| Hepatogastroenterology. 2003 May-Jun;50(51):775-8. |
Twice-a-day versus once-a-day interferon-beta therapy in chronic hepatitis C.
Kaito M, Yasui-Kawamura N, Iwasa M, Kobayashi Y, Nakagawa N, Fujita N, Ikoma J, Gabazza EC, Watanabe S, Adachi Y.
Third Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu-City, Mie, Japan 514-8507. kaitoma@clin.medic.mie-u.ac.jp
BACKGROUND/AIMS: The intravenous administration of interferon-beta may be effective for the treatment of chronic hepatitis C, as is intramuscular interferon-beta. We compared the efficacy and safety of twice-a-day versus once-a-day of natural interferon-beta for the initial treatment of patients with chronic hepatitis C. METHODOLOGY: Forty-nine patients with chronic hepatitis C, with less than 5 Meq/mL serum hepatitis C virus-RNA, were randomly assigned into one of the two treatment groups A and B and treated with natural interferon-beta following two different protocols. Twenty-two patients were treated with twice-a-day interferon-beta (3 MU) for 3 weeks followed by once-a-day interferon-beta (6 MU) for 5 weeks (group A), and 20 patients were treated with once-a-day interferon-beta (6 MU) for 8 weeks (group B). Seven patients did not complete the treatment protocol. Efficacy was assessed by measuring the serum levels of hepatitis C virus-RNA and aminotransferase. RESULTS: The rate of sustained virological response was significantly higher in group A (14 of 22 patients, 63.6%) than in group B (6 of 20 patients, 30.0%) (P < 0.05). Among patients with hepatitis C virus-RNA level less than 1 Meq/mL, the sustained virological response rate was significantly higher in group A (13 of 15 patients, 86.7%) than in group B (5 of 12 patients, 41.7%) (P < 0.05). However, the sustained virological response rate in patients with hepatitis C virus levels more than 1 Meq/mL was not significantly different between group A (1 of 7 patients, 14.3%) and group B (1 of 8 patients, 12.5%). CONCLUSIONS: Twice-a-day interferon-beta therapy is more effective than once-a-day interferon-beta for the treatment of chronic hepatitis C patients with hepatitis C virus-RNA levels less than 1 Meq/mL.
Roche has announced the European launch of an international trial to study the efficacy of Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin) in HCV-infected non responders who failed to respond to combination treatment with PEG-Intron (peginterferon alfa-2b) plus Rebetol (ribavirin).
Non-responders are patients who fail to achieve a sustained virological response and continue to have HCV present throughout their course of therapy.
Despite advances in the percentage of patients that can achieve a sustained virological response (or 'cure'), a study published in the Lancet in 2001 (1), demonstrates that 46% of patients who take peginterferon alfa-2b and ribavirin will not respond to it. Retreating these patients with an alternative regimen can result in a sustained virological response in a proportion of patients (2).
The trial is called
REPEAT, which stands for "REtreatment with PEGASYS in pATients
not responding to prior peginterferon alfa-2b/ribavirin combination
therapy." Nearly 1000 patients will enroll in the 72-week trial.
Until the launch of this study, all studies using pegylated interferon to
retreat non responders have measured themselves against conventional
interferon monotherapy and conventional interferon combination therapy.
However, these are not the therapies that the majority of patients receive
today. Now the standard of care is pegylated interferon and ribavirin and
most patients receive one of the two available pegylated interferon
combination therapies.
"The two pegylated interferons are different drugs, with different
properties and we know that Pegasys with Copegus has yielded impressive
results in hepatitis C patients,” said William M. Burns, head of the
pharmaceutical division at Roche. “We feel it is important for this pivotal
trial to show how Pegasys with Copegus can help that sizeable group of
patients who have not responded to the first pegylated interferon
combination therapy.”
The REPEAT study will evaluate the efficacy and safety of the
combination of Pegasys and Copegus given for a longer (72-week) period, as
well as examine the role of an induction regimen in this treatment-
resistant population. Patients in Europe, North America and Latin America
will participate in the study.
“We've already seen that Pegasys in combination with Copegus is a highly
effective treatment in treatment-naïve patients with some of the most
difficult-to-treat strains of the virus,” said the European lead study
investigator, Professor Patrick Marcellin, from the Hôpital Beaujon, France.
“Given this performance, Pegasys may prove to give these particular patients
another chance to respond and be cured.”
