March 15, 2004
Gilead Submits Applications to U.S. and European Regulatory Authorities for Fixed Dose Co-Formulation of Viread and Emtriva
FOSTER CITY, Calif.--(BUSINESS WIRE)--March 15, 2004-- New Product Will Combine Two Anti-HIV Drugs in One Pill Taken Once Daily
Gilead Sciences, Inc. (Nasdaq:GILD) today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for marketing approval of a fixed dose co-formulation of the company's anti-HIV medications Viread(R) (tenofovir disoproxil fumarate) and Emtriva(TM) (emtricitabine). The proposed co-formulation combines Viread and Emtriva in a single pill dosed once daily, to be taken in combination with other antiretrovirals for the treatment of HIV.
The company also announced the submission of its Marketing Authorisation Application (MAA) for the fixed dose co-formulation to the European Agency for the Evaluation of Medicinal Products (EMEA). Review of the MAA will be coordinated by the EMEA under the centralized licensing procedure, which, when finalized, provides one marketing authorization in all 25 member states of the enlarged European Union.
"There is a need to simplify HIV drug regimens in order to improve patient quality of life and adherence to therapy," said John C. Martin, PhD, President and Chief Executive Officer, Gilead Sciences. "Recent advances in the development of efficacious, well-tolerated and conveniently dosed medications are helping make HIV regimens easier to manage. We believe that the co-formulation of once-daily Viread and Emtriva may help further reduce the treatment burden on patients and improve adherence."
Each co-formulated tablet will contain 300 mg of tenofovir disoproxil fumarate (Viread) and 200 mg of emtricitabine (Emtriva). Viread, the first nucleotide reverse transcriptase inhibitor (NtRTI) approved for HIV combination therapy, was cleared for marketing by the FDA in 2001 and by the EMEA in 2002. It is available as a single 300 mg tablet taken once daily. Emtriva is a nucleoside reverse transcriptase inhibitor (NRTI) for HIV cleared for marketing by the FDA and EMEA in 2003. It is available as a single 200 mg capsule that is also taken once daily. Both medications work by blocking reverse transcriptase, an enzyme crucial for HIV replication. Following the potential approval of the fixed dose co-formulation, each drug will continue to be sold individually.
"Research indicates that for antiretroviral therapy to be successful, patients need to adhere to their drug regimens at least 95 percent of the time," said Anton Pozniak, MD, treating physician and HIV specialist at Chelsea and Westminster Hospital in London. "Patients are more likely to comply with treatment when they receive regimens with a favorable side effect profile that are conveniently dosed. If approved, Gilead's co-formulation of Viread and Emtriva will be an important addition to the treatment armamentarium for physicians and patients."
In the United States and Europe, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Assessment of adverse reactions, as described in the U.S. package insert, is based on one study of treatment-experienced patients and one study of treatment-naive patients. In Study 907, a total of 550 treatment-experienced patients received treatment with Viread 300 mg (n=368) or placebo (n=182) for 24 weeks followed by extended treatment with the drug. In Study 903, a total of 600 patients received treatment with Viread (n=299) or stavudine (n=301) in combination with lamivudine and efavirenz for 48 weeks. The most common adverse events in these patients were dizziness and mild to moderate gastrointestinal events, such as nausea, diarrhea, vomiting and flatulence.
In clinical practice, a number of adverse events, including renal impairment, nausea, rash and asthenia (weakness) have 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. 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 the hepatitis B virus, exacerbations of hepatitis B have been reported in patients after discontinuation of Viread. Decreases in bone mineral density (BMD) at the lumbar spine and hip 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.
In the United States, Emtriva is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. In the European Union, Emtriva is indicated in combination with other antiretroviral agents for the treatment of HIV in adults and children. In addition to the standard 200 mg capsule taken once daily for use in adults, in the European Union it is also approved 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.
Assessment of adverse events, as described in the U.S. 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.
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 six 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 that regulatory authorities in the United States or Europe may not accept the filing for review, may require more or different data to complete the application, or may ultimately determine that the application does not support approval of the fixed dose co-formulation of Viread and Emtriva. For example, our filings contain extensive data on the single agents but only limited data on the fixed dose co-formulation. We cannot be certain that either the FDA or the EMEA will accept our filing for review or ultimately approve the fixed dose co-formulation without additional data on the fixed dose co-formulation. 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, 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.
Viread is a registered trademark and Emtriva is a trademark of Gilead Sciences, Inc.
For complete prescribing information, please visit www.viread.com or www.emtriva.com.
For more information on Gilead Sciences, please visit the company's web site at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
CONTACT: Gilead Sciences, Inc. Susan Hubbard, 650-522-5715 (Investors) James Loduca, 650-522-5908 (Media) www.gilead.com SOURCE: Gilead Sciences, Inc.