August 26, 2004
Gilead Announces Preliminary 24-Week Data from Study 934 Comparing Viread and Emtriva to Combivir Both in Combination With Efavirenz In Patients With HIV
Fixed-Dose Combination of Viread and Emtriva Recently Approved as Truvada(TM)
FOSTER CITY, Calif.--(BUSINESS WIRE)--Aug. 26, 2004-- Gilead Sciences (Nasdaq:GILD) today announced preliminary data from a planned interim 24-week analysis of the company's ongoing Study 934. This study, a 48-week clinical trial, was designed to compare a regimen of Viread(R) (tenofovir disoproxil fumarate), Emtriva(R) (emtricitabine) and efavirenz to Combivir(R) (lamivudine 150 mg/zidovudine 300 mg) and efavirenz in more than 500 treatment-naive patients with HIV. Preliminary results show a statistically significant difference favoring Viread/Emtriva in the percentage of patients who achieved and maintained HIV RNA less than 400 copies/mL at 24 weeks, based on the FDA Time to Loss of Virologic Response algorithm (TLOVR).
Study 934 is a Phase III, multicenter, open-label 48-week clinical trial that enrolled 517 HIV-infected patients in the United States and Europe. The prespecified intent-to-treat population includes 487 patients. Participants in one arm of the study receive Viread 300 mg, Emtriva 200 mg and efavirenz 600 mg, all dosed once daily. Patients in the comparator arm receive Combivir twice daily and efavirenz 600 mg once daily. At study entry, patients had not previously received antiretroviral therapy and had HIV RNA greater than 10,000 copies/mL. The study is ongoing.
Based on a planned interim 24-week analysis (n=487), preliminary data show 88 percent of patients in the Viread/Emtriva arm compared to 80 percent of patients in the Combivir arm achieved and maintained HIV RNA less than 400 copies/mL at week 24 using the TLOVR algorithm (p=0.019; 95% CI, +0.8% to +13.3%). In the TLOVR algorithm, 3 percent of patients on the Viread/Emtriva arm compared to 9 percent of patients on the Combivir arm discontinued from study regimen due to adverse events (p=0.013). Patients had an increase from baseline of 129 and 111 CD4 cells/mm(3) in the Viread/Emtriva and Combivir arms, respectively. The incidence of grade 3 or 4 clinical adverse events was 9 percent for the Viread/Emtriva arm compared to 15 percent for the Combivir arm. Gilead expects to present these data at a scientific conference later this year.
On August 2, the FDA granted marketing approval of Truvada(TM) (emtricitabine and tenofovir disoproxil fumarate), a fixed-dose combination of the company's anti-HIV medications Emtriva and Viread. Truvada combines 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate in one tablet, taken once a day in combination with other antiretroviral agents.
Viread, Emtriva and Truvada work by blocking reverse transcriptase, an enzyme crucial for viral replication. By interfering with the replication process, these drugs, when combined with other anti-HIV medications, can help lower the amount of HIV or "viral load" in a patient's body and increase the number of immune system cells (called T cells or CD4 cells). Both of these changes are generally associated with improving a patient's health and decreasing the likelihood of AIDS-related illnesses. The use of Viread, Emtriva and Truvada may be considered for treating patients with HIV strains that are expected to be susceptible as assessed by laboratory testing or treatment history.
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.
Adverse events that occurred in more than 5 percent of patients receiving Viread with other antiretroviral agents in clinical trials include headache, nausea, diarrhea, vomiting, rash 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.
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 and other anti-HIV medicines. The cause and long term health effect of these conditions are unknown.
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 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 1-800-GILEAD-5 or 1-650-574-3000.
CONTACT: Gilead Sciences
Tricia Petersen, 650-522-5839 (Investors)
Amy Flood, 650-522-5643 (Media)
SOURCE: Gilead Sciences