February 28, 2005
48-Week Data Comparing Viread Versus Abacavir as Replacement for Thymidine Analogue in Lipoatraphic HIV Patients Presented at the 12th Conference on Retroviruses and Opportunistic Infections
BOSTON--(BUSINESS WIRE)--Feb. 28, 2005--Gilead Sciences (Nasdaq:GILD) today announced the presentation of preliminary 48-week data from the RAVE (Randomized Abacavir Viread Evaluation) study at the 12th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. The RAVE Study, conducted by Chelsea and Westminster Hospital in London, is a randomized, open-label, 48-week comparative trial of abacavir or Viread(R) (tenofovir disoproxil fumarate) as replacement for a thymidine analog as part of highly active antiretroviral therapy in HIV-infected patients with lipoatrophy and controlled HIV RNA. Results from the study were presented last week by the study's principal investigator, Graeme Moyle, MD, Associate Director of HIV Research, Chelsea and Westminster Hospital as an oral late breaker (Oral 44LB).
"As patients live longer, clinical management of side effects such as lipoatrophy is of increasing concern for doctors and their patients," said Dr. Moyle. "These data provide valuable insight on ways to construct combination HIV regimens that may potentially address those challenges."
The RAVE study is designed to evaluate changes in limb fat in HIV patients with moderate to severe lipoatrophy and controlled HIV RNA (viral load less than 50 copies/mL) following a switch from a thymidine analog to a non-thymidine analog antiretroviral taken as part of combination therapy. Lipoatrophy is defined as a loss of fat in the limbs and facial area.
The study enrolled 105 adult patients receiving the thymidine analogs stavudine, or d4T (n=71) or zidovudine, or AZT (n=34) as part of their combination therapy. Patients were randomized to replace the thymidine analog with either twice-daily abacavir (n=53) or once-daily Viread (n=52) while maintaining stable background therapy. At study enrollment, all patients had not previously received therapy with abacavir or Viread. At baseline, limb fat was similar between the two groups (median of 2.9 kg in the abacavir group vs. 3.0 kg in the Viread group), as measured by dual-energy x-ray absorptiometry (DEXA). The primary endpoint of the study was change in limb fat at week 48, using an intent-to-treat analysis. Secondary endpoints included HIV RNA, adverse events, visceral fat mass (by CT scan) and fasting metabolic parameters.
Results presented at the conference suggest that at 48 weeks there was a significant increase in limb fat in both groups from baseline values, but not a significant difference between study arms (median of 0.3 kg in the abacavir group vs. 0.4 kg in the Viread group). Median changes in visceral and subcutaneous abdominal fat by CT scan were also similar in the abacavir vs. Viread group (-1 vs. 7 and 11 vs. 8 cm3, respectively).
Discontinuations of study drug due to adverse events were more common in the abacavir (n=3, hypersensitivity reactions) vs. Viread (n=1, diarrhea) arm. Median changes from baseline in total cholesterol, LDL and triglycerides in the abacavir vs. Viread arms were 0 vs. -0.2, 0 vs. -0.1, and 0 vs. -0.17 mmol/l, respectively. The difference between the two arms for each of these parameters was statistically significant (p=0.016, 0.043 and 0.031, respectively).
No significant difference between the abacavir and Viread groups was observed in median change in bone mineral density T-scores by DEXA (0 vs. -0.1). Virological suppression was also similarly maintained in the abacavir vs. Viread group (91 vs. 100 percent of patients had HIV RNA below 50 copies/mL at week 48).
Data from the RAVE study have not been reviewed by FDA. Changes in body fat have been observed in patients taking Viread and other anti-HIV medicines. The cause and long term health effect of these conditions are unknown. For the detailed indication and important safety information from the U.S. prescribing information for Viread, see below.
It is important that patients be aware that HIV medications must be taken as part of combination regimens and that they do not cure HIV infection, nor do they reduce its transmission.
Important Safety Information from U.S. Prescribing Information for Viread
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. Viread is not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of the drug has not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Viread. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue Viread and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of Viread in treatment-naive adults and in treatment-experienced adults. There are no study results demonstrating the effect of Viread on clinical progression of HIV-1. The use of Viread should be considered for treating adult patients with HIV-1 strains that are expected to be susceptible to tenofovir as assessed by laboratory testing or treatment history.
Drug interactions have been observed when didanosine, atazanavir or lopinavir/ritonavir is co-administered with Viread and dose adjustments may be necessary. Data are not available to recommend a dose adjustment of didanosine for patients weighing less than 60 kg. Patients on atazanavir or lopinavir/ritonavir plus Viread should be monitored for Viread-associated adverse events which may require discontinuation. When co-administered with Viread, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.
Renal impairment, including serious cases, has 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. 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. The most common adverse events and those occurring in more than 5 percent of patients receiving Viread with other antiretroviral agents in clinical trials include asthenia, pain, abdominal pain, headache, nausea, diarrhea, vomiting, rash (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash and pustular rash), flatulence, dizziness and depression. Less than 1 percent of patients discontinued participation because of gastrointestinal events.
The parent compound of Viread, tenofovir, was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, 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 the safety and efficacy data obtained through the RAVE study will not be observed through longer treatment periods or in other studies. 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, 2003 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.
For full prescribing information, please visit www.Viread.com.
Viread is a registered trademark of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
CONTACT: Gilead Sciences, Inc.
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SOURCE: Gilead Sciences, Inc.