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FDA Approves New HIV Drug FTC, emtricitabine
  Below are two press releases from today by the FDA and Gilead Sciences.
FDA Press Release
The Food and Drug Administration (FDA) announced on Wednesday, July 2, 2003, the approval of Emtriva (FTC, emtricitabine), a new nucleoside reverse transcriptase inhibitor (NRTI) to be used in combination with other anti-retroviral agents for the treatment of patients with HIV infection. As with other anti-retroviral agents, Emtriva does not cure and does not prevent transmission of HIV infection or AIDS.
Emtriva is indicated for adults age 18 and older. Safety and effectiveness in pediatric patients have not been established. 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. The recommended dose of Emtriva is one 200 mg capsule daily, with or without food.
FDA based its approval on data from two 48 week clinical trials. The first trial was a double-blind, active-controlled multicenter study comparing Emtriva (200 mg once daily) administered in combination with didanosine and efavirenz versus stavudine, didanosine and efavirenz in 571 antiretroviral naive patients. The proportion of patients who achieved and maintained confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 81% (78%) for the Emtriva, didanosine and efavirenz group vs 61% (59%) for the stavudine, didanosine and efavirenz group, respectively. The mean increase from baseline in CD4 cell count was 168 cells/mm3 for the Emtriva arm compared to 134 cells/mm3 for the control arm.
The second trial was an open-label, active-controlled multicenter study comparing Emtriva to lamivudine, in combination with stavudine or zidovudine and a protease inhibitor or NNRTI in 440 treatment experienced patients who were on lamivudine-containing triple-antiretroviral drug regimen for at least 12 weeks prior to study entry, and had HIV-1 RNA * 400 copies/mL. The proportion of patients who achieved confirmed HIV RNA < 400 copies/mL (< 50 copies/mL) through week 48 was 77% (67%) for the Emtriva group vs 82% (72%) for the lamivudine group. The mean increase from baseline in CD4 cell count was 29 cells/mm3 for the Emtriva arm compared to 61 cells/mm3 for the lamivudine arm. The most common adverse events that occurred in patients receiving Emtriva with other antiretroviral agents in clinical trials were headache, diarrhea, nausea, and rash, which were generally of mild to moderate severity. Approximately 1% of patients discontinued participation in the clinical studies due to these events. With the exception of skin discoloration, which was reported with higher frequency in the Emtriva treated group all other adverse events were reported with similar frequency in Emtriva and control treatment groups.
Skin discoloration, manifested by hyperpigmentation (excess pigmentation) on the palms and/or soles, was predominantly observed in non-Caucasian patients. The mechanism and clinical significance are unknown. It is recommended that all patients with HIV be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy. Emtriva is not indicated for the treatment of chronic HBV infection and the safety and efficacy of Emtriva have not been established in patients co-infected with HBV and HIV. "Flare-ups" of hepatitis B, where the illness can return in a worse way than before, have been reported in patients after the discontinuation of Emtriva. Patients co-infected with HIV and HBV should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment.
As with other NRTIs, Emtriva may cause lactic acidosis (buildup of an acid in the blood), serious liver problems called hepatotoxicity, with liver enlargement (hepatomegaly) and fat in the liver (steatosis).
Emtriva is a product of Gilead Sciences, Foster City, CA, USA.
Press Release from Gilead Sciences
U.S. FDA Approves Gilead Sciences' Emtriva, a One-Capsule, Once-Daily Medication for the Treatment of HIV
FOSTER CITY, Calif.--(BUSINESS WIRE)--July 2, 2003--
Gilead's Second HIV Therapeutic and Third AntiviralApproved in Two Years
Gilead Sciences today announced that the U.S. Food and Drug Administration (FDA) has cleared for marketing Emtriva(TM) (emtricitabine), a new 200 mg one-capsule, once-daily nucleoside reverse transcriptase inhibitor (NRTI) for the treatment of HIV infection in adults in combination with other antiretroviral medications. Emtriva has been evaluated in clinical trials of both treatment-naive and treatment-experienced HIV patients.
Emtriva attacks HIV by inhibiting reverse transcriptase, the enzyme that copies HIV RNA into new viral DNA. By interfering with this process, which is central to the replication of HIV, Emtriva 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.
"The drug's once-daily dosing, side effect profile and long half-life make it an important addition to a new generation of easier-to-use HIV therapies," said Michael Saag, MD, Professor of Medicine and Director of the HIV Clinic at the University of Alabama at Birmingham. "Its activity against the virus, combined with easy dosing, offers patients an effective treatment option that can help reduce the heavy pill burden often associated with combination therapy."
Emtriva is Gilead Sciences' second once-daily antiretroviral for the treatment of HIV. The compound was licensed from Emory University in 1996. Gilead's first anti-HIV medication, Viread(R) (tenofovir disoproxil fumarate), a one-tablet, once-daily nucleotide reverse transcriptase inhibitor (NtRTI), was cleared for marketing by the FDA in October 2001. The company is developing a fixed-dose co-formulation of Emtriva and Viread, which could potentially be available by early 2005. Emtriva is Gilead's third antiviral to receive FDA approval in less than two years, following Viread for HIV and Hepsera(R) (adefovir dipivoxil 10 mg) for chronic hepatitis B, and the seventh therapeutic in the company's portfolio.
"Emtriva is the latest example of Gilead's ongoing effort to reduce the impact of this disease -- and the burden of treatment -- on people infected with HIV. Both Emtriva and Viread are examples of new antiretrovirals with convenient dosing that can form the cornerstone of an effective once-daily treatment regimen," said John C. Martin, PhD, President and CEO of Gilead. "We extend our thanks to the many patients and healthcare professionals who participated in clinical trials of this important new therapy."
In the United States, the wholesaler acquisition cost for Emtriva is $252.83 for a bottle of 30 capsules, or one month of therapy. The drug will be available and shipped to wholesalers in the next week.
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 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. 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.
The Centers for Disease Control and Prevention (CDC) estimate that 950,000 Americans are infected with HIV, the virus that causes acquired immunodeficiency syndrome (AIDS). Approximately 360,000 infected individuals are receiving antiretroviral treatment for HIV infection in the United States today.
About Gilead
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 and regulatory agencies, including the European Medicines Evaluation Agency (EMEA), may not see advantages of Emtriva over lamivudine and may therefore be reluctant to prescribe or 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.
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