October 28, 2003
Gilead Sciences' HIV Drug Emtriva Approved for Marketing in European Union
Emtriva is the newest nucleoside reverse transcriptase inhibitor (NRTI) for the treatment of HIV infection, and is dosed as a single capsule taken once a day as part of combination therapy. The drug works by inhibiting reverse transcriptase, an enzyme crucial for HIV replication. By interfering with this process, the drug can help to 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. Emtriva will be available in individual European countries as local reimbursement approvals are obtained.
"Physicians and patients know that adherence is crucial to treatment success, and by reducing the number of pills a patient must take each day and improving a patient's ability to tolerate therapy, adherence may be improved," said Dr. Francois Raffi of the Centre Hospitalier Universitaire de Nantes, France. "With its once-daily dosing, favorable safety and tolerability profile and potent activity against HIV, Emtriva offers a new treatment option in the fight against HIV."
Emtriva is Gilead Sciences' second once-daily antiretroviral for the treatment of HIV. The compound was licensed from Emory University in the United States in 1996. Gilead's first anti-HIV medication, Viread® (tenofovir disoproxil fumarate), a one-tablet, once-daily nucleotide reverse transcriptase inhibitor, was cleared for marketing by the European Commission in February 2002. The company is developing a fixed-dose co-formulation of Emtriva and Viread, which could potentially be available by 2005. Emtriva is Gilead's third antiviral to receive approval in less than two years, following Viread for HIV and Hepsera® (adefovir dipivoxil 10 mg) for chronic hepatitis B, which received European approval in March 2003.
"The approval of our second anti-HIV medication in the European Union reflects Gilead's commitment to improving the lives of people with HIV through the introduction of more tolerable treatments," said John C. Martin, PhD, President and CEO of Gilead Sciences. "Emtriva and Viread offer physicians and patients an effective, once-daily foundation for the management of HIV disease."
The Marketing Authorisation Application (MAA) for Emtriva was submitted for review under the centralized procedure in January 2003 by Triangle Pharmaceuticals, which was acquired by Gilead Sciences later that month. The U.S. Food and Drug Administration (FDA) granted marketing approval for Emtriva 200 mg hard capsules in the United States on July 2, 2003.
HIV in Europe
An increasing number of people are living with HIV in Western Europe. An estimated 570,000 people were living with HIV in 2002, an increase of 10 percent compared to 520,000 in 2000. A recent study found that 10 percent of newly infected patients in Europe from 1999 to 2002 had strains of the virus that were resistant to HIV medications. Resistance is more likely to emerge when patients fail to adhere to their drug regimens.
Emtriva is indicated for the treatment of HIV-infected adults and children in combination with other antiretroviral agents. This indication is based on studies in treatment-naive patients and treatment-experienced patients with stable virological control. There is no experience with the use of Emtriva in patients who are failing their current regimen or who have failed multiple regimens. When deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the patterns of mutations associated with different medicinal products and the treatment history of the individual patient. Where available, resistance testing may be appropriate.
Emtriva is dosed once daily and can be taken with or without food. In controlled clinical studies, Emtriva has been shown to effectively suppress HIV replication when taken in combination with other antiretroviral medications. Emtriva has reduced the level of HIV in the blood for up to 48 weeks among patients starting antiretroviral treatment for the first time, as well as in treatment-experienced individuals with stable virological control.
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. Adverse drug reactions with at least a possible relationship to study drug were evaluated. Assessment of these adverse drug reactions is based on data from three studies in adults (n=1479) and two pediatric studies (n=114). In the adult studies, 1039 treatment-naive and 440 treatment-experienced patients received Emtriva (n=814) or comparator medicinal product (n=665) for 48 weeks in combination with other antiretroviral medicinal products. In the pediatric studies, treatment-naive (n=83) and treatment-experienced (n=31) pediatric patients aged four months to 18 years were treated with Emtriva in combination with other antiretroviral agents.
The most common adverse reactions observed in the studies described above include headache, diarrhea, nausea and elevations in creatine kinase. Additionally, as outlined in the U.S. prescribing information, skin discoloration was observed at a higher frequency in Emtriva versus control groups. Skin discoloration, manifested by hyperpigmentation (excess pigmentation) on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance of this adverse event are unknown.
Special warnings and precautions for use are included in the Summary of Product Characteristics regarding monitoring of patients with renal impairment who may require dose or dose interval adjustment. Special warnings and precautions for use also are included for monitoring of patients co-infected with HIV and HBV after stopping Emtriva treatment for evidence of exacerbations of hepatitis B, as exacerbations have been seen following discontinuation of Emtriva in chronic hepatitis B-infected patients, and monitoring of patients with chronic hepatitis B or C who are at an increased risk of experiencing severe, and potentially fatal, hepatic adverse events when treated with combination antiretroviral therapy. 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. Combination antiretroviral therapy has also been associated with lipodystrophy.
Emtriva is available as a 200 mg capsule for use in adults and also is available as a 10 mg/mL oral solution for use in infants older than four months of age, children and patients who are unable to swallow hard capsules and patients with renal insufficiency who require dose reduction. Please refer to the Summary of Product Characteristics for Emtriva 10 mg/mL oral solution.
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 stability, pharmacokinetics 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, and the risk that physicians may not see advantages of Emtriva over lamivudine and may therefore be reluctant to prescribe Emtriva. 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 and Hepsera are registered trademarks of Gilead Sciences, Inc.
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Department at 1-800-GILEAD-5 (1-800-445-3235), or visit
Gilead Sciences, Inc. Susan Hubbard, 650-522-5715 (Investors) Amy Flood, 650-522-5643 (Media)