About Pegasys
Pegasys, a new generation hepatitis C therapy that is different by design,
provides significant benefit over conventional interferon therapy in
patients infected with HCV of all genotypes. The benefits of Pegasys are
derived from its new generation large 40-kilodalton branched-chain
polyethylene glycol (PEG) construction, which allows for constant viral
suppression over the course of a full
week. Pegasys also distributes more readily to the liver (the primary site
of infection) than conventional interferon.
Pegasys is the only pegylated interferon available as a ready-to-administer solution. Each weekly subcutaneous injection contains 180mcg of pegylated interferon alfa-2a, which is the approved dose for all patients, regardless of body weight.
About Roche
Roche is committed to the viral hepatitis disease area, having first
introduced Roferon-A for hepatitis B and then C, followed by Pegasys in
hepatitis C. Pegasys is also in phase III clinical development for patients
infected with HBV.
Roche has also launched its own brand of ribavirin, Copegus, to be used in conjunction with Roferon A or Pegasys. In addition, the company is developing levovirin, an alternative antiviral. Levovirin will be studied with the objective of demonstrating superior tolerability over ribavirin.
Roche manufactures and sells two tests used to detect the presence of HCV RNA in a person’s blood: the Amplicor HCV Test (v2.0) and the Amplicor HCV Monitor Test (v2.0) -
07/07/03
Source
References
1. MP Manns and others. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001; 358:958-65.
2. M Shiffman. Retreatment of Patients with Chronic Hepatitis C. Paper presented to the NIH Consensus Conference on the Management of Hepatitis C. 2002
Currently, interferon alfa and ribavirin are the mainstay of therapy for patients with chronic hepatitis C. Recently the pegylation of interferon has allowed once weekly dosing, resulting in an increased sustained viral response (SVR) rate and a better quality of life for patients.
The analysis of serum HCV dynamics has been shown useful in predicting clinical effects and optimizing the treatment regimen. The aim of the present study was to assess early serum HCV RNA changes in patients with chronic hepatitis C treated with PEG-Intron (peginterferon alfa-2b) plus ribavirin.
Male and female patients aged 18 to 65 years with chronic hepatitis C were eligible for the study. All patients received peginterferon alfa 2b 1.5 micrograms/kg once weekly for 4 weeks and then peginterferon alfa 2b 0.5 microgram/kg once weekly until the completion of the 48 week trial period, plus ribavirin orally with meals, adjusted to body weight. HCV RNA was determined at base-line, 48 hours, 4 and 12 weeks of therapy.
Data were obtained from 20 patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin; 16 male, 4 female, with a mean age of 44.4 +/- 11.9 years, 16 patients (80%) were infected with HCV genotype 1, the remainder were infected with genotype 2.
Mean baseline HCV RNA for the total group was 1,091,405 +/- 972,715 IU/mL. Mean reductions in viral load at 48 hours, 4 and 12 weeks for the 20 patients were 1.31 +/- 0.91 log, 1.99 +/- 1.27 log and 2.31 +/- 1.25 log, respectively.
A > 2 log reduction in HCV RNA was noticed in 12/20 patients (60%) at 4 weeks (early viral responders), in 9 of them (45%) HCV RNA was undetectable. This response in HCV RNA persisted at 12 weeks of therapy.
Early viral responders had a significant reduction in HCV RNA at 48 hours after the initial peginterferon alfa 2b injection (> 1 log reduction). Early viral response was observed in 8/16 patients with HCV genotype 1, and in all genotype 2 patients.
The authors conclude, “Treatment with peginterferon alfa 2b and ribavirin produces significant changes in the early HCV viral dynamics supporting the concept that such changes may be pivotal in achieving a sustained viral response.”
Department of Health
Sciences, Universidad Nacional Autonoma Metropolitana-Iztapalapa.
07/07/03
Source
Gallegos-Orozco
JF and others. Early HCV RNA changes in patients with chronic hepatitis C
treated with peginterferon alfa 2b and ribavirin.
Revista de investigacion
Clinica (Rev
Invest Clin). 55(2): 138-142. March-April 2003.
Effect of Ribavirin on Hepatitis C Viral Kinetics in Patients Treated with Pegylated Interferon
A dynamic equilibrium between viral production and clearance characterizes untreated chronic hepatitis C viral infection.
After initiating antiviral treatment, a typical multiphasic decay of viremia can be observed and analyzed using mathematical models. To elucidate the antiviral mechanism of ribavirin when used in combination with (pegylated) interferon alfa, researchers investigated kinetic parameters in patients with chronic hepatitis C treated with either Pegasys (peginterferon alfa-2a) with or without ribavirin and Intron A (standard interferon alfa-2b) plus ribavirin for 48 weeks.
