July 14, 2003
Phase III Trial of Emtriva, New Once-Daily Capsule for HIV, Shows Continued Response Through 60 Weeks
PARIS--(BUSINESS WIRE)--July 14, 2003-- Data from Study 301 and Additional Emtriva Abstracts Presented at 2nd International Conference on HIV Pathogenesis and Treatment
Gilead Sciences, Inc. (Nasdaq: GILD) today announced the results of a Phase III clinical trial that show Emtriva(TM) (emtricitabine), the company's new once-daily nucleoside reverse transcriptase inhibitor (NRTI) for HIV, is significantly more potent in suppressing replication of the virus when compared with another NRTI, stavudine (d4T), in combination with other antiretroviral agents. The data were presented this week at the 2nd International AIDS Society Conference on HIV Pathogenesis and Treatment in Paris.
Emtriva, which is dosed as one capsule taken once daily, was approved by the U.S. Food and Drug Administration on July 2 for the treatment of HIV. Dr. Francois Raffi of the Centre Hospitalier Universitaire de Nantes, France described the 60-week results of Phase III Study 301 in an oral presentation today (Abstract #38). Several additional abstracts on Emtriva and Viread(R) (tenofovir disoproxil fumarate), Gilead's nucleotide analogue for HIV, will be presented at the conference.
"This study suggests that over time Emtriva continues to outperform stavudine, a thymidine-analogue NRTI, in terms of both its efficacy and tolerability," said Dr. Raffi. "Regimens that can be given once daily and have favorable side effect profiles are important for physicians and their patients, who increasingly are concerned about adherence and quality-of-life issues."
Study 301 enrolled 571 treatment-naive patients who at baseline had HIV RNA (viral load) of at least 5000 copies/mL. Patients were randomized (1:1) to receive once-daily Emtriva, or twice-daily stavudine, in combination with didanosine (ddl), another NRTI, and efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI). The median viral load at baseline was 4.9 log and the median CD4 cell count was 288 cells/mm3. Based on an interim analysis, the Data Safety Monitoring Board (DSMB) recommended that the trial be unblinded and all patients offered the regimen containing Emtriva, due to its superiority on primary and secondary endpoints for efficacy and safety. Results at week 60 presented in Paris characterize data from patients who were on blinded treatment assignment, with a median time on study of 60 weeks.
Seventy-nine percent of patients receiving the Emtriva-containing regimen (n=286) had persistent suppression of HIV RNA less than 400 copies/mL at week 60, compared to 63 percent receiving the stavudine-containing regimen (n=285; p less than 0.0001), based on Kaplan Meier estimates. The mean increase in CD4 cell counts was 165 and 137 cells/mm3 for the Emtriva and stavudine groups, respectively (difference not statistically significant).
In addition, Emtriva demonstrated superior tolerability to stavudine in terms of the lower incidence of treatment-emergent side effects. Tolerability failure, defined as the permanent discontinuation of study medication due to clinical adverse events, was 7.4 percent for the Emtriva arm, compared with 16.6 percent for the stavudine arm (p=0.003) based on Kaplan Meier estimates. Adverse events that were significantly less likely to occur among those taking Emtriva included nausea, diarrhea, abnormal dreams, paresthesia, neuropathy, symptomatic hyperlactatemia or lactic acidosis.
"This study demonstrates that Emtriva has an excellent clinical profile on three important fronts -- efficacy, durability and tolerability for patients," said John C. Martin, PhD, President and Chief Executive Officer, Gilead Sciences. "Gilead is dedicated to advancing new therapeutics for the treatment of infectious diseases, and we are pleased to able to share important data from our portfolio of HIV therapeutics at this week's meeting in Paris."
