Gilead Announces Data from Landmark Three-Year Clinical Trial of Viread; 144-Week Data Highlight Viread Efficacy, Safety and Side Effect Profile
FOSTER CITY, Calif.--(BUSINESS WIRE)--Feb. 4, 2004--Gilead Sciences, Inc. (Nasdaq:GILD) today announced preliminary three-year (144-week) data from a double-blind Phase III clinical trial (Study 903) suggesting that Viread(R) (tenofovir disoproxil fumarate) is associated with similar levels of viral load suppression and a similar renal safety profile when compared to treatment with stavudine (d4T). At 144 weeks, treatment with stavudine was associated with greater elevations in fasting triglyceride and cholesterol levels and a notably higher incidence of investigator-defined lipodystrophy compared to treatment with Viread. These findings further extend the data from the 48- and 96-week analyses. The company anticipates presenting full data from this study at a scientific conference later this year.
Study 903 is the first three-year, international, randomized, double-blind, clinical trial of an HIV drug regimen in antiretroviral-naive patients. In this study, 600 patients were randomized to receive either a treatment regimen of Viread, lamivudine and efavirenz (n=299) or stavudine, lamivudine and efavirenz (n=301) over 144 weeks.
"There is a great need for long-term clinical data evaluating the efficacy, durability and tolerability of antiretroviral regimens," said Joel Gallant, MD of Johns Hopkins University School of Medicine, and the study's principal investigator. "These results are important for both physicians and patients, who are increasingly interested in identifying well tolerated, convenient regimens that can be effective at suppressing HIV replication over an extended period of time without significant long-term toxicity."
At 144 weeks, data show that Viread and stavudine had comparable success in controlling viral replication, with 73 and 69 percent of patients, respectively, showing a reduction of viral load to less than 50 copies/mL. The study discontinuation rate was comparable in each arm of the study, with 18 and 21 percent of patients in the Viread and stavudine arms, respectively, discontinuing from the study. The most common adverse events observed were viral infection, diarrhea and headache, and each occurred with similar frequency in the two study arms.
Patients receiving Viread were less likely to develop investigator-defined lipodystrophy, characterized as changes in body shape, compared to those on stavudine, with three percent of Viread patients developing this condition compared to 19 percent of stavudine patients. In a sub-study designed to measure changes in limb fat, Viread patients had a mean total limb fat of 8.7 kg compared to 4.4 kg measured for those receiving stavudine. Loss of limb fat, or peripheral lipoatrophy, is a hallmark of lipodystrophy, which has been associated with long-term administration of some anti-HIV medications and with HIV disease.
Changes in fasting lipid levels (triglycerides and cholesterol) were notably higher in the stavudine treatment group. For patients receiving stavudine, the mean increase from baseline in triglycerides was 134 mg/dL compared to 1 mg/dL for those on Viread. Total cholesterol among stavudine patients increased by 58 mg/dL from baseline, compared to 30 mg/dL for those receiving Viread.
Data from the 144-week analyses suggest that resistance to Viread is slow to develop and occurs infrequently among treatment-naive patients. In vitro data and earlier clinical trials show that Viread selects for K65R, a reverse transcriptase mutation. Through 96 weeks of the study, the K65R mutation developed in a total of eight patients (2.7 percent) in the Viread arm versus two patients (0.7 percent) in the stavudine arm. No additional cases of the K65R mutation were observed among patients in either arm of the study at 144 weeks.
In this study, Viread and stavudine had comparable renal safety profiles with no patient in the Viread arm discontinuing the study for a renal-related abnormality and less than one percent of patients in each arm experiencing serum creatinine levels of more than 2 mg/dL. Mean decreases in lumbar spine and hip bone mineral density after three years of treatment were less than three percent in both arms of the study. Bone mineral density reduction observed in Study 903 was non-progressive, with no substantial changes from the 24- and 48-week intervals to week 144. At 144 weeks, a total of five fractures were observed in the Viread arm compared to eleven fractures in stavudine-treated patients.
"One of the most pressing needs in HIV therapy today is for effective regimens that patients can tolerate over extended periods, thereby increasing the chance for success of that regimen," said John Martin, PhD, President and Chief Executive Officer of Gilead Sciences. "At Gilead, our goal is to partner with the medical community to best understand the role our anti-HIV drugs can play in patients' regimens. We are pleased to see the high numbers of patients who completed three years of this important study, and we will continue evaluating data in a sub-group of patients through five years."
Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Viread is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI) approved for the treatment of HIV in the United States and Europe. The drug works by blocking reverse transcriptase, an enzyme involved in the replication of HIV. Viread is dosed as one tablet once daily taken orally with or without food.
Assessment of adverse reactions is based on one study of treatment-experienced patients and one study of treatment-naive patients. In Study 907, a total of 550 treatment-experienced patients received treatment with Viread 300 mg (n=368) or placebo (n=182) for 24 weeks followed by extended treatment with the drug. In Study 903, a total of 600 patients received treatment with Viread (n=299) or stavudine (n=301) in combination with lamivudine and efavirenz for 48 weeks. The most common adverse events in these patients were dizziness and mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting and flatulence.
In clinical practice, a number of adverse events, including renal impairment, nausea, rash and asthenia (weakness) have been reported. Renal impairment occurred most often in patients with underlying systemic or renal disease or in patients taking concomitant nephrotoxic agents, though some cases have appeared in patients without identified risk factors. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination with other antiretrovirals. In patients co-infected with HIV and the hepatitis B virus, exacerbations of hepatitis B have been reported in patients after discontinuation of Viread. Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The clinical significance of changes in BMD and biochemical markers is unknown and follow-up is continuing to assess long-term impact.
Sciences Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes therapeutics to advance the care of patients suffering from life-threatening diseases worldwide. The company has six marketed products and focuses its research and clinical programs on anti-infectives. Headquartered in Foster City, CA, Gilead has operations in the United States, Europe and Australia.
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors including the risk that in a clinical setting or through longer treatment periods Gilead may not continue to observe the data observed in this study. These risks and uncertainties could cause actual results to differ materially from those referred to in the forward-looking statements. Risks are described in detail in the Gilead Annual Report on Form 10-K for the year ended December 31, 2002 and in Gilead's Quarterly Reports on Form 10-Q, all of which are on file with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead and Gilead assumes no obligation to update any such forward-looking statements.
Viread is a registered trademark of Gilead Sciences, Inc.
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