>>FOSTER CITY, Calif.--(BUSINESS WIRE)--Sept. 20, 2002-- -- Second novel Gilead antiviral approved in less than one year
Gilead Sciences (Nasdaq:GILD - News) today announced that it received U.S. Food and Drug Administration (FDA) approval for its antiviral agent Hepsera(TM) (adefovir dipivoxil) for the treatment of chronic hepatitis B. The drug will be shipped to wholesalers early next week.
Hepsera, administered as an oral 10 mg tablet, is the first nucleotide analogue to receive FDA approval for the treatment of chronic hepatitis B. It works by blocking the replication of the hepatitis B virus (HBV) in the body. In clinical studies, Hepsera treatment was associated with significant improvements in liver histology and fibrosis, reduction in serum HBV DNA levels, increased rates of seroconversion and normalization of alanine aminotransferase (ALT) levels as compared to placebo in treatment-naive patients and in patients with prior interferon experience. These pivotal studies included patients with compensated liver function and either "e" antigen-positive (HBeAg-positive) or "e" antigen-negative (HBeAg-negative, or precore mutant) chronic hepatitis B. Hepsera is the first drug for which efficacy has been demonstrated in HBeAg-negative patients in a 48-week double-blind, placebo-controlled study. The drug was studied and proven effective in patients who were treated with and developed resistance to lamivudine, including patients wait-listed for or who had received a liver transplant. Mutations associated with resistance to Hepsera have not been identified through 48 weeks of treatment in pivotal studies (n=467).
"Today's FDA approval of Hepsera gives physicians and their patients a new weapon in the fight against chronic hepatitis B," said Eugene Schiff, MD, Chief, Division of Hepatology and Director, Center for Liver Diseases, University of Miami, Florida. "Hepsera is an important development for people who have varying stages of active liver disease, including those with the HBeAg-negative or precore mutant strain of chronic hepatitis B. It is also an option for patients who aren't candidates for or have developed resistance to previously available therapies. With Hepsera, an unprecedented range of patients will have the potential to benefit from treatment."
"We extend our thanks to the more than 2000 patients and the health care professionals from around the world who participated in clinical studies of Hepsera, helping us to reach this important milestone today," said John C. Martin, PhD, President and CEO, Gilead Sciences. "Our mission at Gilead is to advance therapeutics for patients suffering from life-threatening infectious diseases, and we are proud to have developed a drug with the profile of Hepsera that will help to address the unmet medical needs of people living with chronic hepatitis B."
This is the second FDA approval for a novel Gilead antiviral in less than one year. Viread® (tenofovir disoproxil fumarate), the company's antiretroviral agent for the treatment of human immunodeficiency virus (HIV) infection, was approved in the United States in October 2001 and in the European Union in February 2002. In March 2002, Gilead submitted a Marketing Authorisation Application for adefovir dipivoxil for the treatment of chronic hepatitis B to the European Medicines Evaluation Agency. That application currently is under review.
Hepsera Indication
Hepsera is indicated for the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
This indication is based on histological, virological, biochemical and serological responses in adult patients with HBeAg-positive and HBeAg-negative chronic hepatitis B with compensated liver function, and in adult patients with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function.
Safety Profile
In clinical studies, the discontinuation rates and nature, severity and incidence of side effects and laboratory abnormalities were similar between people taking Hepsera and those taking placebo through 48 weeks. The most common adverse events observed in these studies were asthenia (weakness), headache, abdominal pain, nausea, flatulence, diarrhea and dyspepsia. These side effects were reported with similar frequency in Hepsera and placebo-treated patients. Through 48 weeks, no patients in the placebo-controlled studies had elevations in serum creatinine greater than or equal to 0.5 mg/dL from baseline. Four percent of patients receiving Hepsera and two percent of patients receiving placebo had increases greater than or equal to 0.3 mg/dL. With extended treatment beyond one year, two of 492 patients (less than one percent) had elevations in serum creatinine greater than or equal to 0.5 mg/dL from baseline and 29 of 492 had elevations greater than or equal to 0.3 mg/dL. These elevations resolved or remained unchanged with either continued treatment or discontinuation.
Additional adverse events reported in pre-and post-liver transplant patients include fever, vomiting, hepatic failure, increases in ALT and AST levels, abnormal liver function, increased cough, pharyngitis, sinusitis, pruritus, rash, increases in serum creatinine, renal failure and renal insufficiency. Thirteen percent of patients (41 of 324) developed an elevation in serum creatinine greater than or equal to 0.5 mg/dL from baseline and 26 percent developed an increase greater than or equal to 0.3 mg/dL through 48 weeks. The contribution of Hepsera to changes in serum creatinine is difficult to assess as the majority of these patients had some degree of underlying renal insufficiency at baseline and other risk factors for renal dysfunction during treatment. These patients should be carefully monitored and may require dose interval adjustments.
As is the case with other antiviral therapies for chronic hepatitis B, physicians need to monitor liver function for exacerbation of hepatitis following discontinuation of therapy. Additionally, HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection who receive anti-hepatitis B therapies that may have activity against HIV. 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.
About Hepatitis B
Hepatitis B is a serious disease that attacks the liver and can cause chronic (lifelong) infection, cirrhosis of the liver, liver cancer and death in up to a third of patients. In the United States, an estimated 1.25 million people are believed to have chronic hepatitis B, with approximately 100,000 new infections occurring annually. Worldwide, chronic hepatitis B is the leading cause of liver cancer and the tenth leading cause of death (approximately one million people will die this year from complications from the disease).
Hepatitis B is spread through infected blood or body fluids, sexual contact, injection drug use or perinatally from mother to child. Early symptoms include loss of appetite, fever, generalized aches and pains, fatigue, itching, urticaria (hives) and joint pain. Later symptoms may include nausea and vomiting, halitosis (bad breath), dark brown urine, jaundice (yellowing of the skin and eyes) and right-sided abdominal pain (especially with external pressure or palpitation).
Access to Hepsera
Gilead is committed to ensuring access to its products for patients most in need. Prior to regulatory approval of the drug, in March 2002, Gilead initiated an Early Access Program to provide Hepsera to patients in urgent need of a new treatment option for chronic hepatitis B. Similar programs are in place in Australia, Canada and many countries in Europe and will continue until the drug is commercially available in those areas.
In the United States, the wholesaler acquisition cost for Hepsera is $440.00 for a bottle of 30 tablets, or one month of therapy.
With today's FDA approval, and to further its commitment to helping all patients who can benefit from Hepsera, Gilead has established a U.S. Patient Assistance Program for people who do not have insurance or cannot afford to pay for treatment. For more information about the Patient Assistance Program or the Early Access Program, please call 1-800-GILEAD-5 or 1-650-574-3000.<<
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