By Karen Pihl-Carey

Gilead Sciences Inc. began enrolling patients in a pivotal trial of tenofovir disoproxil fumarate to treat HIV infection.

The double-blind trial will be the first of several that could support registration. It will enroll 600 patients at nearly 70 sites in the U.S., Europe and Australia.

Tenofovir is a nucleotide analogue taken once a day in a pill form as part of combination antiretroviral regimens.

"We've seen strong antiviral activity as both a model therapy and now in combination therapy that appears to be durable," said Mark Perry, Gilead's chief financial officer and senior vice president. "And we have not identified any significant safety problems with the drug to date. So far so good."

The Phase III randomized study will last 48 weeks and will evaluate the safety and antiviral activity of tenofovir in combination antiretroviral regimens in treatment-experienced patients. Perry told BioWorld Today the company expects to conduct a pivotal trial in treatment-naove patients as well.

"We expect to launch another one, possibly two, additional studies in three to six months," he said.

Treatment-experienced patients enrolled in the study must have HIV RNA levels greater than or equal to 400 copies/mL and less than or equal to 10,000 copies/mL. They also must have maintained a stable antiretroviral regimen for at least eight weeks prior to enrollment. The regimen must not consist of more than three antiretroviral agents.

Patients will be divided into two groups, with some receiving a 300 mg dose of tenofovir and others receiving a placebo, in addition to their existing regimens. They will maintain their antiretroviral regimen for 24 weeks of blinded dosing, then patients receiving tenofovir will have the option to change their therapy and those receiving placebo will cross over to open-label active tenofovir for the remaining 24 weeks.

"We hope to have the data to file with the FDA for approval sometime in the first half of 2001," Perry said.

Gilead presented positive clinical results of tenofovir in September at the 39th Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco. Data showed a 300 mg dose of the drug reduced circulating virus in the bloodstream by more than 80 percent. (See BioWorld Today, Sept. 28, 1999, p. 1.)

An FDA advisory panel refused in November to endorse Gilead's HIV drug, Preveon (adefovir dipivoxil), based on its kidney toxicity and questions about its effectiveness. At the time, analysts said it was unlikely the company would move forward with another trial of Preveon, as tenofovir eventually would cannibalize it. (See BioWorld Today, Nov. 3, 1999, p. 1.)