November 17, 2005
Preliminary 24-Week Data Evaluating the Impact of Switching from Twice-Daily Combivir(R) to Once-Daily Truvada(R) in Patients with HIV Presented at 10th European AIDS Conference
DUBLIN, Ireland--(BUSINESS WIRE)--Nov. 17, 2005--Gilead Sciences, Inc. (Nasdaq:GILD) today announced the presentation of preliminary 24-week data from the COMET (Combination of Efavirenz and Truvada) study at the 10th European AIDS Conference (EACS), November 17-20, 2005 in Dublin, Ireland. Data suggest that in HIV-infected treatment-experienced patients who switched from twice-daily Combivir(R) (lamivudine 150 mg/zidovudine 300 mg) to once-daily Truvada(R) (emtricitabine and tenofovir disoproxil fumarate), both in combination with efavirenz, the percentage of patients that achieved virologic suppression below 50 copies/mL was significantly higher at week 24 compared to baseline. Hemoglobin levels also increased significantly from baseline. Data will be presented (Poster #PE7.3/5) by study investigator Peter Ruane, MD of Lifesource Medical Inc. in Los Angeles, California.
"The simplicity, tolerability and virologic benefit provided by a fixed-dose combination backbone are important considerations in helping promote long-term positive clinical outcomes," said Norbert Bischofberger, PhD, Executive Vice President, Research and Development, Gilead Sciences. "These data suggest that switching virologically suppressed patients from Combivir to Truvada may be a valuable treatment strategy for physicians and patients who are seeking to further simplify a regimen or address side effects observed with other therapies."
The COMET study is a U.S.-based, single-arm, multi-center 24-week Phase IV clinical trial evaluating the impact of switching virologically suppressed HIV-infected treatment-experienced patients from a regimen of twice-daily Combivir and once-daily efavirenz to a simplified once-daily regimen of Truvada and efavirenz. Enrollment in the COMET study was completed in August 2005 with 411 patients enrolled in the study. At study entry, all patients were to have received Combivir for at least eight weeks and have a viral load less than 400 copies/mL. Study endpoints include viral suppression less than 400 and 50 copies/mL, change in CD4 cell count, changes in patients' hemoglobin levels and lipid profile and responses to a questionnaire evaluating symptoms, adherence and treatment satisfaction (SATS).
Of the 411 total enrolled patients, 198 reached week 24 at the time of this analysis. Nineteen patients discontinued the study prior to week 24, of which six withdrew due to adverse events, two for pregnancy, five for protocol violation or noncompliance and six were lost to follow up, withdrew consent or withdrew for other reasons. Baseline characteristics were assessed on 217 patients, who either reached week 24 (n=198) or withdrew early from the study (n=19). Of these 217 patients, 86 percent were male, 71 percent were white, 22 percent were black and the median age was 42 years. Eighty-nine percent of patients had taken Combivir for longer than one year and the median duration of prior Combivir use (or use of its component drugs) was four years. Eighty-six percent of patients switched to Truvada for regimen simplification, 6 percent of patients switched because of Combivir-related adverse events and 8 percent of patients cited both regimen simplification and Combivir-related adverse events as reasons for switching.
Based on analysis of all available 24 week data, 76 percent of patients had viral load of less than 50 copies/mL compared to 59 percent at baseline (n=189; p less than 0.001). Ninety-four percent of patients maintained viral load of less than 400 copies/mL (n=189). Hemoglobin increased significantly from baseline (median +0.6 g/dL; n=191; p less than 0.001) with 32 percent of patients experiencing at least 1 g/dL increase in hemoglobin. The most common adverse events observed were nausea, diarrhea and headache. Of the 172 patients who completed a SATS questionnaire, a significantly greater percentage of patients reported being very satisfied with the treatment regimen at 24 weeks (85 percent) compared to baseline (58 percent; p less than 0.001).
Data from the COMET study have not been reviewed by the United States Food and Drug Administration (FDA). Changes in body fat have been observed in patients taking anti-HIV medicines, including the component drugs of Truvada. The cause and long-term health effect of this condition is unknown. For the detailed indication and important safety information from the U.S. prescribing information for Truvada, see below.
The parent compound of one of the component drugs in Truvada, tenofovir disoproxil fumarate, 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. The inventors have agreed to waive their right to a royalty on sales of products containing tenofovir in the developing countries served by the Gilead Access Program to ensure the product can be offered at a no-profit price in parts of the world where the AIDS epidemic has hit the hardest.
It is important that patients be aware that individual HIV medications must be taken as part of combination regimens, and that they do not cure HIV infection or prevent passing HIV to others.
Truvada combines Emtriva(R) (emtricitabine) and Viread(R) (tenofovir disoproxil fumarate) in one tablet taken once a day in combination with other antiretroviral agents. In the United States, 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.
Emtriva and Viread have each been studied as part of multi-drug regimens and have been found to be safe and effective. In clinical study 303, Emtriva and lamivudine (3TC) demonstrated comparable efficacy, safety and resistance patterns as part of multidrug regimens. These data, and those from study 903, in which lamivudine and tenofovir were used in combination, support the use of Truvada for the treatment of HIV-1 infection in treatment-naive adults. In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
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. Truvada is not indicated for the treatment of chronic hepatitis B virus (HBV) infection and its safety and efficacy 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 Truvada and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
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, Epivir(R), Epivir-HBV(R), Epzicom(TM) or Trizivir(R). No drug interaction studies have been conducted using Truvada. Drug interactions have been observed when didanosine, atazanavir, or lopinavir/ritonavir are co-administered with Viread, a component of Truvada, 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 Truvada should be monitored for Truvada-associated adverse events that 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. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Emtriva and Viread.
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.
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 (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash, pustular rash and allergic reaction). 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.
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 and increases in biochemical markers of bone metabolism 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.
For complete prescribing information for Truvada, visit www.truvada.com. For safety and efficacy studies using Emtriva or Viread in combination with other antiretroviral agents, please consult the prescribing information for these products.
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 COMET 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, 2004 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.
Truvada 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.