Special To BioWorld Today
Gilead Sciences Inc. said its antiviral drug - the reverse transcriptase inhibitor Preveon (adefovir dipivoxil), which hasproven effective against HIV - reduces levels of the hepatitis B virus (HBV) in chronically infected patients.
Gilead Sciences Inc. reported favorable results in a Phase II trial of adefovir dipivoxil for hepatitis B. Phase III trials are expected to begin early next year. Separately, the company expects to file a new drug application for the company's HIV drug, Preveon, in the first half of 1999, said Sheryl Meredith, spokeswoman for Foster City, Calif.-based Gilead.This will be based on the pivotal study GS 408. Complementary studies in HIV were GS 417 and GS 420.
Gilead reported data from one Phase II study with 53 patients and another with 14.
In the first study, 53 patients with elevated levels of alanine aminotransferase (ALT), were given 5 mg of adefovir dipivoxil, 30mg, 60 mg or placebo. The virus could not be detected by branched chain DNA assay in 10 of the 15 patients who received 30mg. With polymerase chain reaction analysis, median reduction was shown to be 99.99 percent. Similar results were seen in the60 mg dose.
After 24 weeks, eight of the 30 patients in the two higher-dose arms had lost HB "e" antigen and six of 30 seroconverted. Nopatients on placebo seroconverted or lost HB "e" or surface antigen.
The smaller Phase II study was in patients with chronic HBV and normal ALT level. HBV DNA was reduced significantly in thetreated arm vs. placebo.
Meredith said the Phase III study of adefovir dipivoxil for HBV likely will look at 10 mg and 30 mg doses vs. placebo over 48weeks of treatment and one year of follow-up. It will be a multinational pivotal trial, she said. Adefovir dipivoxil, a nucleotideanalogue, is the same drug as Preveon, which is being tested against HIV, but will have a different name when used againstHBV.
The time frame for the NDA was pushed back a little because Gilead wants to include results of two studies that will give moreinformation on the 60 mg dose, Meredith said, and the drug is unpartnered for both indications. For now, Gilead is focusing onfinding a partner to co-market it in the HBV indication, Meredith said.
Trial investigator Jenny Heathcote, professor of medicine at the University of Toronto, said in a statement that the resultsrepresented a breakthrough in treating hepatitis B. "The data show that, in patients with chronic hepatitis B, adefovir dipivoxilcan rapidly reduce levels of multiplying virus in the bloodstream from several billion copies to just a few hundred in a matter ofweeks," she said.
"We were very pleased," Heathcote added, "to see that adefovir dipivoxil was equally effective at suppressing viral loadamong patients with normal and elevated ALT levels. The absence of seroconversion in the normal ALT group was notsurprising, given the short treatment course."
Glaxo Wellcome plc, of London, and BioChem Pharma Inc., of Laval, Quebec, developed the antiviral agent Epivir(lamivudine), which also targets HBV. The FDA's Antiviral Drugs Advisory Committee in October recommended approval ofthe drug for treating chronic hepatitis B in adults. That drug, a nucleoside reverse transcriptase inhibitor, already is approved fortreating HIV under the name 3TC.
Gilead presented its data in Chicago at the meeting of the American Association for the Study of Liver Disease. The company'sstock (NASDAQ:GILD) closed Monday at $30.843, down $0.781.