Additional Emtriva Data
Several additional studies of Emtriva will be presented at the conference, including data comparing the effectiveness of once-daily Emtriva with twice-daily abacavir, when used in combination with other antiretrovirals as part of first line therapy (Abstract #547). Thirty-seven treatment-naive patients were randomized (1:1) to receive once-daily Emtriva or twice-daily abacavir in addition to stavudine and efavirenz. At 24 weeks, Emtriva showed comparable efficacy to abacavir, with 83 percent of patients taking Emtriva (n=18) experiencing a reduction in HIV RNA to under 50 copies/mL, compared with 63 percent of patients receiving abacavir (n=19). The CD4 cell count increased in both treatment arms, with a median increase from baseline of 8 percent for patients on the Emtriva-containing regimen and 6 percent for those taking abacavir. In addition, Emtriva demonstrated comparable tolerability to abacavir, with two patients from each study arm discontinuing treatment due to an adverse clinical event.
Emtriva is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults. In controlled clinical studies, Emtriva has been shown to effectively suppress HIV replication when taken in combination with other antiretroviral medications.
In a Phase III clinical trial of 571 patients who had not taken HIV drugs before, 81 percent of patients receiving Emtriva in combination with other antiretroviral drugs (n=286) experienced a reduction in HIV RNA below 400 copies/mL and 78 percent experienced a reduction below 50 copies/mL, versus 68 percent and 59 percent of patients, respectively, in the comparative arm of the study (n=285). In another Phase III study of 440 treatment-experienced patients, Emtriva achieved comparable HIV suppression in patients previously treated with lamivudine. In this study, 77 percent of patients treated with Emtriva in combination with other antiretroviral drugs (n=294) achieved a reduction in viral load below 400 copies/mL and 67 percent achieved below 50 copies/mL, versus 82 percent and 72 percent, respectively, in the control arm (n=146).
An application for marketing approval of Emtriva for the treatment of HIV was submitted to the European regulatory authorities in December 2002. Gilead anticipates that the European evaluation will be completed in 2004. The company has retained worldwide rights to Emtriva and intends to market the product in the United States and, pending approval, in Europe through its own commercial organization.
More than 2000 HIV-infected adults have been treated with Emtriva for periods of 10 days to 200 weeks in Phase I, II and III clinical trials. Assessment of adverse events in the approved package insert is based on pooled data from two Phase III studies in which 571 treatment-naive and 440 treatment-experienced patients received Emtriva (n=580) or a comparator drug (n=431) for 48 weeks.
The most common adverse events that occurred in patients receiving Emtriva were headache, diarrhea, nausea and rash, which were generally of mild to moderate severity. Approximately one percent of patients discontinued participation in the clinical studies due to 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 (excess pigmentation) on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance are unknown. 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 chronic hepatitis B, exacerbations of hepatitis B have been reported in patients after discontinuation of Emtriva. Patients with renal impairment should be carefully monitored and may require dose interval adjustments.
Co-formulation with Viread
Gilead is currently conducting research to determine the pharmacokinetics and stability of a co-formulation of Emtriva and Viread. A once-daily pill containing both antiretrovirals could potentially reach the market by early 2005. As part of Gilead's ongoing clinical research, the company is designing a study to examine the efficacy of a regimen containing Emtriva, Viread and efavirenz compared with a regimen of Combivir(R) (zidovudine and lamivudine) and efavirenz. Gilead expects to initiate this study before year end.
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 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 risks and uncertainties related to the pharmacokinetics, stability and ultimately the company's ability to obtain regulatory approval of a co-formulation of Emtriva and Viread, the risk that the safety and efficacy data obtained in controlled clinical trials for Emtriva will not be observed in an uncontrolled clinical setting, the risk that Gilead's comparative study may not provide positive data for Emtriva and the risk that the European Medicines Evaluation Agency (EMEA) may not see the advantages of Emtriva over lamivudine and may therefore be reluctant to grant regulatory approval for Emtriva. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. These and other 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.
Emtriva is a trademark and Viread is a registered trademark of Gilead Sciences, Inc.
For full U.S. prescribing information on Emtriva, please call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com or www.emtriva.com.
CONTACT: Gilead Sciences, Inc. Susan Hubbard, 650/522-5715 (Investors) Amy Flood, 650/522-5643 (Media) James Loduca, +44 77 40 600 616 (Media) (Paris) SOURCE: Gilead Sciences, Inc.