In early August, Triangle Pharmaceuticals Inc.'s stock shot up surrounding favorable interim data from a Phase III trial of the company's lead product candidate for HIV. And Thursday, the stock was up again when Triangle said it had taken the positive data and filed its first new drug application.
Triangle's stock (NASDAQ:VIRS) closed Thursday at $3.86, up 37 cents, or 10.6 percent. By comparison, the stock closed at $2.88, up 53 cents, after release of the positive interim data for the HIV drug called Coviracil. (See BioWorld Today, Aug. 1, 2002.)
Coviracil (emtricitabine) is a nucleoside reverse transcriptase inhibitor licensed from Emory University in Atlanta.
"What's different about Coviracil is its versatility, its potency, the fact that it's a true once-a-day nucleoside," Daniel Welch, Triangle's chairman and CEO, told BioWorld Today. "It's been proven in a number of regimens to be very competitive in terms of efficacy, safety and patient convenience, so what makes it unique is that it's kind of all in one."
Triangle, of Durham, N.C., expects to be notified later this year in reference to its request for fast-track status. The standard FDA approval process could take up to a year.
"We think Coviracil will be a very important agent in the treatment of HIV disease," Welch said. "It will be our first compound on the market and it also will fund the development of our subsequent programs, namely amdoxovir and clevudine for HIV and the hepatitis B virus, respectively, as well as Coviracil for HBV. So, it will be our first product, a significant product, and it will be the engine, the fuel for the development and marketing of the next wave - so it is huge for us."
The Coviracil application includes data from about 2,300 patients who participated in three trials known as FTC 301, 302 and 303.
FTC 301, a 48-week Phase III trial of 571 patients, compared once-a-day Coviracil to Zerit (stavudine) given twice daily. Each drug was combined within a background regimen of Sustiva (efavirenz) and Videx EC (didanosine). According to the company's analysis, 87 percent of the patients on once-a-day Coviracil showed persistent virologic response through six months compared to 80 percent of the twice-daily Zerit patients. Coviracil patients also had significant improvements in immunologic function.
Supporting data from trials 302 and 303 also have been submitted as part of the new drug application. Triangle has had a little trouble with FTC-302 in the last couple of years. (See BioWorld Today, Aug. 8, 2001, and April 7, 2000.)
A little more than a year ago, the company had to cut its staff by 35 percent after the FDA indicated that data from FTC-302 would not be enough to secure drug approval. And before that, in April 2000, the South African Medicine Council recommended that Triangle stop FTC-302 because of concerns with liver toxicity. The company didn't. Instead it forged ahead without increasing enrollment. The 468 patients who were already enrolled continued receiving Coviracil.
And there's still another twist to the Coviracil story. Since 1999, Triangle has been working with Abbott Laboratories, of Abbott Park, Ill., to develop the product. But in August - on the same day that Triangle released the promising Phase III data - Abbott terminated its $335 million collaboration with Triangle to develop Coviracil and two other products. (See BioWorld Today, June 4, 1999.)
Citing diverging interests, Abbott dropped the deal in favor of focusing on a third-generation protease inhibitor and potential breakthrough drugs in the hepatitis C area.
But Abbott certainly didn't leave Triangle empty-handed. The larger company agreed to supply the launch inventory of Coviracil and to make its Chicago manufacturing facility available for up to 36 months should Triangle need support. Upon U.S. approval of Coviracil for HIV, Abbott has agreed to provide Triangle with an unsecured credit line of $30 million, and on European approval, $12.5 million will be made available.
Abbott will receive a 1 percent royalty on the first $200 million cumulative sales of Coviracil for HIV.
Meanwhile, Triangle received rights to Coviracil in hepatitis B, currently the subject of a Phase III trial, and all rights to amdoxovir (Phase II) for HIV and clevudine (Phase I/II) for HBV.