By Mary Welch
Texas Biotechnology Corp. and SmithKline Beecham plc won FDA approval of argatroban (formerly known as Novastan), an anticoagulant for the prevention or treatment of thrombosis associated with heparin-induced thrombocytopenia (HIT).
"We are just thrilled," said David McWilliams, president and CEO of Texas Biotechnology. "From our perspective, the FDA looked at this drug and understood its significance. It can help patients with this dreadful, devastating disease. Once you've seen a patient with HIT, you never want to see another one. SmithKline will go on an education program, and you'll be seeing the drug used effectively to help reduce death."
"This certainly is an underserved disease and now there is a fairly good treatment for it," said Albert Rauch, senior vice president and biotech analyst with First Union Securities in New York. "The disease can get pretty ugly. We see the potential market for this indication as more than $600 million."
HIT is an allergic reaction caused by heparin, a common anticoagulant used to prevent blood clots. If left untreated or misdiagnosed, HIT patients may develop serious complications such as pulmonary embolism (blood clot in the lungs), heart attack, limb damage requiring amputation, or even death. Mortality from HIT is estimated to be as high as 30 percent in patients who develop serious complications.
More than 12 million Americans are treated with heparin for conditions such as blood clots in the legs or lungs, or heart attacks each year. Of those 12 million, as many as 360,000 will develop HIT. Of those, an estimated 120,000 will develop a thrombotic complication, such as stroke, limb amputation or death, and up to 36,000 people die.
The approval prompted a $7 million milestone to Texas Biotechnology from London-based SmithKline Beecham. The total value of the companies' partnership is about $30 million, McWilliams said. However, at the time of the deal's signing, it was promoted as being worth more than $75 million. (See BioWorld Today, Aug. 7, 1997, p. 1.)
Argatroban is the product's generic name. The FDA did not support Novastan as its brand name, so the product is awaiting the FDA's approval of a new name.
Argatroban is a synthetic small-molecule inhibitor of thrombin, an enzyme involved in blood clotting. It does not produce the antibodies that heparin does. Heparin is the most commonly administered anticoagulant on the market, with about 10 million people receiving the drug each year.
The path toward approval was rocky. The Houston-based company submitted a new drug application (NDA) in 1997 but it failed to get FDA approval. At the time, McWilliams called the setback a "little hiccup along the road for Novastan." (See BioWorld Today, May 12, 1998, p. 1.)
The NDA was resubmitted with new historical data on 193 patients, about the same number as in the original trial. In addition, a Phase III trial that was ongoing at the time of the original NDA submission was completed, and that data was included in the refiling. In total, some 564 patients were given argatroban in two Phase III trials. (See BioWorld Today, March 23, 1999, p. 1.)
"It just shows that perseverance pays off," Rauch said.
McWilliams agreed. "Granted, we didn't do it in the smoothest of fashions. But no matter how you get there, getting there is the point. Tenacity is 99 percent of the biotechnology business, I'm convinced."
The company's partner is "now ready to go forward and market the product," McWilliams said. "They are standing right next to us and we feel very good about handing the ball off to them so they can go build a market. They are still saying it'll be launched in the third quarter."
Texas Biotechnology licensed U.S. and Canadian rights to the drug, which is derived from an amino acid called L-arginine, from Genentech Inc., of South San Francisco.
Phase III trials have been completed for the use of the drug in HIT patients undergoing angioplasty, and Texas Biotechnology is looking at developing it as an alternative to heparin in hemodialysis, stroke and acute coronary syndrome.
The company's stock (AMEX:TXB) closed on Friday at $19.06, down 12 cents.