March 08, 2006
U.S. FDA Grants Traditional Approval for Gilead's Once-Daily HIV Medications Truvada(R) and Viread(R); 48-Week Data from Pivotal Study 934 Added to U.S. Prescribing Information for Both Products
FOSTER CITY, Calif.--(BUSINESS WIRE)--March 8, 2006--Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the U.S. Food and Drug Administration (FDA) has granted traditional approval status to its once-daily antiretroviral Viread(R) (tenofovir disoproxil fumarate) and its fixed-dose product Truvada(R) (emtricitabine and tenofovir disoproxil fumarate), which combines the company's two antiretrovirals Emtriva(R) (emtricitabine) and Viread in a single daily tablet. Traditional approval status was granted following FDA review of 48-week data from Study 934, the second confirmatory pivotal study for Viread. The FDA previously granted accelerated approval for Viread and Truvada in October 2001 and August 2004, respectively.
As part of traditional approval, the U.S. prescribing information for Viread and Truvada now include 48-week data from Study 934, a Phase III open-label trial comparing a once-daily regimen of Viread, Emtriva and efavirenz to twice-daily Combivir(R) (lamivudine/zidovudine) and once-daily efavirenz in treatment-naive patients. Eighty-four percent of patients in the Viread/Emtriva group compared to 73 percent of patients in the Combivir group achieved and maintained HIV RNA less than 400 copies/mL through week 48. This difference largely results from the higher number of discontinuations in the Combivir group due to adverse events (9 percent vs. 4 percent in the Viread/Emtriva group) and other reasons including lost to follow-up, patient withdrawal, noncompliance and protocol violation (14 percent vs. 10 percent in the Viread/Emtriva group). In addition, 80 and 70 percent of patients in the Viread/Emtriva group and the Combivir group, respectively, achieved and maintained HIV RNA less than 50 copies/mL. The mean increase in CD4 cell count was 190 cells/mm3 in the Viread/Emtriva group and 158 cells/mm(3) in the Combivir group. The 48-week data in the label reflect those which were published in the January 19, 2006 issue of New England Journal of Medicine.
"In the United States, Truvada is now the most-prescribed antiretroviral of its class and its use is quickly growing in the European Union, where it was more recently made available," said Kevin Young, Executive Vice President, Commercial Operations, Gilead Sciences. "We look forward to continuing to generate and share important data from ongoing clinical studies to help further define the profile of our products for the medical community."
Guidelines issued by the U.S. Department of Health and Human Services (DHHS) list emtricitabine and tenofovir disoproxil fumarate as preferred agents for use as part of a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in appropriate patients who have never taken anti-HIV medicines before.
Gilead and Bristol-Myers Squibb have established a U.S. joint venture to produce a once-daily fixed-dose product containing Truvada and efavirenz and expect to file a new drug application with the FDA in the second quarter of this year. If approved by the FDA, the new product would be the first and only complete Highly Active Antiretroviral Therapy (HAART) regimen for HIV available in a single once-daily fixed-dose tablet. The U.S. joint venture to develop and commercialize the fixed-dose regimen of Truvada and efavirenz is the first of its kind in the field of HIV treatment.
It is important that patients be aware that individual HIV medications must be taken as part of combination regimens, and that they do not cure HIV infection or prevent transmitting HIV to other people.
2006 marks the 25th anniversary of the start of the AIDS epidemic. The first cases of HIV/AIDS were reported by the U.S. Centers for Disease Control and Prevention (CDC) in the June 5, 1981 issue of the Morbidity and Mortality Weekly Report (MMWR). Today, CDC estimates that more than one million Americans are infected with HIV, the virus that causes AIDS. Of these, approximately 25 percent are unaware of their infection. Although HIV treatment options have expanded rapidly in recent years, CDC estimates that 216,000 Americans who are HIV infected and eligible for antiretroviral treatment are currently not receiving it.
Ensuring Access in Developing Countries
The parent compound of Viread was discovered through a collaborative research effort between Dr. Antonin Holy, Institute for Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic (IOCB) in Prague and Dr. Erik DeClercq, Rega Institute for Medical Research, Katholic University in Leuven, Belgium. The inventors have agreed to waive their right to a royalty on sales of products containing tenofovir in the 97 developing countries served by the Gilead Access Program to ensure the product can be offered at a no-profit price in parts of the world where the AIDS epidemic has hit the hardest.
Important Safety Information for Truvada, Viread and Emtriva
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. Truvada, Viread and Emtriva are not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of these drugs have not been established in patients co-infected with HBV and HIV. Severe acute exacerbations of hepatitis B have been reported in patients who have discontinued Viread or Emtriva. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue Truvada, Viread or Emtriva and are co-infected with HIV and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Changes in body fat have been observed in patients taking Truvada, Viread and Emtriva and other anti-HIV medicines. The cause and long-term health effect of these conditions are unknown. Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including Truvada, Emtriva and Viread.
