Phase III Trial of Emtriva, New Once-Daily Capsule for HIV, Shows Continued Response Through 60 Weeks.Business Editors/Health/Medical Writers PARIS--(BUSINESS WIRE)--July 14, 2003 Data from Study 301 and Additional Emtriva Abstracts Presented at 2nd International Conference on HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. Pathogenesis and Treatment Gilead Sciences, Inc. (Nasdaq: GILD) today announced the results of a Phase III clinical trial Noun 1. phase III clinical trial - a large clinical trial of a treatment or drug that in phase I and phase II has been shown to be efficacious with tolerable side effects; after successful conclusion of these clinical trials it will receive formal approval from the that show Emtriva(TM) (emtricitabine), the company's new once-daily nucleoside reverse transcriptase inhibitor Noun 1. nucleoside reverse transcriptase inhibitor - an antiviral drug used against HIV; is incorporated into the DNA of the virus and stops the building process; results in incomplete DNA that cannot create a new virus; often used in combination with other drugs (NRTI Noun 1. NRTI - an antiviral drug used against HIV; is incorporated into the DNA of the virus and stops the building process; results in incomplete DNA that cannot create a new virus; often used in combination with other drugs ) 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 The International AIDS Society (IAS) is an international society for scientists, health care and public health workers, and others engaged in HIV/AIDS prevention, control and care. 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 tenofovir disoproxil fumarate Viread Pharmacologic class: Nucleoside analog reverse transcriptase inhibitor Therapeutic class: Antiretroviral Pregnancy risk category B ), 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 Results Study 301 enrolled 571 treatment-naive patients who at baseline had HIV RNA HIV RNA AIDS RNA of HIV origin, a serum marker of a Pt's 'HIV-ness,' now the standard by which Pt response to antiretovirals is evaluated; HIV RNA levels correlate with CD4+ count, response to antiviral therapy, clinical stage and disease progression. (viral load viral load n. The concentration of a virus, such as HIV, in the blood. viral load, n a measure of the number of virus particles present in the bloodstream, expressed as copies per milliliter. ) of at least 5000 copies/mL. Patients were randomized ran·dom·ize tr.v. ran·dom·ized, ran·dom·iz·ing, ran·dom·iz·es To make random in arrangement, especially in order to control the variables in an experiment. (1:1) to receive once-daily Emtriva, or twice-daily stavudine, in combination with didanosine didanosine /di·dan·o·sine/ (-dan´o-sen) 2, an analogue of dideoxyadenosine; an antiretroviral agent used for the treatment of advanced HIV-1 infection and acquired immunodeficiency syndrome, administered orally. (ddl), another NRTI, and efavirenz efavirenz /ef·a·vi·renz/ (ef´ah-vi?renz) an antiretroviral, inhibiting reverse transcriptase; used in the treatment of HIV infection. e·fa·vir·enz n. , a non-nucleoside reverse transcriptase inhibitor Noun 1. non-nucleoside reverse transcriptase inhibitor - an antiviral drug used against HIV; binds directly to reverse transcriptase and prevents RNA conversion to DNA; often used in combination with other drugs NNRTI (NNRTI NNRTI Non-nucleoside reverse transcriptase inhibitor, see there ). 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 DSMB Data & Safety Monitoring Board Clinical research A committee of independent clinical research experts who review data in ongoing clinical trials, ensuring that participants are not exposed to undue risk, and look for any differences in effectiveness ) 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 paresthesia /par·es·the·sia/ (par?es-the´zhah) morbid or perverted sensation; an abnormal sensation, as burning, prickling, formication, etc. par·es·the·sia or par·aes·the·sia n. , 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. About Emtriva 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. Safety Profile 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 comparator Instrument for comparing something with a similar thing or with a standard measure, in particular to measure small displacements in mechanical devices. In astronomy, the blink comparator is used to examine photographic plates for signs of moving bodies. 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 dis·col·or·a·tion n. 1. a. The act of discoloring. b. The condition of being discolored. 2. A discolored spot, smudge, or area; a stain. Noun 1. , which was reported with higher frequency in the Emtriva treated group. Skin discoloration, manifested by hyperpigmentation Hyperpigmentation Definition Hyperpigmentation is the increase in the natural color of the skin. Description Melanin, a brown pigment manufactured by certain cells in the skin called melanocytes, is responsible for skin color. (excess pigmentation pigmentation, name for the coloring matter found in certain plant and animal cells and for the color produced thereby. Pigmentation occurs in nearly all living organisms. ) on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance are unknown. Lactic acidosis and severe hepatomegaly hepatomegaly /hep·a·to·meg·a·ly/ (hep?ah-to-meg´ah-le) enlargement of the liver. hep·a·to·meg·a·ly n. The abnormal enlargement of the liver. Also called megalohepatia. with steatosis steatosis /ste·a·to·sis/ (ste?ah-to´sis) fatty change. ste·a·to·sis n. See fatty degeneration. steatosis fatty degeneration. See also muscular 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 zidovudine /zi·do·vu·dine/ (zi-do´vu-den) a synthetic nucleoside (thymidine) analogue that inhibits replication of some retroviruses, including the human immunodeficiency virus; used in the treatment of HIV infection and AIDS. 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 The Private Securities Litigation Reform Act of 1995 (PSLRA) implemented several significant substantive changes affecting certain cases brought under the federal securities laws, including changes related to pleading, discovery, liability, class representation and awards fees and 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 (Europe, Middle East, Africa) Refers to that region of the world. For example, one might see products packaged differently for the UK, EMEA and Asia Pacific markets. ) 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. |
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