The aim of the current Dutch study was to test re-treatment of chronic hepatitis C patients with virologic relapse (VR).

Thirty-seven chronic hepatitis C patients with virological relapse (VR) after previous interferon-alfa (IFN) or IFN/ribavirin (Riba) therapy, were re-treated. Patients were randomized for either IFN/Riba and amantadine (Ama) including a 2-week initial high IFN induction course (18 MU IFN daily) (group A) or the same 2-week IFN induction course combined with Riba/Ama, followed by Riba/Ama without IFN (group B).

Treatment duration for both groups was 24 weeks with a 24-week follow-up thereafter.

The inclusion in group B was prematurely stopped because all patients (n = 10) relapsed within 2 weeks after stopping IFN. Therefore, all subsequent patients were included in group A (n = 27).

In group A, 44% achieved a sustained virological response (SVR) and 29% of the patients with an end-of-treatment virological response had a VR again.

Of all pretreatment characteristics, only genotype non-1 patients had a significantly higher chance of achieving SVR (P < 0.001).

Of the characteristics during treatment only a negative hepatitis C virus (HCV)-RNA test result in transcription-mediated amplification (TMA) at week 6 had a high predictive value for SVR, 80% in all patients and 92% in genotype non-1 patients.

The authors conclude, “Hepatitis C patients with a VR to previous antiviral treatment can be successfully re-treated with IFN induction combined with Riba/Ama for only 6 months, when they have genotype non-1 and a negative HCV-RNA test result in TMA 6 weeks after the start of therapy. Riba/Ama combination therapy without IFN does not prevent VR after 2 weeks high IFN induction.”

08/04/03

Reference
CJ Weegink and others. Chronic hepatitis C patients with a post-treatment virological relapse re-treated with an induction dose of 18 MU interferon-alpha in combination with ribavirin and amantadine: a two-arm randomized pilot study. Journal of Viral Hepatitis 10(3): 174-82. May 2003.

Ten interferon-naïve patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microgram/kg peginterferon alfa-2b once (group A) or twice weekly (group B) for 4 weeks.

Viral load and serum concentrations of peginterferon alfa-2b were measured. Peginterferon alfa-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, peginterferon alfa-2b was undetectable in nine patients in group A (once weekly dosing).

The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) peginterferon alfa-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of peginterferon alfa-2b, but increased again on day 3.

In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001).

The authors conclude, “To achieve continuous drug exposure and to improve initial viral clearance, peginterferon alfa-2b has to be given at least two times weekly.”

08/04/03

Reference
E Formann and others. Journal of Viral Hepatitis 10(4): 271-277. July 2003.

DGNews

Hepatitis C Virus Drug Pegintron (Peginterferon Alfa-2b) Should To Be Given Twice Weekly

Hepatitis C Virus Drug Pegintron (Peginterferon Alfa-2b) Should To Be Given Twice Weekly

VIENNA, AUSTRIA -- July 29, 2003 -- A study published in the July issue of the Journal of Viral Hepatitis(1) shows that the currently prescribed once weekly dosing schedule of peginterferon alfa-2b (PegIntron™-Schering-Plough) does not provide sustained suppression of the hepatitis C virus (HCV). The study found that to achieve continuous drug exposure and to improve viral clearance, peginterferon alfa-2b has to be given at least twice weekly.

The study, conducted at the University of Vienna, investigated whether twice weekly dosing of PegIntron™ improves viral kinetics over once weekly dosing. Twenty interferon-naïve patients with chronic hepatitis C genotype 1 were randomised to receive either 1.0mcg/kg peginterferon alfa-2b once weekly (Group A, 10 patients) or twice weekly (Group B, 10 patients) for four weeks. Serum concentrations and viral load were measured. In Europe, the monotherapy dose for peginterferon alfa-2b is 0.5 or 1.0 mcg/kg/week, of which the 1.0 dose was used for this monotherapy study.

Key study findings:
· Serum concentrations of peginterferon alfa-2b reached maximum levels 24 hours after injection followed by a linear decline over the subsequent days. On the day before administration of the next dose, no drug was detectable in 90 per cent of patients in Group A (once weekly dosing). This same pattern was observed during the next three weeks of therapy.
· In contrast, in Group B with twice-weekly dosing, drug levels were detectable at any given time point and higher than in Group A.
· Viral load decreased in all patients within 2 days after the first dose of peginterferon alfa-2b but increased again on day 3. In Group A with once weekly dosing, viral load continued to increase throughout the week, and a similar pattern was observed in the second week. In contrast, in Group B with twice weekly dosing, viral load decreased again on day 4 and remained lower throughout the four-week study period.

