By Randall Osborne
After analyzing data 20 weeks into its Phase II/III study, Gilead Sciences Inc. said it expects to use data from that trial and others of Preveon (adefovir dipivoxil), a reverse transcriptase inhibitor, as the clinical support for a new drug application to the FDA.
Gilead, of Foster City, Calif., also made public results from a Phase II trial of adefovir dipivoxil against hepatitis B, showing the drug reduced blood levels of the virus almost to zero.
The interim analysis of data involving the first 85 patients from the Preveon study in HIV patients, known as GS 411, showed that once-daily treatment with the drug combined with other anti-HIV agents led to improvements. It reduced HIV RNA and increased CD4 cell counts in numbers similar to those seen in a standard-of-care control group.
Patients in the randomized, open-label, controlled trial had not previously received antiretroviral therapy. Each trial patient was assigned to one of four Preveon regimens combining 120 milligrams of the drug once per day with a protease inhibitor (indinavir), plus one or two of the reverse transcriptase inhibitors zidovudine (AZT), lamivudine (3TC) or stavudine (d4T). AZT and 3TC are marketed by Glaxo Wellcome plc, of London, and d4T is sold by Bristol-Myers Squibb Co., of New York. Indinavir is sold by Merck & Co. Inc., of Whitehouse Station, N.J.
Those in the control group received the standard-of-care triple combination regimen of AZT, 3TC and indinavir, referred to as the "gold standard" of treatment for HIV.
At 20 weeks, about 80 percent of patients treated with one of the Preveon regimens — like those in the control group — achieved undetectable levels of HIV RNA and showed median decreases similar to those in the control group.
"We looked at very specific combinations," said Lana Lauher, spokeswoman for Gilead. "The triple combination arms with Preveon looked comparable to the gold standard."
Another Phase II/III trial, known as GS 408, studied Preveon in heavily pre-treated patients, with positive results.
"We showed a clear-cut advantage to adding Preveon on top of anything else the patient is taking," Lauher said.
Preliminary data from the Preveon trial will be presented Friday at the 11th International Conference on Antiviral Research in San Diego. More trials are under way.
"There are more than 10 ongoing studies," Lauher said. "We would anticipate [the NDA filing] will include data from GS 408 and GS 411, with data from some of the other trials."
In the hepatitis B trial, the first of three dose cohorts was given 30 milligrams of adefovir dipivoxil once per day for 12 weeks. The drug reduced the amount of the virus DNA to undetectable levels in the majority of patients, with an overall median decrease of 99.7 percent.
Based on the data, Gilead is designing a program of Phase III studies in hepatitis B.
"The other two dose cohorts are fully enrolled, but we don't have the data analyses yet," Lauher said. "But these data are strong enough to tell us what we need to know to design the Phase III program, and we're moving as quickly as we can to start the studies this year."
Gilead's stock (NASDAQ:GILD) closed Wednesday at $42.625, down $0.25. *