Serum HCV RNA was measured frequently before, during, and at the end-of-treatment and the follow-up period. By using an appropriate model for viral dynamics, kinetic parameters were derived from nonlinear, least square fitting of serum HCV RNA quantifications.
The first phase of viral decay (day 1) and the second phase of viral decay (days 2 to 21) were similar for all treatment groups. After about 7 to 28 days, a third phase of viral decay was seen in several patients, and this phase of decay was significantly faster in patients treated with Pegasys plus ribavirin compared with those treated with Pegasys alone. The decay of this third phase was associated with the virologic end-of-treatment response and sustained virologic response.
Conclusion: The third-phase decay of initial viral kinetics, which may represent a treatment-enhanced degradation of infected cells, was more pronounced in patients treated with Pegasys plus ribavirin. This finding suggests that combination treatment leads to a better restoration of the patient's immune response.
06-04-03
Reference
E Herrmann and
others. Effect of ribavirin on hepatitis C viral kinetics in patients
treated with pegylated interferon. Hepatology 37(6): 1351-1358. June
2003.
News Search
Roche's Pegasys Effective To Treat Hepatitis C
-Studies
July 04, 2003 12:11 PM
GENEVA -(Dow Jones)- Swiss pharmaceutical company Roche Holding AG (Z.ROC) Friday presented new studies on its hepatitis-C drug Pegasys that underlined the efficacy of the treatment.
Among the key results from the studies was that 99% of Hepatitis C, or HCV, patients successfully treated with Pegasys are still virus-free up to four years after starting the treatment.
Hepatitis C affects some 170 million people worldwide and is the leading cause of liver cancer and cirrhosis in which healthy liver tissue is replaced by scar tissue. It is the number one reason for liver transplants in the U.S.
Another study concluded that 49% of cirrhosis patients treated with Pegasys achieved a sustained viral response when the drug was used in combination with Copegus.
For those cirrhotic patients with genotype 2/3 HCV, one of several strains of Hepatitis C, the rate of cure rose to 72% with the Pegasys combination therapy, a third study concluded. This compares to around 45% treated with conventional therapy.
Pegasys is a new generation Hepatitis C therapy that is different by design from conventional interferon therapy.
Roche launched the medication last year and sales are developing well. Sales of Pegasys were CHF120 million in the first quarter.
The Swiss pharmaceutical company has high hopes on this potential blockbuster drug, and expects the Hepatitis C market to expand.
The studies were presented at the 38th Annual Meeting of the European Association for the Study of the Liver, or EASL.
Company Web Site: http://www.roche.com
-By Anita Greil, Dow Jones Newswires; +41 1 211 6588; anita.greil@dowjones.com
Corrected July 4, 2003 12:11 ET (16:11 GMT)
(END) Dow Jones Newswires
07-04-03 0815ET
Among the key results from the studies was that 99% of Hepatitis C, or HCV, patients successfully treated with Pegasys are still virus-free up to four years after starting the treatment.
(In an item that ran at 1200 GMT, the word "sucessfully" was omitted when referring to the patients with Pegasys.)
(END) Dow Jones Newswires
Roche says
new data underscores power of Pegasys
Reuters,
07.04.03, 8:01 AM ET
LONDON,
July 4 (Reuters) - Switzerland's Roche Holding AG said on Friday new
clinical data showed its new hepatitis C drug Pegasys offered long-term
protection in even difficult-to-treat patients with serious liver disease.
A
large analysis of patients with liver cirrhosis, presented at the annual
meeting of the European Association for the Study of the Liver in Geneva,
showed 49 percent achieved sustained reduction in virus when given a
combination of Pegasys and Roche's ribavirin drug Copegus.
A
second study showed more than 99 percent of all Pegasys patients who had
been successfully treated remained virus-free up to four years later.
Roche said a possible explanation for the effectiveness of Pegasys was
that levels of the drug remained constant in the body over a seven-day
period.
By
contrast, half of patients treated with Schering-Plough Corp's (nyse:
SGP -
news -
people)
Peg-Intron had no detectable drug in their bodies by the fifth day after
an injection, which could potentially lead to renewed virus replication,
it said.
Roche added it was launching a a global trial to study the efficacy of
Pegasys plus Copegus in patients who failed to respond to Peg-Intron and
ribavirin.
Pegasys, which was launched at the end of last year, is Roche's biggest
new drug in years.
The
company said last week that early demand had proved stronger than expected
and it might revise up its current peak sales forecast for the product of
1.5 billion Swiss francs ($1.11 billion).
Copyright 2003, Reuters News Service
07-04-03 1220ET