By Frances Bishopp

Hoffmann-La Roche Ltd. has agreed to pay Agouron Pharmaceuticals Inc. and Japan Tobacco Inc. $40 million for the exclusive marketing rights for the anti-HIV drug, Viracept, in Europe and other territories outside North America, Japan and Asia.

Japan Tobacco's pharmaceutical division currently is collaborating with Agouron on the development of Viracept.

The deal also includes royalties on Roche's sales of the HIV protease inhibitor, for which Agouron, of La Jolla, Calif., filed a new drug application in December 1996, which covers both tablet and pediatric powder formulations of Viracept.

Under terms of a letter of intent, Donna Nichols, senior director of corporate communications, told BioWorld Today, Roche will share responsibility for obtaining rapid approval of Viracept in Europe and other countries outside the exclusive marketing territories of Agouron, which include the U.S., Canada and Mexico and the marketing territories of Japan Tobacco, which include Japan and Asia.

Roche will immediately pay a total of $18 million to the two companies, Nichols said, and will pay an additional $22 million when Viracept is approved in Europe.

Viracept is a synthetic chemical compound designed to inhibit HIV protease, an enzyme that plays an essential role in the replication of HIV and is Agouron's first product to face the regulatory approval process.

In July 1996, the company made the decision to complete a stock offering despite a slump in the market to raise funds to keep its Viracept development on course. The company raised $75 million in the sale of 2.5 million shares, but sold the stock for 25 percent less that it was trading when the company registered the offering.

Should Viracept be approved by the FDA, it will join three other protease inhibitors already on the market: Saquinazir, developed by Roche, Ritonavir, developed by Abbott Laboratories, of Abbott Park, Ill. and Indinavir, developed by Merck & Co. Inc., of Whitehouse Station, N.J.

Kevin Tang, an analyst with Alex, Brown & Sons Inc., of New York, told BioWorld Today that for Agouron, the deal "was fantastic."

"When you look at a partnership," he said, "you look at a couple of things: the quality of the partner, the up-front funding and the royalty stream. This is an excellent deal on all three fronts."

"Roche is a major player in the HIV field, the licensing fees are significant and the royalties, although undisclosed specifically, are very significant," Tang said. "Their protease inhibitor has the potential to be a $500 million product."

On Jan. 6, Agouron reported that Viracept (nelfinavir mesylate) would be studied in a large comparative clinical trial conducted by the Terry Beirn Community Programs for Clinical Research on AIDS, a program funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

The clinical endpoint trial will evaluate and compare disease progression or death in HIV-infected people taking either Viracept plus nucleoside analogues (AZT, 3TC, ddI, ddC, d4T), or Norvir (ritonavir) plus nucleoside analogues. Rates of occurrence of adverse events or discontinuation from the study as well as changes in CD4+ T cells and plasma HIV RNA will also be compared between the two treatment groups, which involves approximately 1,300 individuals.

This month, Agouron, after conducting an ongoing study in children, said Viracept would be made available without charge to HIV-infected children 2 to 13 years of age. The drug, the company said, had shown preliminary evidence of safety and tolerability and would be made available in both an oral powder and tablet formulation to the designated children until the drug is approved for marketing in the U.S.

Agouron also is collaborating with Japan Tobacco, which conducts research at its Central Research Institute in Osaka, Japan, in the discovery of drugs for treatment of infections caused by hepatitis C and by herpes viruses.

Agouron and Roche, of Basel, Switzerland, are also collaborating on the development and commercialization of Thymitaq Synthase inhibitor (for cancerous solid tumors) and AG3340, a matrix metallaprotease inhibitor for cancer and arthritis, which recently entered Phase I clinical studies. *