Washington Editor

GlaxoSmithKline plc has agreed to pay Gilead Sciences Inc. upward of $40 million for the Asian and Latin American rights to Gilead’s hepatitis B drug, adefovir dipivoxil.

The product, which has not been assigned a trade name, is a nucleotide analogue that works by blocking the hepatitis B virus DNA polymerase, an enzyme responsible for replicating the virus. Adefovir dipivoxil is a once-daily oral drug.

About a month ago, Foster City, Calif.-based Gilead filed a six-month priority review application with the FDA for chronically ill patients who are treatment-na ve or experienced. One analyst said he expects U.S. approval by the end of the year, with sales topping $142 million by 2006. (See BioWorld Today, March 25, 2002.)

Under terms of the deal with GSK, of London, Gilead will retain rights in the U.S., Canada, Eastern and Western Europe, Australia and New Zealand.

But GSK will market the drug in areas of the world that experience a higher incidence of HVB, including China.

“We wanted to partner adefovir dipivoxil in other parts of the world because we don’t currently have infrastructure in Asia and that’s a very important market for hepatitis B,” Amy Flood, Gilead’s manager, communications, told BioWorld Today. “GSK has already started building the market for lamivudine [3TC], so they have expertise not only in that part of the world, but also in this therapeutic area. So that makes them an ideal partner.”

Financial terms of the licensing agreement require GSK to pay Gilead a $10 million up-front fee and additional cash payments up to $30 million upon achievement of certain milestones. Furthermore, GSK will pay Gilead an undisclosed royalty on net sales, and has accepted full responsibility for development and commercialization in the territories covered by the agreement.

Gilead has filed for approval only in the U.S. and Europe.

The company initiated Phase I studies in China and has agreed to transition those trials to GSK, which will be responsible for Phase II/III in that part of the world, Flood said.

Flood said GSK has not specified timelines for trials or regulatory approval. Representatives of GSK could not be reached for comment.

But in a prepared statement, Howard Pien, president, Pharmaceuticals International, GlaxoSmithKline, said, “Adefovir dipivoxil will be a valuable addition to our portfolio. Our experience of working with hepatologists over many years, first with vaccines and more recently with lamivudine, confirms that this is a complex disease. We hope adefovir dipivoxil will offer a valuable new treatment option to physicians and will help improve the quality and duration of life of millions of hepatitis B patients across Asia, Latin America and other international areas.”

Aside from lamivudine, adefovir dipivoxil will compete with Madison, N.J.-based Schering-Plough Corp.’s Intron A (interferon alpha). While patients using lamivudine tend to quickly develop resistance, Intron A commonly has difficult-to-tolerate toxicities and works in a low number of patients, Flood said.

In China, Korea, Japan and Taiwan, GSK intends to develop adefovir dipivoxil for patients with chronic hepatitis B who are na ve, as well as for those who have developed resistance to lamivudine.

Gilead’s new drug application is supported by data from Phase III studies in hepatitis B “e” antigen-positive patients, hepatitis B “e” antigen-negative patients and chronic hepatitis B patients with lamivudine-resistant HBV.

Data from a 515-patient trial (Study 437) indicated that adefovir dipivoxil in na ve chronic hepatitis B patients showed no resistance mutations. The trial met its endpoints of liver histology improvement and showed no kidney toxicity. Also, seroconversion was observed in 12 percent of patients treated with 10 mg for 48 weeks compared to 6 percent of patients on placebo. (See BioWorld Today, June 25, 2001.)

In another trial (Study 438), Gilead evaluated 185 patients and determined that treatment with a 10-mg once-daily dose for 48 weeks was associated with improvements in liver histology in 64 percent of patients who received the drug compared to 33 percent of patients who received placebo. (See BioWorld Today, Sept. 20, 2001.)

At one time, Gilead was studying adefovir dipivoxil for HIV but abandoned the plan after an FDA advisory panel voted against the product for that indication. (See BioWorld Today, Nov. 3, 1999.)

Despite that failure, last fall the company ended up winning FDA approval for another HIV drug, Viread (tenofovir disoproxil fumarate), a nucleotide analogue reverse transcriptase inhibitor. The once-daily drug was launched in the U.S. in October and Europe in February.

Gilead’s other marketed products are AmBisome, for systemic fungal infections; Tamiflu, for influenza; Dauno-Xome, for HIV-associated Kaposi’s sarcoma; and Vistide, for AIDS-related cytomegalovirus.

GSK markets lamivudine as Zeffix and under other names in 50 countries worldwide.

Gilead’s stock (NASDAQ:GILD) closed Monday at $29.13, up 9 cents.