Truvada is a fixed-dose combination product that combines 200 mg of Emtriva and 300 mg of Viread in one tablet, taken once a day. In the United States, Truvada is indicated in combination with other antiretroviral agents (such as non-nucleoside reverse transcriptase inhibitors or protease inhibitors) for the treatment of HIV-1 infection in adults. Truvada should not be coadministered with Emtriva, Viread or lamivudine-containing products and it is not recommended that Truvada be used as a component of a triple nucleoside regimen. In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
Clinical study 934 supports the use of Truvada tablets for the treatment of HIV-1 infection. Additional data in support of the use of Truvada are derived from study 903, in which Viread and lamivudine were used in combination in treatment-naive adults, and clinical study 303, in which Emtriva and lamivudine demonstrated comparable efficacy, safety and resistance patterns as part of multidrug regimens.
No drug interaction studies have been conducted using Truvada. Drug interactions have been observed when didanosine, atazanavir, or lopinavir/ritonavir are co-administered with Viread, a component of Truvada, and dose adjustments may be necessary. Data are not available to recommend a dose adjustment of didanosine for patients weighing less than 60 kg. Patients on atazanavir and lopinavir/ritonavir plus Truvada should be monitored for Truvada-associated adverse events that may require discontinuation. When co-administered with Viread, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.
Four-hundred and forty-seven HIV-1 infected patients have received combination therapy with Emtriva and Viread with either a non-nucleoside reverse transcriptase inhibitor (Study 934) or protease inhibitor for 48 weeks in clinical studies. Adverse events observed in Study 934 were generally consistent with those seen in other studies in treatment-experienced or treatment-naive patients receiving Viread and/or Emtriva. Adverse events observed in more than five percent of patients in the Viread/Emtriva group in Study 934 include diarrhea, nausea, fatigue, headache, dizziness and rash.
United States Full Prescribing Information is available at www.truvada.com. For additional safety information about Emtriva or Viread in combination with other antiretroviral agents, please see "About Emtriva" and "About Viread," below.
In the United States, Viread is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. Viread should not be used in combination with Truvada.
Drug interactions have been observed when didanosine, atazanavir or lopinavir/ritonavir is co-administered with Viread and dose adjustments may be necessary. Data are not available to recommend a dose adjustment of didanosine for patients weighing less than 60 kg. Patients on atazanavir and lopinavir/ritonavir plus Viread should be monitored for Viread-associated adverse events, which may require discontinuation. When co-administered with Viread, it is recommended that atazanavir 300 mg be given with ritonavir 100 mg. Atazanavir without ritonavir should not be co-administered with Viread.
Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), has been reported among patients taking Viread. 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. Decreases in bone mineral density (BMD) at the lumbar spine and hip have been seen with the use of Viread. The effects of Viread-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk are unknown. The most common adverse events among patients receiving Viread with other antiretroviral agents in clinical trials were mild to moderate gastrointestinal events and dizziness. Moderate to severe adverse events occurring in more than 5 percent of patients receiving Viread included rash (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash and pustular rash), headache, pain, diarrhea, depression, back pain, fever, nausea, abdominal pain, asthenia and anxiety (Study 903). Less than 1 percent of patients discontinued participation because of gastrointestinal events (Study 907).
United States Full Prescribing Information is available at www.viread.com.
In the United States, Emtriva is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in patients over three months of age. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts from controlled studies of 48 weeks duration in antiretroviral-naive patients and antiretroviral-treatment-experienced patients who were virologically suppressed on an HIV treatment regimen. 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.
Adverse events that occurred in more than 5 percent of patients receiving Emtriva with other antiretroviral agents in clinical trials include abdominal pain, asthenia (weakness), headache, diarrhea, nausea, vomiting, dizziness and rash (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash, pustular rash and allergic reaction). Approximately 1 percent of patients discontinued participation because of 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 on the palms and/or soles, was generally mild and asymptomatic. The mechanism and clinical significance are unknown. For pediatric patients over three months of age, the adverse event profile observed during clinical trials was similar to that of adult patients, with the exception of anemia and a higher frequency of hyperpigmentation.
United States Full Prescribing Information is available at www.emtriva.com.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North America, 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 the risk that the safety and efficacy data obtained through 48 weeks of Study 934 will not be observed in other studies or clinical practice and risks associated with the development and approval of the fixed-dose combination product containing Truvada and Sustiva. 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, 2004 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.
For full prescribing information, please visit www.Truvada.com, www.Viread.com and www.Emtriva.com.
Truvada, Viread and Emtriva are registered trademarks of Gilead Sciences, Inc.
For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call
Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
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SOURCE: Gilead Sciences, Inc.