November 18, 2004
European CHMP Gives Positive Opinion on Gilead's Truvada as Part of Combination HIV Therapy
Truvada(TM) Combines Anti-HIV Drugs Emtriva(R) and Viread(R) in One Tablet Dosed Once A Day
FOSTER CITY, Calif.--(BUSINESS WIRE)--Nov. 18, 2004-- Gilead Sciences, Inc. (Nasdaq:GILD) today announced that the European Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), has recommended granting a Marketing Authorisation for Truvada(TM) (emtricitabine and tenofovir disoproxil fumarate) in the 25 member states of the European Union. The European Commission generally follows the CHMP recommendation and grants a final Marketing Authorisation within a few months following a positive recommendation. Truvada combines Emtriva(R) (emtricitabine) and Viread(R) (tenofovir disoproxil fumarate) in one tablet taken once a day in combination with other antiretroviral agents.
The CHMP recommended indication for Truvada is for the treatment of HIV-infected adults in combination with other antiretroviral agents. This indication is based on the demonstration of the benefit of the combination of emtricitabine and tenofovir disoproxil fumarate in antiretroviral therapy in treatment-naive patients. As Truvada contains emtricitabine and tenofovir disoproxil fumarate, the guidance for physicians in the Truvada Summary of Product Characteristics (SmPC) is consistent with the guidance in the SmPC of Emtriva and Viread.
"For many patients, combination therapy can mean adhering to drug regimens that involve multiple daily pills with dosing requirements that vary," said Brian Gazzard, MD, Clinical Research Director, Chelsea and Westminster Hospital, London. "Truvada joins two of the drugs needed for triple-drug therapy into a single once-a-day tablet, making it an important new treatment option for patients, who must take a combination of drugs to combat the virus."
Gilead submitted a Marketing Authorisation Application (MAA) for Truvada on March 12, 2004 under the centralized procedure. The positive opinion for Truvada is the fourth positive recommendation Gilead has received from the Committee for an antiviral treatment in three years.
"We are pleased to receive a positive opinion from the CHMP for Truvada," said John C. Martin, PhD, President and CEO of Gilead Sciences. "We look forward to our continued work with the EMEA to make this combination product available to people living with HIV/AIDS throughout Europe."
The U.S. Food and Drug Administration (FDA) granted marketing approval to Truvada in the United States on August 2, 2004. The U.S. Department of Health and Human Services (DHHS) Guidelines for the Use of Antiretroviral Agents recommend Truvada's component drugs, Viread and Emtriva, as a first line dual nucleoside reverse transcriptase inhibitor (NRTI) backbone in combination with a non-nucleoside reverse transcriptase inhibitor (NNRTI) for adults infected with HIV.
Important Safety Information from U.S. Prescribing 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. Viread, Emtriva and Truvada are not indicated for the treatment of chronic hepatitis B virus (HBV) infection and the safety and efficacy of these drugs has 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 Viread, Emtriva or Truvada 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 Viread, Emtriva, Truvada and other anti-HIV medicines. The cause and long term health effect of these conditions are unknown.
It is important that patients be aware that HIV medications must be taken as part of combination regimens and do not cure HIV infection, nor do they reduce its transmission.
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. Safety and efficacy studies using Truvada tablets or using Emtriva and Viread in combination are ongoing.
Both components of Truvada have been studied individually, as part of multi-drug regimens and have been found to be safe and effective. Since Emtriva and lamivudine (3TC) are comparable in their structure, resistance profiles, and efficacy and safety as part of multi-drug regimens, existing data from the use of lamivudine and Viread in combination have been extrapolated to support use of Truvada tablets for the treatment of HIV-1 infection in adults. Therefore, in treatment-naive patients, Truvada should be considered as an alternative to the combination of Viread and lamivudine for those patients who might benefit from a once-daily regimen. In treatment-experienced patients, the use of Truvada should be guided by laboratory testing and treatment history.
There are no study results demonstrating the effect of Truvada on clinical progression of HIV-1, and it is not recommended that Truvada be used as a component of a triple nucleoside regimen.
Truvada should not be used with Emtriva or Viread, or other drugs containing lamivudine, including Combivir(R), Epivir(R), Epivir-HBV(R), Epzicom(TM) or Trizivir(R). Two-hundred eighty-three patients have received combination therapy with Emtriva and Viread with either a non-nucleoside reverse transcriptase inhibitor or protease inhibitor for 24 to 48 weeks in ongoing clinical studies. Based on these limited data, no new patterns of adverse events were identified and there was no increased frequency of established toxicities. 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. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of Viread in treatment-naive adults and in treatment-experienced adults. There are no study results demonstrating the effect of Viread on clinical progression of HIV-1. The use of Viread should be considered for treating adult patients with HIV-1 strains that are expected to be susceptible to tenofovir as assessed by laboratory testing or treatment history.
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 or 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 serious cases, has 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. 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. The most common adverse events and those occurring in more than 5 percent of patients receiving Viread with other antiretroviral agents in clinical trials include asthenia, pain, abdominal pain, headache, nausea, diarrhea, vomiting, rash (rash, pruritis, maculopapular rash, urticaria, vesiculobullous rash and pustular rash), flatulence, dizziness and depression. Less than 1 percent of patients discontinued participation because of gastrointestinal events.
In the United States, Emtriva is indicated, in combination with other antiretroviral agents, for the treatment of HIV-1 infection in adults. 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.
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 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. These risks include that the CHMP opinion is not binding upon the European Commission, the European Commission may delay approval beyond early 2005 and Truvada remains an investigational compound in the European Union pending granting of the Marketing Authorisation. 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, 2003 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.
Truvada is a trademark and Viread and Emtriva are registered trademarks of Gilead Sciences, Inc.
For more information on Truvada, please call the Gilead Public Affairs Department at 1-800-GILEAD-5 (1-800-445-3235) or visit www.gilead.com.
CONTACT: Gilead Sciences, Inc.
Susan Hubbard, 650-522-5715 (Investors)
James Loduca, 650-522-5908 (Media)
SOURCE: Gilead Sciences, Inc.