Both available forms of pegylated
interferon alfa (Pegasys
and PegIntron)
are injected once weekly -- which is a considerable improvement over conventional
interferon, which was administered 3 times per week. For some patients, less frequent
injection is associated with fewer side effects and improved quality of life.
Human
Genome Sciences and Novartis are collaborating on the development of an even longer-acting
form of interferon alfa -- albumin interferon (Albuferon) -- which can be injected
once every 2 weeks. Data from studies of albumin interferon were presented at
the 42nd Annual Meeting of the European Association for
the Study of the Liver last month in Barcelona, Spain.
Genotype 1 Patients
In a late-breaker session, Stefan
Zeuzem, MD, presented data from an ongoing Phase IIb study evaluating the safety
and efficacy of albumin interferon in treatment-naive genotype 1 chronic hepatitis
C patients. A total of 458 subjects in 8 countries were randomly assigned to receive
1 of 3 doses of subcutaneous albumin interferon -- 900 or 1200 mcg once every
2 weeks (Q2W) or 1200 mcg once every 4 weeks (Q4W) – or else 180 mcg once-weekly
Pegasys for 48 weeks; all patients also received ribavirin.
Interferon
efficacy is usually assessed based on sustained virological response (SVR), or
undetectable HCV RNA 24 weeks after the completion of therapy. Here, the researchers reported interim
“SVR12” results 12 weeks after the end of therapy; follow-up is continuing.
Results
By
intention-to-treat analysis, SVR12 rates in the various arms were as follows:
o
Albumin interferon Q2W 900 mcg: 59.3%; o Albumin interferon Q2W 1200 mcg: 55.5%; o
Albumin interferon Q4W 1200 mcg: 52.6%; o Pegylated interferon: 54.4%.
Among
subjects who achieved at least 80% adherence to prescribe interferon and ribavirin
doses, SVR12 rates were higher across all arms, but the improvement was most pronounced
in the Q2W albumin interferon arms:
o
Albumin interferon Q2W 900 mcg: 73.8%; o Albumin interferon Q2W 1200 mcg: 72.0%; o
Albumin interferon Q4W 1200 mcg: 67.5%; o Pegylated interferon: 63.0%.
Among heavier patients (75 kg or more, a group that responds
more poorly to therapy) with optimal adherence, SVR12 rates were maintained in
the albumin interferon arms, but lower in the pegylated interferon arm:
o
Albumin interferon Q2W 900 mcg: 80.6%; o Albumin interferon Q2W 1200 mcg: 70.4%; o
Albumin interferon Q4W 1200 mcg: 66.7%; o Pegylated interferon: 56.7%.
Among adherent patients, relapse rates were reduced in
all albumin interferon arms, especially Q2W 900 mcg (13.0%), compared with pegylated
interferon (29.7%).
Rates of premature discontinuation due to adverse events
in the 4 arms were as follows:
o
Albumin interferon Q2W 900 mcg: 9.3%; o Albumin interferon Q2W 1200 mcg: 19.1%; o
Albumin interferon Q4W 1200 mcg: 12.1%; o Pegylated interferon: 6.1%.
Quality of life as measured by the SF-36 scale was most
favorable in the albumin interferon Q2W 900 mcg arm.
Conclusion
The researchers concluded that, “These data
suggest that the Q2W albumin interferon regimens may offer at least comparable or increased efficacy, with an improved
dosing schedule and the potential for less impairment in quality of life compared with Q1W pegylated interferon. The Q4W 1200
results warrant further investigation of Q4W dosing in clinical trials.”
J.W.
Goethe-University Hospital, Germany; Hopital Pitie-Salpetriere, France; University
of Alberta, Canada; Hadassah University, Israel; Monash University, Australia;
Medical University of Bialystok, Poland; Spitalul Clinic de Adulti Cluj-Napoca,
Romania; Nuselská poliklinika – Remedis, Czech Republic; University of British
Columbia, Canada; University Of Manitoba, Canada; Duke Clinical Research Institute,
Durham, NC; Human Genome Sciences, Rockville, MD.
Genotype
2 or 3 Patient
In
a second study, V.G. Bain and colleagues assessed albumin interferon in treatment-naive
patients with genotype 2 or 3 HCV. In this multicenter, open-label Phase II trial,
43 subjects were randomly assigned to receive subcutaneous albumin interferon
at a dose of 1500 mcg either Q2W or Q4W plus 800 mg/day ribavirin. Patients were
treated for 24 weeks, the standard duration of pegylated interferon therapy for
these genotypes.
Rapid
virological response rates at week 4 were 76% in the Q2W arm and 68% in the Q4W
arm; after 24 weeks, however, the end-of-treatment response rates were 71% and
82%, respectively. Albumin interferon was well tolerated overall, with similar
safety profiles in the 2 dose groups. There were no dose reductions in the Q4W
arm compared with 10% in the Q2W. SVR
data from this study are pending.
University
of Alberta, Edmonton, Canada; University of Western Ontario, London, ON, Canada;
University of Manitoba, Winnipeg, MB, Canada; University of British Columbia,
Vancouver, BC, Canada; University of Calgary, Calgary, AB, Canada; Bar Ilan University,
Ramat-Gan, Israel; Duke Clinical Research Institute, Durham, NC; Human Genome
Sciences, Inc., Rockville, MD.
05/04/07
References
S Zeuzem, Y Benhamou, VG Bain, and others. Antiviral response at week
12 following competion of treatment
with albinterferon alfa-2b plus ribavirin in genotype 1, IFN-naive, chronic hepatitis
C patients. 42nd Annual Meeting of the European Association for the Study of the
Liver (42nd EASL). Barcelona,
Spain. April 11-15,
2007.
VG
Bain, P Marotta, K Kaita. Comparable antiviral response rates with albumin interferon
alfa-2b dosed at Q2W or Q4W intervals in naive subjects with genotype 2 or 3 chronic
hepatitis C. 42nd EASL.
Index
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