Three Studies Presented At 43rd EASL Showed Higher SVR For PEGASYS(R) (Peginterferon Alfa-2a) Plus Ribavirin Than Peginterferon Alfa-2b Plus Ribavirin

Main Category: Liver Disease / Hepatitis
Also Included In: Clinical Trials / Drug Trials;  Conferences;  Pharma Industry / Biotech Industry
Article Date: 27 Apr 2008 - 0:00 PDT

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Roche announced that new data from three studies indicate that chronic hepatitis C patients who received PEGASYS(R) (peginterferon alfa-2a) plus ribavirin had a greater chance of achieving a sustained virological response (SVR) than patients on peginterferon alfa-2b. Results from the studies were presented this week at the 43rd Annual Meeting of the European Association for the Study of the Liver (EASL) in Milan, Italy, adding to the robust body of evidence supporting PEGASYS as an effective treatment choice for treating patients with hepatitis C.

Ascione, et al: A Prospective, Randomized, Investigator-Initiated Head-to-Head Trial

Results of the Peginterferon Alpha-2a Plus Ribavirin Versus Peginterferon Alpha-2b Plus Ribavirin in Naive Patients with Chronic Hepatitis C Virus Infection Study: Results of a Prospective Randomized Trial, an independently-conducted study, were presented by Professor Antonio Ascione, Director of the Department of Gastroenterology Liver Unit at Cardarelli Hospital in Naples, Italy, in the oral late-breaker session at EASL. It is a prospective, randomized, investigator-initiated head-to-head trial designed to directly compare PEGASYS with peginterferon alfa-2b, each in combination with ribavirin. Enrolling 320 patients in Italy, of all genotypes, the study randomized patients to receive either PEGASYS 180 mcg/week or peginterferon alfa-2b 1.5 mcg/kg/week. Importantly, patients received equivalent starting doses of ribavirin (either 1,000 or 1,200 mg ribavirin per day based on body weight), and the process for ribavirin dose reduction was the same for all patients.

The results showed that overall 68.7 percent (110/186) of hepatitis C patients who were treated with PEGASYS achieved SVR, defined by undetectable hepatitis C virus (HCV) RNA in the blood 24 weeks after the end of treatment, compared to 54.4 percent (87/134) of patients who received peginterferon alfa-2b (p=0.008). Furthermore, in genotypes 1 and 4 -- the most difficult-to-treat patient group -- 51 patients (54.8 percent) taking PEGASYS achieved SVR, compared to 37 patients (39.8 percent) in the peginterferon alfa-2b group (p=0.04). In genotypes 2 and 3; 59 patients (88.1 percent) taking PEGASYS achieved SVR, compared to 50 patients (74.6 percent) taking peginterferon alfa-2b (p=0.046). Side effects were similar, although there were more withdrawals for side effects in the peginterferon alfa-2b group. (Please see below for complete safety information about PEGASYS and COPEGUS.)

T. Witthoeft, et al: Hepatitis C Treatment in Real-Life PRACTICE in Germany

Another study presented at EASL, a retrospective analysis called The PRACTICE Study, analyzed the response of 3,470 patients of all genotypes, to hepatitis C treatment between 2000 and 2007 in 23 German treatment centers with a high volume of patients. Patients were matched with regard to key baseline characteristics, including viral load, prior treatment history, body mass index, history of drug addiction, HIV co-infection as well as those who received a similar cumulative ribavirin dose. Among these matched pairs, significantly more patients treated with PEGASYS plus ribavirin achieved SVR compared to those treated with peginterferon alfa-2b and ribavirin (59.3 percent (N=848) vs. 53.0 percent (N=848) [p = 0.008]).

A. Craxi, et al: PROBE Compares The Pegylated Interferons

The PROBE study, an observational study, was designed to prospectively evaluate the efficacy of the pegylated interferons in real-life practice. The study enrolled 6,644 patients with genotype 1 virus at 167 treatment centers in Italy. The analysis included 1,351 patients of whom 887 received peginterferon alfa-2a and 464 received peginterferon alfa-2b. The study reflected "real-life" clinical settings by including patients with comorbidities, including obesity, diabetes, advanced age, psychiatric disorders, methadone use, thyreopathy and autoimmunity. Again, the trial found a greater chance of achieving SVR in patients treated with PEGASYS combination therapy compared to those treated with peginterferon alfa-2b combination therapy (SVR rates of 41 percent (360/887) vs. 34 percent (156/464), respectively [p = 0.004]).

"The outcomes of the three studies presented at EASL, comparing PEGASYS to peginterferon alfa-2b, contribute to a growing body of evidence that PEGASYS provides a successful outcome for many patients with hepatitis C," said Steven C. Sembler, vice president of Commercial Operations, Roche. "We are committed to further advancing the treatment of hepatitis C. Reflecting Roche's leadership in this area, our comprehensive clinical trials program aims to optimize treatment with PEGASYS and COPEGUS in the hope of bringing treatment success to even more patients."

