Release Interferon (Locteron) Every 2 Weeks Works as Well as
Pegylated Interferon but with Fewer Side Effects
A controlled-release formulation of interferon alfa-2b
(Locteron), in combination with ribavirin, produced
hepatitis C virus (HCV) suppression similar to that
of pegylated interferon plus ribavirin over 12 weeks,
according to 3 studies presented at the 45th Annual
Meeting of the European Association for the Study
of the Liver (EASL 2010)
last month in Vienna. While similar proportions of
patients achieved undetectable HCV viral load, those
taking Locteron reported fewer flu-like side effects.
part of standard therapy for chronic
hepatitis C, pegylated interferon is administered once weekly
along with daily ribavirin. Locteron, which is being developed
by Biolex under a license from OctoPlus, is a microsphere-based
controlled-release recombinant formulation of interferon alfa-2b
that lasts longer in the body and can be taken once every 2
research has shown that Locteron's trough concentration
(lowest level) between doses maintained adequate antiviral activity.
In the open-label Phase 2b 480 Study, presented as an oral late-breaker
at EASL, Z. Krastev and colleagues enrolled 74 treatment-naive
chronic hepatitis C patients with compensated liver disease:
A: 42 patients in Romania and Bulgaria (6-week data; 12
weeks not yet analyzed);
B: 32 patients in Israel (12-week data).
were randomly assigned to receive 480 mcg Locteron once every
2 weeks or 1.5 mcg/kg pegylated
interferon alfa-2b (PegIntron) once weekly, both in combination
with weight-adjusted ribavirin, for 12 weeks.
data from Panel A showed that HCV viral load declined faster
in the Loceteron arm compared with the pegylated interferon
arm, with mean reductions of about 4 and 2 log, respectively,
and about 40% and 5%, respectively, achieving undetectable
12 weeks, according to data from Panel B, Locetron was non-inferior
to pegylated interferon, with average viral load reductions
of about 4 log and about 60% with undetectable HCV RNA in
of serious adverse events were similar in both arms for
both patient panels.
Panel A, participants receiving Locteron reported about
one third as many cumulative flu-like symptoms (headache,
chills, fever, muscle or joint pain) than pegylated interferon
recipients, but numbers were similar in the 2 arms of Panel
(blood) abnormalities including neutropenia (low neutrophil
count) occurred infrequently in both arms and were generally
the overall frequency of injection site reactions was similar,
Locteron recipients in Panel A were more likely than pegylated
interferon recipients to report indurations (hard swelling).
Lawitz and colleagues presented a poster describing findings
from the Phase 2b SELECT-2 trial, in which 116 treatment-naive
genotype 1 chronic hepatitis C patients from the U.S. and Europe
were randomly assigned to received once-weekly pegylated interferon
or Locteron every 2 weeks at doses of 320 mcg, 480 mcg, or 640
mcg, all with weight-based ribavirin, for 48 weeks. The researchers
monitored changes in HCV RNA and flu-like symptoms, based on
patient self-reports using an Internet interface.
36 weeks of treatment, mean HCV RNA decreases were similar
in the 640 mcg and 480 mcg Locteron arms and in the pegylated
receiving the 320 mcg Locteron dose eventually achieved
a similar decrease, but viral decline was slower at earlier
week 12, rates of undetectable HCV RNA in the 640 mcg, 480
mcg, and 320 mcg Locteron arms and the pegylated interferon
arm were 41%, 38%, 39%, and 40%, respectively (not a significant
rates were also similar at week 36, at 52%, 41%, 46%, and
36 weeks, participants in all 3 Locteron arms reported 65%
fewer flu-like symptoms compared with those in the pegylated
adverse events were uncommon in all arms.
taking 480 mcg or 640 mcg Locteron reported higher rates
of mild-to-moderate white blood cell and platelet loss,
but this did not lead to more treatment discontinuations.
W. Long from Biolex and colleagues presented another poster
describing findings from the EMPOWER study, which included 133
participants total from the 480 Study and the 480 mcg dose arm
of SELECT-2. This provided a large enough group to test the
hypothesis that Locteron would cause fewer flu-like symptoms
than pegylated interferon; the analysis had 85% power to detect
a 50% reduction in such symptoms.
