off on the STRIDE II (sitaxsentan to relieve impaired exercise in pulmonary arterial hypertension) trial, which will include three arms - two doses of the drug as well as placebo.
"The highest dose of sitaxsentan will be 100 mg, which was the effective but lowest dose in the first STRIDE trial," Given said. "We also will have a second sitaxsentan dose of 50 mg, which has not yet been tested in pulmonary hypertension but has the potential to also be effective."
Top-line results of the Phase IIb/III trial for sitaxsentan, designed to block the action of endothelin, were reported in October. Data showed sitaxsentan met its primary endpoint at a higher dose, though a lower dose failed to achieve statistical significance. But the higher dose is more associated with liver abnormalities previously recognized as complications related to the endothelin antagonist class of drugs. The 178-patient trial randomized participants to sitaxsentan 100 mg, sitaxsentan 300 mg or placebo treatment once a day.
The 300-mg dose group met the trial's primary endpoint of change in percent of predicted peak VO2 - a measure of endurance - from baseline to week 12, compared with placebo treatment (7 percent relative improvement). (See BioWorld Today, Oct. 22, 2002.)
The trial's development was an initial focus of the joint venture, formed more than two years ago as a 50-50 limited partnership between Bothell, Wash.-based ICOS and Texas Biotechnology to develop endothelin receptor antagonists, including sitaxsentan, which selectively target the endothelin A receptor. The joint venture deal, which included a $2 million up-front payment to Texas Biotechnology, could be worth up to $55.5 million to the Houston-based firm. (See BioWorld Today, June 7, 2000.)
Texas Biotechnology said it would present more specific details from the trial in May as part of two abstracts at the American Thoracic Society meeting in Seattle.
Should sitaxsentan eventually receive approval, Given said it would be dosed once daily and compete with Tracleer, developed by Allschwil, Switzerland-based Actelion Ltd. and co-promoted by South San Francisco-based Genentech Inc. Actelion in September received an approvable letter from the FDA for Tracleer.
"We also will have data available in Class II pulmonary hypertension and pulmonary hypertension secondary to congenital heart disease, neither of which is contained in Tracleer labeling at the moment," Given said. "There's the possibility that we will have lower liver function abnormalities than Tracleer at the ultimate clinical dose, and we continue to collect compassionate-need patients who have failed Tracleer for either efficacy or safety and have gone on to sitaxsentan and seem to be doing quite well."
Texas Biotechnology's first FDA-approved product, Argatroban, is marketed by London-based GlaxoSmithKline plc to treat heparin-induced thrombocytopenia.
"We are not a company that's new to the drug development, new drug application submission and registration game," Given said. "We're a veteran at that, so we're quite comfortable and confident taking over the sitaxsentan program."
Texas Biotechnology, which ended 2002 with about $67 million in cash, said the reacquisition would change its expenditures and it would provide updated financial guidance this month.
Other pipeline projects include Bimosiamose, a selectin antagonist to treat pediatric asthma being developed through Texas Biotechnology's European subsidiary, Revotar Biopharmaceuticals AG. Another compound, TBC-4746, is a VLA-4 antagonist being developed in partnership with Kenilworth, N.J.-based Schering-Plough Corp. as an oral treatment for adult asthma.
Texas Biotechnology's stock (NASDAQ:TXBI) gained 6 cents Friday to close at $1.30. ICOS's stock (NASDAQ:ICOS) rose 20 cents to close at $24.55.