Squibb and ZymoGenetics Present
Final Phase 1b Results for PEG-Interferon Lambda in
activity seen at all dose levels tested
support moving to dose-ranging Phase II studies in
treatment-naive HCV patients
NJ and Seattle, WA -- October 31, 2009 -- Bristol-Myers
Squibb Company (NYSE: BMY) and ZymoGenetics, Inc.
(NASDAQ: ZGEN) today presented final results from
a Phase 1b clinical trial of PEG-Interferon lambda
administered with ribavirin in relapsed and treatment-naive
hepatitis C virus (HCV) patients.
poster included data on 56 patients in the study.
Antiviral activity was observed at all dose levels
tested. The results will be presented at the American
Association for the Study of the Liver Diseases annual
meeting in Boston on November 3. Interim results were
previously presented at the European Association for
the Study of the Liver annual meeting in April 2009.
is a strong need for additional options for hepatitis
C patients," said Brian Daniels, MD, senior vice
president, Global Development & Medical Affairs,
Bristol-Myers Squibb. "We are pursuing this investigational
pathway to address the fact that although current
interferons have been the backbone of therapy with
meaningful efficacy, they are often poorly tolerated,
leading to dose reductions, poor compliance and avoidance
are excited about the prospects for PEG-Interferon
lambda as a potential HCV treatment," said Eleanor
L. Ramos, MD, senior vice president and chief medical
officer of ZymoGenetics. "There is a clear unmet
medical need for an interferon with improved safety
and tolerability. We look forward to obtaining additional
clinical data on this promising investigational medicine."
Phase 1b clinical trial was designed to evaluate the
safety and antiviral activity of PEG-Interferon lambda
when given as a single agent or in combination with
ribavirin in genotype 1 HCV patients with relapsed
disease and in treatment-naive patients.
the single agent arm of the study with treatment-relapsed
patients (n=24), PEG-Interferon lambda was administered
subcutaneously at 1.5 mcg/kg and 3.00 mcg/kg weekly
for four weeks, and 1.5 mcg/kg and 3.00 mcg/kg every
two weeks. In the combination arm of the study with
treatment-relapsed patients (n=24), PEG-Interferon
lambda was administered subcutaneously weekly at 0.5
mcg/kg, 0.75 mcg/kg, 1.5 mcg/kg and 2.25 mcg/kg for
four weeks, with daily oral ribavirin administered
consistent with the package insert. Patients in the
cohort of treatment-naive patients (n=7) were given
1.5 mcg/kg of PEG-Interferon lambda and ribavirin.
lambda demonstrated antiviral activity at all dose
levels tested in both relapse and treatment naive
HCV patients. A majority of patients across all treatment
arms achieved a greater than 2 log reduction in HCV
the patients in the single agent arm of the study,
all 12 of those patients receiving 1.5 mcg/kg and
3.0 mcg/kg weekly for four weeks achieved a greater
than 2 log decrease in HCV RNA. Five of the 12 patients
receiving 1.5 mcg/kg and 3.00 mcg/kg every two weeks
for four weeks achieved a greater than 2 log decrease
in HCV RNA.
PEG-Interferon lambda doses of 0.75 mcg/kg, 1.5 mcg/kg
and 2.25 mcg/kg administered in combination with ribavirin
in treatment-relapsed patients (n=18), a greater than
3 log mean maximum decrease in viral load was observed.
Of those patients, eleven (61%) had less than 1,000
HCV RNA copies at Day 29.
patients, who were treated with 1.5 mcg/kg of PEG-Interferon
lambda in combination with ribavirin (n=7), also had
a greater than 3 log mean maximum decrease in viral
load and two patients (29%) achieved a rapid virologic
response (RVR), or undetectable HCV RNA copies, at
most common adverse events were fatigue (29%) and
nausea (13%). There were minimal effects on neutrophil
counts. Minimal constitutional symptoms or hematologic
effects were observed with PEG-Interferon lambda given
as a single agent or in combination with ribavirin.
The majority of adverse events and laboratory changes
were grade 1 or 2. Dose-limiting elevations in ALT
or AST, with or without an increase in bilirubin,
were dose-dependent and reversible.
the results of the study support moving to dose-ranging
Phase 2 studies in treatment-naive HCV patients.
lambda (IL-29) is a type 3 interferon that binds
to a unique receptor with more restricted distribution
than the receptors targeted by type 1 interferons,
such as interferon alpha. It is in development for
hepatitis C. The native human protein Interferon
lambda is generated by the immune system in response
to viral infection. IL-29 is a member of the type
3 Interferon family, which includes IL-28A and IL-28B,
and signals through the same receptor as IL-28A
Squibb is a global biopharmaceutical company committed
to discovering, developing and delivering innovative
medicines that help patients prevail over serious
diseases. For more information, please visit www.bms.com.
is focused on the creation of novel protein drugs
to improve patient care and address unmet medical
needs. The company's strategy is to discover, develop
and commercialize its products independently, in
collaboration with partner companies or through
out-licensing. ZymoGenetics developed and markets
Recothrom Thrombin, topical (Recombinant), a synthetic
version of a human blood-clotting enzyme used to
stop bleeding during surgery. The company is developing
a proprietary portfolio of immune-based product
candidates. PEG-Interferon lambda is a novel type-3
interferon in clinical development for the treatment
of chronic hepatitis C infection. Interleukin-21
is a novel cytokine in clinical development for
the treatment of metastatic melanoma and renal cell
carcinoma. Several other proprietary product candidates
are in preclinical development. In addition, ZymoGenetics
has licensed rights to multiple clinical and preclinical
drug candidates being developed by other companies.
For further information, visit www.zymogenetics.com.