ROCKVILLE, Maryland-The Food and Drug Administration has approved Viread (tenofovir disoproxil fumarate, Gilead Sciences, Inc.) for the treatment of HIV-1 infection in combination with other antiretroviral agents. Viread, a nucleotide analog, remains in cells longer than other antiretrovirals, which enables a dosage of 300 mg taken once a day in tablet form.
ROCKVILLE, MarylandThe Food and Drug Administration has approved Viread (tenofovir disoproxil fumarate, Gilead Sciences, Inc.) for the treatment of HIV-1 infection in combination with other antiretroviral agents. Viread, a nucleotide analog, remains in cells longer than other antiretrovirals, which enables a dosage of 300 mg taken once a day in tablet form.
Viread’s approval marks the first entry of a nucleotide analog reverse transcriptase inhibitor into the HIV-medication market. Nucleotide analogs are similar to nucleoside analogs and inhibit HIV replication in the same way, by blocking the enzyme reverse transcriptase. The FDA action occurred 6 months after Gilead submitted its new drug application to the FDA.
The drug won marketing approval based on data the FDA reviewed from two clinical studies submitted by the sponsor that involved more than 700 patients. One was a 24-week, phase III, placebo-controlled trial; the other was a 48-week controlled dose-ranging trial.
"Patients who received Viread showed significant decreases in the quantities of HIV RNA in their blood, compared to patients who received a placebo with the standard antiretroviral regimen," the FDA said in announcing the approval.
Both clinical trials enrolled patients previously treated with antiretroviral drugs. As a result, the risk-benefit ratio for patients who have not had antiretroviral therapy remains unknown.
Gilead said that an ongoing clinical trial is evaluating Viread in 601 treatment-naïve HIV patients who will receive the drug for 96 weeks in combination with lamivudine (Epivir) and efavirenz (Sustiva). Controls will receive stavudine (Zerit), lamivudine, and efavirenz. Safety and efficacy data for the first 48 weeks of the trial will become available in the first half of 2002.
The FDA noted that there are no Viread study results to show a long-term inhibition of HIV progression.
"The drug has demonstrated a significant antiviral response even in patients who may no longer respond well to available therapies due to the development of viral resistance," said Calvin Cohen, MD, research director, Community Research Initiative of New England and Harvard Vanguard Medical Associates. "There has been a great deal of progress in the fight against HIV, but we still urgently need new treatments. Viread is an important new option because it is powerful and convenient."
Phase III Results
According to Gilead, Viread reduced the level of circulating HIV by 75% among treated patients in the 552-person phase III trial. Treated patients received Viread plus their existing anti-retroviral regimen; the control group received their usual HIV medications and a placebo. "Resistance to Viread is rare and slow to develop," the company said.
The safety data submitted to FDA included results based on two studies that included 653 patients, 443 of them treated with 300 mg of Viread daily for 24 weeks, followed by extended treatment with the drug.
The most common adverse reactions to the drug were mild to moderate gastrointestinal problems, which included nausea, diarrhea, vomiting, and flatulence. However, both the FDA and the company noted that potentially fatal cases of lactic acidosis and hepatomegaly with steatosis have occurred among patients treated with nucleoside analogs, alone or in combination with antiretroviral drugs.