HCV RNA decreased somewhat more rapidly with Locteron, but
comparable percentages achieved undetectable viral load
by week 12.
recipients reported approximately half as many flu-like
symptoms as those taking pegylated interferon.
recipients also reported missing fewer days of work.
recipients again experienced higher rates of mild-to-moderate
white blood cell and platelet loss, while pegylated interferon
recipients were more likely to experience mild-to-moderate
anemia; however, no severe hematological side effects were
observed with either drug.
study: Clinic of Gastroenterology, UMHAT St. Ivan Rilski, Sofia,
Bulgaria; UMHAT St. Marina, Varna, Bulgaria; UMHAT Alexandrovska,
Sofia, Bulgaria; Biolex Therapeutics, Pittsboro, NC; Medical
Institute Ministry of Interior, UMHAT Queen Giovanna - ISUL
EAD, Sofia, Bulgaria; Institute of Infectious Diseases, Prof.
Dr. Matei Bals, Bucharest, Romania; Infectious Diseases, Victor
Babes Clinical Hospital Craiova, Craiova, Romania; Internal
Medicine, Nephrology Center, Fundeni Clinical Institute, Bucharest,
Long study: Biolex Therapeutics, Pittsboro, NC; Military Medical
Academy, UMHAT Alexandrovska, Sofia, Bulgaria; UMHAT St. Marina,
Varna, Bulgaria; UMHAT St. Ivan Rilski, Bulgaria; UMHAT Queen
Giovanna - ISUL EAD, Bulgaria; Tokuda Hospital, Sofia, Bulgaria;
Alamo Medical Research, San Antonio, TX; Inova Health Systems,
Falls Church, VA; The Liver Institute at Methodist Dallas, Dallas,
TX; Carmel Medical Center, Haifa, Israel; Holy Family Hospital
Nazareth, Israel; Rabin Medical Center, Petah-Tikva, Israel;
Rebekah Ziv Medical Center, Zefat, Israel; Sourasky Medical
Center, Tel Aviv, Israel.
Lawitz study: Alamo Medical Research, San Antonio, TX; Inova
Health Systems, Falls Church, VA; Study Site, Chula Vista, CA;
Biolex Therapeutics, Pittsboro, NC; UMHAT St. Ivan Rilski, Bulgaria;
UMHAT Alexandrovska; Sofia, Bulgaria; Military Medical Academy,
Z Krastev, I Kotzev, K Tchernev, and others. Randomized, open-label,
12-week comparison of controlled-release interferon alpha2b
+ ribavirin vs pegylated-interferon alpha2b + ribavirin in treatment-naive
genotype 1 hepatitis C: 4 week results from 480 Study (Panel
A). 45th Annual Meeting of the European Association for the
Study of the Liver (EASL 2010). Vienna, Austria. April 14-18,
WA Long, D Takov, K Tchernev, and others. Q2week controlled-release-interferon-alpha2b
+ ribavrin reduces flu-like symptoms >50% and provides equivalent
efficacy in comparison to weekly pegylated-interferon-alpha2b
+ ribavirin in treatment-naive-genotype-1-chronic-hepatitis-C:
results from EMPOWER, a randomized-open-label-12-week-comparison
in 133 patients. 45th Annual Meeting of the European Association
for the Study of the Liver (EASL 2010). Vienna, Austria. April
14-18, 2010. (Abstract).
E Lawitz, Z Younoss, P Mehra, and others. Early viral response
of controlled-release interferon alpha2b and ribavirin vs. pegylated-interferon
alpha2b and ribavirin in treatment-naive genotype1 hepatitis
C: 12 week results (SELECT-2 trial). 45th Annual Meeting of
the European Association for the Study of the Liver (EASL 2010).
Vienna, Austria. April 14-18, 2010. (Abstract).
Biolex Announces Presentation at EASL of Interim Results from
SELECT-2 Phase 2b trial of Locteron in Chronic Hepatitis C.
Press release. April 15, 2010.
Announces Presentation at EASL of Interim Results from EMPOWER
Phase 2b trial of Locteron in Chronic Hepatitis C. Press release.
April 16, 2010.
N.V. OctoPlus Announces Publication of Positive Locteron Interim
Phase IIb Data. Press release. March 16, 2010.