FDA Approves Pegasys as the First and Only Pegylated Interferon for the Treatment of Chronic Hepatitis B
In a widely anticipated action, the US Food and Drug Administration (FDA) has approved peginterferon alfa-2a (Pegasys) for the treatment of chronic hepatitis B (CHB). Pegasys is already FDA-approved for the treatment of chronic hepatitis C infection (CHC).
The FDA action makes Pegasys the first and only pegylated interferon approved for the treatment of CHB, including for individuals who are hepatitis B 揺?antigen positive (HBeAg-positive) and hepatitis B 揺?antigen-negative (HBeAg-negative).
Following are excerpts from the approval announcement by Roche Pharmaceuticals (Roche):
揅hronic hepatitis B infection is a serious disease that causes more than 5,000 deaths in the United States each year,?said Salvatore Badalamenti, M.D., Medical Director, Roche. 揚egasys now offers hepatitis B patients a treatment option that is taken for a fixed duration of 48 weeks with the goal of providing a lasting response after treatment is completed.?/span>
The US Centers for Disease Control and Prevention estimates that 1.25 million people in the United States are chronically infected with hepatitis B. Chronic hepatitis B can lead to cirrhosis, hepatocellular carcinoma and death.
揟his approval provides another important option for the treatment of hepatitis B,?said Frederick G. Thompson, President and CEO of The American Liver Foundation. 揥e commend Roche for its extensive research and commitment to treating people with chronic liver diseases.?/span>
Pegasys has a dual mode of action; it slows replication of the hepatitis B virus and boosts the immune system.
Pivotal Studies
The two large-scale multinational phase III trials, in more than 1,500 patients with both the HBeAg-positive and HBeAg-negative variations of chronic hepatitis B, demonstrated that 24 weeks after a defined 48 week period of therapy, more patients achieved a sustained response with Pegasys than with lamivudine (Epivir-HBV). These studies demonstrated that the addition of lamivudine to Pegasys did not improve response rates over Pegasys alone.
Specifically, hepatitis B patients treated with Pegasys had higher rates of:
- HBV seroconversion in HBeAg positive patients (32% Pegasys vs. 19% lamivudine)
- HBV DNA response (32% Pegasys vs. 22% lamivudine in HBeAg positive patients and 43% Pegasys vs. 29% lamivudine in HBeAg negative patients)
- ALT normalization in HBeAg negative patients (59% Pegasys vs. 44% lamivudine)
Conclusions regarding comparative efficacy of Pegasys and lamivudine treatment based upon the end of follow-up results are limited by the different mechanisms of action of the two compounds. Most treatment effects of lamivudine are unlikely to persist 24 weeks after therapy is withdrawn, according to Roche.
Recent results from a long-term follow up study presented at the 40th annual meeting of the European Association for the Study of the Liver (40th EASL, April 13-17) indicate that patients with HBeAg-negative chronic hepatitis B who responded to treatment with Pegasys maintained the benefit for at least a year after treatment.
The phase III study results in individuals with HBeAg-negative chronic hepatitis B? were published in the September 2004 in the New England Journal of Medicine. The results of the phase III study in patients with HBeAg-positive chronic hepatitis B were presented at the 40th EASL.
Lead investigators of both studies stated that the results of the trials warrant Pegasys becoming a first-line treatment for HBeAg-positive and HBeAg-negative chronic hepatitis B.
Roche was granted approval by the EU Commission in late February 2005 to market Pegasys for the treatment of chronic hepatitis B.
About Chronic Hepatitis B
In the US the most common modes of transmission of the hepatitis B virus are through sexual and blood-to-blood contact, although the disease can also be transmitted from pregnant women to their infants. The number of new infections in the US has decreased in recent years, in part due to the introduction of the hepatitis B vaccine in 1982.
Almost all (90-95 percent) adults who contract hepatitis B clear the virus from their systems within a few months and develop immunity. The remainder of the infections become chronic, which is when the virus stays in the blood, infecting liver cells and possibly damaging them.
Facts about Pegasys (Peginterferon Alfa-2a)
PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alfa. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that is clinically stable (eg, antiretroviral therapy not required or receiving stable antiretroviral therapy). Pegasys is indicated for the treatment of adult patients with HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation.
Adverse Effects
Alpha interferons, including Pegasys, may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions.
In many, but not all cases, these disorders resolve after stopping Pegasys therapy (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information for Pegasys) .
The adverse event profile of hepatitis B patients treated with Pegasys was generally similar to that shown for hepatitis C patients treated with Pegasys monotherapy except for exacerbations of hepatitis.
Serious adverse events included neuropsychiatric disorders (suicidal ideation and suicide attempt), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including thrombotic thrombocytopenic purpura, psoriasis and lupus), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).
Recent HIV and Hepatitis.com Articles on Pegasys for Chronic Hepatitis B:
Peginterferon Alfa-2a (Pegasys) Produces a Sustained Response in HBeAg-negative HBV Patients One Year after the End of Treatment - 4/25/05
Factors Predicting Response to Pegylated Interferon in HBeAg Positive Chronic Hepatitis B - 4/22/05
Peginterferon Alfa-2a (Pegasys) Versus Peginterferon Alfa-2a Plus Lamivudine Versus Lamivudine Alone In HBeAg Positive Chronic HBV - 4/18/05
Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with HBeAg-Negative Chronic Hepatitis B - 9/17/04
Other HIV and Hepatitis.com Articles on Pegasys for Chronic Hepatitis B:
Factors Predicting Response to Pegylated Interferon in HBeAg Positive Chronic Hepatitis B - 4/22/05
Peginterferon Alfa Is Effective in Almost One-third of Patients Who Failed Previous Treatment with Standard Interferon or Lamivudine - 11/17/04
Patients with Chronic Hepatitis B Have Better Safety and Quality of Life When Treated with Peginterferon Alfa-2a (Pegasys) Monotherapy Compared to Those with Chronic Hepatitis C 11/01/04
Current Treatments for Hepatitis B: An Overview - 10/25/04
Peginterferon Alfa-2a Alone, Lamivudine Alone, and the Two in Combination in Patients with HBeAg-Negative Chronic Hepatitis B 09/17/04
Pegasys Monotherapy Produces Significantly Higher Sustained Response Rates (SVR) Compared to Epivir-HBV 04/30/04
A New Bio-Mathematical Model Describes the Dynamics of HBV-DNA and Infected Hepatocytes in Patients Treated with Peginterferon alfa-2a Monotherapy, Lamivudine or Peginterferon Alfa-2a (Pegasys) Plus Lamivudine (Epivir-HBV) 04/21/04
Peginterferon Alfa-2a (Pegasys) Monotherapy is More Effective Than Lamivudine (Epivir-HBV) Monotherapy for HBeAg-negative Chronic HBV Patients 04/21/04
Pegasys Is a Promising Therapy for Chronic Hepatitis B 01/23/04
Pegasys Found More Effective Than Epivir-HBV in Treatment of Most Difficult to Treat Patients with Chronic Hepatitis B 10/31/03
Treatment of Chronic Hepatitis B with Pegasys Shows Improved Response Rate Compared to Roferon 01/08/03
05/16/05
Source
Roche Pharmaceuticals. FDA Approves Pegasys as the First and Only Pegylated Interferon for the Treatment of Chronic Hepatitis B. Press Release. May 13, 2005. | 
发表于 2005-5-31 03:29
