By Karen Pihl-Carey

It took a little more than two years, but the sky finally looks clear for Novastan now that the FDA issued an approvable letter to Texas Biotechnology Corp.

The Houston-based company received the letter late Friday and disclosed it Tuesday, this time with better news than it received in May 1998 when the FDA issued a "not approvable" letter for the drug. Novastan is an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT).

"The news is really good in terms of the approvable letter. Equally exciting, or actually more exciting probably, is the fact that ... the proposed label from the FDA is quite broad and really reflects their confidence in Novastan," said David McWilliams, president and CEO of Texas Biotechnology. "So the news is not only good, it's actually better than we expected. And after a long steep climb, it feels really good to have the FDA validate the therapeutic value of Novastan."

McWilliams said in a conference call Tuesday that company officials still are working on the pricing of Novastan, adding that a competitor, Refludan, marketed by Aventis Pharmaceuticals Inc., of Frankfurt, Germany, runs about $600 a day. He said the company is preparing for commercial-scale manufacturing and that medical education activities are continuing.

In a research report, Elise Wang, first vice president of New York-based PaineWebber Inc., said the FDA's decision to include prophylaxis, or prevention, therapy in the label for Novastan was an "upside surprise" that "highlights the compelling safety and easy-to-use profile" for the drug.

Because of the expanded label, she said pricing for the product might be more than double the original estimation of $200 per dose. "With approximately 300,000 to 400,000 U.S. patients suffering from HIT each year, we estimate a multi-$100 million dollar to $1 billion dollar market opportunity."

Final approval of the drug is expected within 60 days. Texas Biotechnology must agree or amend the FDA's proposed labels, as well as agree to two Phase IV studies before final approval can be granted.

"The bulk of what we have to do in the next 30 to 60 days is to amend the label," said Pam Murphy, the company's vice president of corporate communications.

SmithKline Beecham plc, of London, has rights to market and co-develop Novastan in the U.S. and Canada, according to an August 1997 agreement. SmithKline also has marketing rights to all other indications of the drug. (See BioWorld Today, Aug. 7, 1997, p. 1.)

"We have submitted the Canadian NDA and have gotten priority review," McWilliams said. "So we would anticipate an approval in Canada sometime this year."

Texas Biotechnology also expects to submit a supplemental NDA soon for patients who have HIT and plan to undergo angioplasty, McWilliams said. Other future indications of the drug could include treating HIT patients undergoing hemodialysis, as well as patients who suffer from acute ischemic stroke. The drug is marketed in Japan for the last indication.

"It's a very easy to use drug. It's very predictable," McWilliams said. "So we think there is good potential."

Novastan (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. Of the 10 million, about 300,000 to 400,000 patients develop HIT, an allergic reaction that causes an abnormal reduction in blood platelet levels.

"In effect, you have a coagulation phenomenon occurring in a situation where you're trying to prevent that," McWilliams said. "And this has severe consequences," including blood clots, amputation and death.

With the label recommended by the FDA, Novastan could treat patients who are high-risk, McWilliams said. According to studies, he said, about 15 percent of patients who undergo orthopedic surgery form the antibodies to heparin, and a third of those patients will get HIT. Also, about 50 percent of bypass surgery patients form the antibodies to heparin, and about 10 percent will get HIT, McWilliams said.

"As these studies are developed this will enhance the use of the drug over time," he said.

Novastan's researchers will present the drug's Phase III trial results at the American College of Cardiology meeting in March.

Texas Biotechnology decided to resubmit an NDA for Novastan in March 1999 using historical data after the FDA issued a not approvable letter of the drug almost a year earlier. The company would not discuss details of that letter. (See BioWorld Today, May 12, 1998, p. 1; and March 23, 1999, p. 3.)

Behind Novastan, Texas Biotechnology has two compounds in Phase II development. Sitaxsentan (TBC11251), an endothelin receptor antagonist, is being developed to treat pulmonary arterial hypertension and chronic heart failure. And TBC1269 is a selectin antagonist being developed for asthma.

The company's stock (AMEX:TXB) closed Tuesday at $13.75, down $1.25.