October 31, 2004
Interim 24-Week Data from Study 934 Comparing a Regimen of Viread and Emtriva Versus Combivir, Both in Combination with Efavirenz, in Patients with HIV Presented at 44th ICAAC
WASHINGTON--(BUSINESS WIRE)--Oct. 31, 2004--Gilead Sciences (Nasdaq:GILD) today announced the presentation of 24-week data from an ongoing clinical trial (Study 934) that suggest treatment-naive patients with HIV who received a once-a-day regimen of Viread(R) (tenofovir disoproxil fumarate 300 mg), Emtriva(R) (emtricitabine 200 mg) and efavirenz (600 mg) had fewer adverse event-related study discontinuations compared to those who received a regimen of twice-daily Combivir(R) (lamivudine 150 mg/zidovudine 300 mg) and once-daily efavirenz (600 mg).
Study 934 is an ongoing, open-label, Phase III clinical trial comparing a once-a-day regimen of Viread and Emtriva versus twice-daily Combivir, both in combination with once-daily efavirenz in more than 500 patients in the United States and Europe. The study, which has a 48-week primary endpoint, was recently extended to 96 weeks in duration. The primary endpoint is the proportion of patients achieving and maintaining viral load reductions to less than 400 copies/mL at week 48, using the Time to Loss of Virologic Response (TLOVR) algorithm, as specified in FDA guidance. Twenty-four week data from a planned interim analysis were presented today by Brian Gazzard, MD, Chelsea and Westminster Hospital and Clinical Research Director, Imperial College, London at the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) as an oral late breaker (Presentation #H-1137c).
"The convenience and tolerability of an antiretroviral regimen is increasingly important as patients remain on therapy for longer periods of time," said Dr. Gazzard. "Although both triple-drug regimens are relatively convenient, we observed a difference in the two arms, with more patients discontinuing in the Combivir group due to adverse events."
The U.S. FDA recently granted accelerated marketing approval of Truvada(TM) (emtricitabine and tenofovir disoproxil fumarate), a fixed-dose tablet containing Viread and Emtriva, to be taken once a day in combination with other antiretrovirals.
At study entry, no patients had previously received antiretroviral therapy and all had a viral load greater than 10,000 copies/mL. The median viral load at baseline was 100,000 copies/mL. There were no CD4 cell count restrictions for study participants. The median CD4 cell count at baseline was 237 cells/mm(3) and 13 percent of patients entered the study with CD4 cell counts below 50. The 24-week interim data presented at ICAAC are based on analyses of the intent to treat (ITT) study population of 509 patients. This includes the pre-specified population of 487 patients described in the company's preliminary 24-week data announcement, and an additional 22 patients with pre-existing non nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations.
Using the TLOVR algorithm, at 24 weeks, 87 percent of patients in the Viread/Emtriva arm (n=255) achieved and maintained a reduction of viral load to less than 400 copies/mL compared to 78 percent of patients in the Combivir arm (n=254) (p=0.010; 95% CI, +1.9% to +14.9%). Similarly, 73 percent of patients in the Viread/Emtriva arm versus 65 percent in the Combivir arm achieved and maintained a reduction of viral load to less than 50 copies/mL, (p=0.038; 95% CI, +0.5% to +16.2%). The mean increase in CD4 cell count for patients in the Viread/Emtriva arm was 129 cells/mm(3) compared to 111 cells/mm(3) in the Combivir arm.
The study regimen discontinuation rate due to adverse events was higher in the Combivir arm, with 9 percent of patients discontinuing from the study versus 3 percent in the Viread/Emtriva arm (p=0.008). The most common adverse events leading to study discontinuation were anemia, nausea, fatigue and vomiting. Mutations associated with efavirenz resistance and lamivudine and Emtriva resistance developed similarly in both arms, with no patients developing Viread-related (K65R) or thymidine analogue mutations. The renal safety profile was similar in both arms.
Important Safety Information
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, Emtriva and Truvada are not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of these drugs 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 or Emtriva. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue Viread, Emtriva or Truvada and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Changes in body fat have been observed in patients taking Viread, Emtriva, Truvada and other anti-HIV medicines. The cause and long term health effect of these conditions are unknown.
It is important that patients be aware that HIV medications must be taken as part of combination regimens and do not cure HIV infection, nor do they reduce its transmission.
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.
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. 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.
Emtriva is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts from controlled studies of 48 weeks duration in antiretroviral-naive patients and antiretroviral-treatment-experienced patients who were virologically suppressed on an HIV treatment regimen. In antiretroviral-treatment-experienced patients, the use of Emtriva may be considered for adults with HIV strains that are expected to be susceptible to Emtriva as assessed by genotypic or phenotypic testing.
Adverse events that occurred in more than 5 percent of patients receiving Emtriva with other antiretroviral agents in clinical trials include abdominal pain, asthenia (weakness), headache, diarrhea, nausea, vomiting, dizziness and rash. Approximately 1 percent of patients discontinued participation because of these events. All adverse events were reported with similar frequency in Emtriva and control treatment groups with the exception of skin discoloration which was reported with higher frequency in the Emtriva treated group. Skin discoloration, manifested by hyperpigmentation on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance are unknown.
Truvada is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults. Safety and efficacy studies using Truvada tablets or using Emtriva and Viread in combination are ongoing.
Both components of Truvada have been studied individually, as part of multi-drug regimens and have been found to be safe and effective. Since Emtriva and lamivudine (3TC) are comparable in their structure, resistance profiles, and efficacy and safety as part of multi-drug regimens, existing data from the use of lamivudine and Viread in combination have been extrapolated to support use of Truvada tablets for the treatment of HIV-1 infection in adults. Therefore, in treatment-naive patients, Truvada should be considered as an alternative to the combination of Viread and lamivudine for those patients who might benefit from a once-daily regimen. In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
There are no study results demonstrating the effect of Truvada on clinical progression of HIV-1, and it is not recommended that Truvada be used as a component of a triple nucleoside regimen.
Truvada should not be used with Emtriva or Viread, or other drugs containing lamivudine, including Combivir(R), Epivir(R), Epivir-HBV(R), Epzicom(TM) or Trizivir(R).
Two-hundred eighty-three patients have received combination therapy with Emtriva and Viread with either a non-nucleoside reverse transcriptase inhibitor or protease inhibitor for 24 to 48 weeks in ongoing clinical studies. Based on these limited data, no new patterns of adverse events were identified and there was no increased frequency of established toxicities. For additional safety information about Emtriva or Viread in combination with other antiretroviral agents, please see "About Emtriva" and "About Viread," above.
About Gilead 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 seven marketed products, and focuses its research and clinical programs on anti-infectives. Headquartered in Foster City, CA, Gilead has operations in North America, Europe and Australia.
This press release includes analyses of data that have not been reviewed by the FDA. This release also 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 24 weeks of Study 934 will not be observed through 48 weeks 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.Truvada.com, www.Viread.com or www.Emtriva.com.
Truvada is a trademark and Emtriva and Viread are registered trademarks 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 800-GILEAD-5 or 650-574-3000.
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SOURCE: Gilead Sciences, Inc.