Roche Comments on Schering-Plough "IDEAL" Study

Roche reiterated its position on the design of the Schering-Plough sponsored "IDEAL" study results, which were also presented at EASL. Clear biases in the design of this study that may have favored patients receiving peginterferon alfa-2b regimens prevent any direct comparison of the pegylated interferons. These biases include:

-- different ribavirin starting doses,

-- a different ribavirin dose reduction protocol, and

-- open label dosing for the PEGASYS arm.

IDEAL is a peginterferon alfa-2b dose-finding study that cannot answer which pegylated interferon is better.

About Hepatitis C

Hepatitis C is a blood-borne infectious disease of the liver and a leading cause of cirrhosis, liver cancer and the need for liver transplants. According to the Centers for Disease Control and Prevention (CDC), an estimated 4.1 million Americans (1.6 percent) have been infected with hepatitis C; 3.2 million are chronically infected. The number of new infections per year has declined from an average of 240,000 in the 1980s to about 26,000 in 2004. CDC estimates the number of hepatitis C-related deaths could increase to 38,000 annually by the year 2010, surpassing annual HIV/AIDS deaths.

About PEGASYS

PEGASYS, in combination with COPEGUS (ribavirin), is indicated for the treatment of adults with chronic hepatitis C who have compensated liver disease and have not previously been treated with interferon alpha. Efficacy has been demonstrated in patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A) and patients with HIV disease that are clinically stable (e.g., antiretroviral therapy not required or receiving stable antiretroviral therapy). In addition, PEGASYS in combination with COPEGUS is the first and only FDA-approved regimen for the treatment of chronic hepatitis C in patients coinfected with hepatitis C and HIV. PEGASYS is the only pegylated interferon indicated for the treatment of adult patients with chronic hepatitis B (HBeAg positive and HBeAg negative chronic hepatitis B who have compensated liver disease and evidence of viral replication and liver inflammation).

PEGASYS is dosed at 180mcg as a subcutaneous injection taken once a week. COPEGUS is available as a 200mg tablet, and is administered orally two times a day as a split dose. Roche has backed PEGASYS with the most extensive clinical research program ever undertaken in hepatitis C, with major studies initiated to advance treatment for hepatitis C patients with unmet needs, including patients co-infected with HIV and HCV, African Americans, patients with cirrhosis, and patients who have failed to respond to previous therapy.

IMPORTANT SAFETY INFORMATION

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 alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).

Alpha interferons, including PEGASYS(R) (Peginterferon alfa-2a), 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).

Use with Ribavirin. Ribavirin, including COPEGUS(R), may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen (see CONTRAINDICATIONS, WARNINGS, PRECAUTIONS and ADVERSE REACTIONS in complete product information).

PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and hepatic decompensation (Child-Pugh score greater than 6; class B and C) in cirrhotic CHC monoinfected patients before or during treatment. PEGASYS is also contraindicated in hepatic decompensation with Child-Pugh score greater than or equal to 6 in cirrhotic CHC patients coinfected with HIV before or during treatment. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).

COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus.

Chronic hepatitis C (CHC) patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alpha interferons, including PEGASYS. During treatment, patients' clinical status and hepatic function should be closely monitored, and PEGASYS treatment should be immediately discontinued if decompensation (Child-Pugh score greater than or equal to 6) is observed. Ischemic and hemorrhagic cerebrovascular events have been observed in patients treated with interferon alfa-based therapies, including PEGASYS. Events occurred in patients with few or no reported risk factors for stroke, including patients less than 45 years of age. Because these are spontaneous reports, estimates of frequency cannot be made and causal relationship between interferon alfa-based therapies and these events is difficult to establish.

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%).

Serious adverse events in hepatitis C trials included neuropsychiatric disorders (homicidal ideation, suicidal ideation, suicide attempt, suicide, psychotic disorder and hallucinations), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, supraventricular arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including idiopathic thrombocytopenic purpura, thrombotic thrombocytopenic purpura, psoriasis, lupus, rheumatoid arthritis and interstitial nephritis), 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). Adverse reactions reported during post-approval use of PEGASYS therapy, with and without ribavirin, include hearing impairment, hearing loss, serious skin reactions, including erythema multiforme major, and infections (bacterial, viral and fungal).

About Roche

Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2007 Roche was named Top Company of the Year by Med Ad News, one of the Top 20 Employers (Science) and ranked the No. 1 Company to Sell For (Selling Power). In previous years, Roche has been named as a Top Company for Older Workers (AARP) and one of the Best Companies to Work For in America (Fortune). For additional information about the U.S. pharmaceuticals business, visit our website http://www.rocheusa.com. Product and treatment information for U.S. healthcare professionals is available at http://www.RocheExchange.com.

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Roche
http://www.rocheusa.com

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