Pegasys + ribavirin (Edie)
Here is one study, and although it is comprised of a very small group
of people, you have to admitt it is still pretty interesting! And no, this
isn't the study I was thinking was on relapsers, I believe these people had
never been treated.
Treatment of HCV with Long-Acting "Pegylated" Alfa * Interferon Shows
For 16 patients with genotype 1, end-of-treatment response rate is 63%;
4 patients with genotype 2, sustained response rate is 100%
by Harvey Bartnof, MD
There were several abstracts today that addressed the experimental
forms of alfa * interferon. Pegylated means that the active drug is
in a fat molecule called polyethylene glycol, or "peg" in an
acronym. This slows the metabolism significantly, allowing for a once
injection instead of the 3-times weekly approved dosing for the
non-pegylated form. The version from Hoffman-La Roche will be called
(pegylated interferon alfa-2a, while the version from Schering-Plough
be called Peg-Intron (pegylated interferon alfa-2b).
Hoffman-La Roche's Pegasys
A phase II, single arm, open-label study was presented that combined
Pegasys with Rebetol (ribavirin) for the treatment of chronic infection
hepatitis C virus (HCV). The lead author was M. Sulkowski, MD, from The
Johns Hopkins University School of Medicine. Even though there were
patients, the results were impressive. Sixteen of the patients had
1, which is the most difficult to treat. The other four patients had
genotype 2, which is more responsive to treatment. All 20 patients had
chronic hepatitis C. This was defined as (1) a persistently elevated
ALT (alanine aminotransferase, liver enzyme); (2) an HCV RNA viral load
greater than 2,000 copies per milliliter using the Amplicor Monitor
and (3) an abnormal liver biopsy sample consistent with "compensated
non-cirrhotic liver disease." All patients were therapy-naove (never
for hepatitis C). Exclusion criteria included heart disease, kidney
pre-existing severe depression or other psychiatric disorders, seizure
disorder, retinopathy (eye disease), other liver diseases, and HIV
The dosage was once-weekly Pegasys (180 micrograms) injection under the
plus oral Rebetol 1,000-1,200 mg daily. Since genotype 1 is more
to therapy, the duration of treatment for those patients was 48 weeks,
there was a normal ALT or undetectable HCV viral load at 24 weeks. For
with genotype 2, the treatment duration was 24 weeks. Those durations
reflect the standard guidelines based on genotype testing. The median
baseline HCV viral load was not stated.
The results showed that for those patients with genotype 1, the
end-of-treatment response was 63%. That means that 63% had an
HCV viral load (limit 100 copies per milliliter) at the end of 48 weeks
therapy. (All results are reported using a stricter "intent-to-treat"
analysis, meaning that all enrolled patients are included.) Whereas,
those patients with genotype 2, the sustained response rate was 100%.
with genotype 2 received 24 weeks of therapy, followed by a 24-week
treatment-free follow-up period.) While the numbers of patients are
these viral load undetectability rates are among the highest ever
for patients treated for hepatitis C.
When the results of the entire 20 patients were analyzed together, at
48-week time point, the following were found: the percentage with a
ALT was 60%, while those with an undetectable HCV viral load was 70%.
Interestingly, the percentage with an undetectable viral load at 12
was also approximately 70%.
Adverse events included lowered blood cell counts, which are known side
effects. The neutrophil (white blood cell) count and hemoglobin
(oxygen-carrying molecule in red blood cells, lowered in anemia)
at week four. The decrease in blood platelets (for normal clotting)
stabilized by week 12. No patient withdrew from the study due to
laboratory test results.
Two patients (10%) withdrew prematurely from the study. One had a
("convulsion" or "fit"), while another had bleeding in the back of the
(retinal hemorrhage). Interferon has been associated with a lowered
threshold in past studies. The hemorrhage was not depicted further in
poster presentation. However, eight patients did have dosing changes,
adverse events. Four changes were due to anemia and two were due to
neutropenia. Six other patients had a dose modification due to "other
The patients will be followed for a longer period. The poster did not
whether liver biopsies would be performed at the end of the observation
period. The evaluation of a liver biopsy correlates much better with
long-term disease progression. HCV viral loads do not necessarily
with long-term outcome.
Even though these results are only interim, the authors conclude that
combination of Pegasys and Rebetol "appears to have acceptable
and promising antiviral activity in the treatment of chronic hepatitis
It is quite possible that the sustained response rate for those with
genotype 1 will be lower than the end-of-treatment response (ETR) rate.
Often, this is the observed pattern. However, an ETR of 63% for
is higher than has been reported for any other therapy(ies) to date. It
appears that significant advances are being made in the treatment of
In a separate poster presentation, the half-life (amount of time for
an original amount to be remaining) of Pegasys was found to be 77
while a standard interferon injection had a half-life of nine hours.
phase II dose-ranging study had 20 HCV negative volunteers. The
the study evaluated pharmacokinetic and pharmacodynamic (metabolism
measurements) of Pegasys. The authors determined that the weekly
self-injected dose under the skin would be 180 micrograms. The lead
was N.E. Algranati, MD, from Hoffman-La Roche.
Schering Plough's PEG-Intron
Another poster addressed a different formulation of the same drug.
PEG-Intron (pegylated Intron, interferon alfa-2b, Schering-Plough)
under the skin once weekly showed the same or better anti-HCV effects
standard Intron-A dosed at 3 million units injected 3-times weekly. The
pharmacokinetics and pharmacodynamics (metabolism measurements) of this
acting form of the drug were measured in a 24-week study of HCV
patients. The half-life (time for an original amount to be reduced by
of PEG-Intron was calculated to be 54 hours, compared to 8 hours for
standard Intron-A. No unexpected adverse effects occurred. Common
include "flu"-like symptoms. Abnormal laboratory values included a low
cell count (neutropenia) and a low blood platelet count (for normal
clotting, thrombocytopenia). The weekly dose will be 0.5 micrograms per
kilogram once weekly (weight in pounds X 0.454 = weight in kilograms).
lead author was Paul Glue, MD, from Schering-Plough.
* Note that all generic versions use the spelling 'alfa' and not
Algranati NE and others. A branched methoxy 40 KD/ polyethylene glycol
moiety optimizes the pharmacokinetics (PK) of peg-interferon alpha-2a
(PEG-IFN) and may explain its enhanced efficacy in chronic hepatitis C
(CHC). Abstract and poster presentation 120 at the 50th Annual Meeting
the American Association for the Study of Liver Diseases. Dallas,
November 5-9, 1999. Hepatology 30(4) Supp2, 190A. Glue P and others.
Peg-interferon-alpha-2b: pharmacokinetics, pharmacodynamics, safety and
preliminary efficacy data. Abstract and poster presentation 115 at the
Annual Meeting of the American Association for the Study of Liver
Dallas, Texas; November 5-9, 1999. Hepatology 30(4) Supp2, 189A.
and others. Combination therapy with peginterferon alfa-2a (PEG-IFN)
ribavirin in the treatment of patients with chronic hepatitis C: a
open-label study. Abstract and poster presentation 145 at the 50th
Meeting of the American Association for the Study of Liver Diseases.
Texas; November 5-9, 1999. Hepatology 30(4) Supp2, 197A.
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