· The authors noted that the viral load increases in parallel with the decrease of peginterferon alfa-2b, and this "clearly indicates that this rebound of HCV RNA is because of insufficient interferon levels in the body. This rebound may be predictive for nonresponse to peginterferon alfa-2b/ribavirin therapyi.(1)"

Previous studies have also shown that the once weekly administration of PegIntron™ does not result in the continuous decline in viral load

References:
1. Formann, E et al. Twice-weekly administration of peginterferon alfa-2b improves viral kinetics in patients with chronic hepatitis C genotype 1. J. Viral Hepatitis. 2003;10: 271-276.


SOURCE: Burson-Marsteller

Schering-Plough Corporation on 07/31/03 announced that the US Food and Drug Administration (FDA) has granted marketing approval to Rebetol (ribavirin, USP) Oral Solution and Capsules for use in the treatment of pediatric hepatitis C.  The company released the following announcement on the new indication for Rebetol:        

“Rebetol combination therapy with Intron A (interferon alfa-2b) represents the first and only therapy approved in the United States for treating hepatitis C in children,” said Robert J. Spiegel, M.D., senior vice president of medical affairs and chief medical officer, Schering-Plough Research Institute.  “For more than a decade, Schering-Plough has been the leader in developing new treatments for chronic hepatitis C.  We remain committed to developing innovative therapies to meet the needs of patients with hepatitis C and other serious diseases.”   

“In the pediatric population, REBETOL is indicated for use in combination with INTRON^Ò A (interferon alfa-2b, recombinant) Injection for the treatment of chronic hepatitis C in patients 3 years of age and older with compensated liver disease previously untreated with alpha interferon.  For these patients, individualized combination therapy is recommended, with REBETOL dosed according to patient body weight and INTRON A dosed according to patient size measured in body surface area.  The recommended duration of therapy is 24 weeks for pediatric patients with genotype 2/3 virus and 48 weeks for pediatric patients with genotype 1 virus.  

The New Drug Application (NDA) for REBETOL for pediatric use was submitted to FDA in January 2003 and received priority review.  Priority review status is granted to drugs that, if approved, would address unmet medical needs and represent significant advances over existing treatments.  It is estimated that less than 200,000 children in the United States are infected with the hepatitis C virus.  

“Schering-Plough also noted that FDA has granted orphan-drug designation to REBETOL for the treatment of chronic hepatitis C in pediatric patients.”   

“REBETOL Oral Solution represents a new formulation of ribavirin, USP.  REBETOL Capsules are approved in the United States for use in combination therapy with INTRON A for the treatment of chronic hepatitis C in patients with compensated liver disease previously untreated with alpha interferon or who have relapsed following alpha interferon therapy

”REBETOL Capsules also are indicated in combination with PEG-INTRON^Ò (peginterferon alfa-2b, recombinant) Injection for the treatment of chronic hepatitis C in patients with compensated liver disease who have not been previously treated with interferon and are at least 18 years of age.      

Commitment to Hepatitis C Patients

“Schering-Plough is committed to supporting hepatitis C patients with education and service programs as well as to help locate financial assistance for patients in need.  The company’s programs for patients in the United States are among the most comprehensive in the industry, providing support and guidance to patients, and ensuring that all eligible patients have access to the company’s hepatitis C products.”

“Since the introduction of PEG-INTRON and REBETOL combination therapy in 2001, more than 250,000 hepatitis C patients worldwide have received this treatment, including 150,000 patients in the United States.  Twenty-five percent of all U.S. patients currently treated with PEG-INTRON and REBETOL are enrolled in the company’s Commitment to Care program, which provides medication and/or reimbursement assistance to eligible patients.  The market value of assistance and treatment provided to hepatitis C patients through this program exceeded $100 million in 2002.” 

“Schering-Plough’s Be In Charge hepatitis C patient-support program has enrolled more than 55,000 U.S. patients to date, with more than 25,000 patients enrolling in 2002 alone.  This U.S. program is designed to support patients treated with Schering-Plough hepatitis C products through the use of educational materials and telephone contact with personal nurse counselors skilled in the management of hepatitis C.” 

WARNING

·         REBETOL monotherapy is not effective for the treatment of chronic hepatitis C virus infection and should not be used alone for this indication.  (See WARNINGS.)