April 02, 2011 03:30 AM Eastern Daylight Time
Idera Pharmaceuticals Presents Data from a Phase 1 Clinical Trial of
IMO-2125 in Treatment-Naïve Genotype 1 HCV Patients at EASL 2011
- Phase 2 clinical trial expected to begin in second quarter 2011-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today the
presentation of data from a four-week Phase 1 clinical trial of IMO-2125
in combination with ribavirin in treatment-naïve patients chronically
infected with hepatitis C virus (HCV) genotype 1. During the four weeks
of treatment, IMO-2125 in combination with ribavirin was well tolerated
and produced clinically meaningful antiviral activity. IMO-2125 is a
Toll-like Receptor 9 (TLR9) agonist that stimulates production of
natural interferons and other antiviral cytokines. The presentation
(Abstract #1209), entitled “IMO-2125 plus ribavirin gives substantial
first-dose viral load reductions, cumulative antiviral effect, is well
tolerated in naïve genotype 1 HCV patients: a Phase 1 trial”, was made
at the 46th Annual Meeting of the European Association for
the Study of the Liver (EASL) being held in Berlin, Germany from March
30 – April 3, 2011. The presentation provided additional detail from the
trial for which interim data was announced in December 2010.
“This study provides several key results that support our IMO-2125
development program”
“This study provides several key results that support our IMO-2125
development program,” said Robert Arbeit, M.D., Vice President of
Clinical Development at Idera. “First, IMO-2125 in combination with
ribavirin had substantial antiviral activity in treatment-naïve
patients. This antiviral activity was associated with decreases in serum
liver enzyme levels over the four-week course of treatment. Second,
IMO-2125 was well tolerated, and demonstrated important safety features
in comparison to Pegasys® used in the control arm. These
included shorter duration of flu-like symptoms and minimal hematologic
toxicity, with no IMO-2125-treated patients developing neutropenia
requiring intervention or platelet levels below lower limits of normal.”
Dr. Arbeit continued, “We are preparing to initiate a 12-week Phase 2
clinical trial of IMO-2125 plus ribavirin in treatment-naïve genotype 1
HCV patients in the second quarter of 2011. We expect to use data from
that study to select dosages for subsequent clinical trials of IMO-2125
in combination with ribavirin and a direct acting antiviral agent.”
"We have now completed Phase 1 clinical evaluation of IMO-2125 in both
treatment-naïve and null-responder HCV patients and have established
that its immune stimulation mechanism of action provides clinically
meaningful antiviral activity and is well tolerated,” said Tim Sullivan,
Ph.D., Vice President of Development Programs and Alliance Management at
Idera. "By the end of this year we expect to have completed chronic
nonclinical safety studies to support further clinical development of
IMO-2125 as an immune modulatory component of HCV therapy.”
"Our objective is to develop a novel immune modulator for the treatment
of HCV as a potential alternative to pegylated interferons,” said Sudhir
Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We
have confirmed the intended mechanism of action of IMO-2125 and are very
pleased with its safety profile and antiviral activity in both
null-responder and treatment-naïve HCV patients. We look forward to
initiating the Phase 2 clinical trial, which we expect will provide the
additional data needed to advance the clinical development of IMO-2125
and support studies in combination with direct-acting antiviral agents.”
Phase 1 Clinical Trial in Treatment-naive HCV Patients
Study Design:
In this Phase 1 clinical trial, treatment-naïve genotype 1 HCV patients
received IMO-2125 by subcutaneous injection over four weeks in
combination with daily oral administration of standard, weight-based
doses of ribavirin in one of four treatment regimens of 12 patients
each. The four regimens of IMO-2125 were 0.08, 0.16, and 0.32 mg/kg once
weekly and 0.16 mg/kg twice weekly. In addition, 12 patients received
Pegasys® plus ribavirin. Study endpoints of safety and
antiviral activity were measured through Day 29. Upon completion of the
four weeks of protocol-specified treatment, all patients received
follow-on treatment with Pegasys® plus ribavirin. Under the
trial protocol, final safety and antiviral assessments were taken at Day
59, four weeks after the follow-on treatment with Pegasys®
plus ribavirin was initiated.
Study Results:
Patient Population
All patients were Caucasian, except one Asian patient in the 0.16
mg/kg/week IMO-2125 group; all were infected with HCV genotype 1.
Additional demographic and baseline data are summarized in the following
table.
IMO-2125 was well tolerated at all dose levels in combination with
ribavirin over four weeks of treatment, with no treatment-related
serious adverse events and no treatment discontinuations. The most
common adverse events observed in the IMO-2125 regimens were mild to
moderate flu-like symptoms and injection site reactions.
Flu-like symptoms. Among patients who received IMO-2125,
flu-like symptoms consisted primarily of fever and chills with onset
within approximately eight hours of dosing and of brief duration,
typically lasting less than one day. In contrast, the observations for
the patients receiving Pegasys® who experienced flu-like
symptoms were consistent with the extensively published experiences
showing that flu-like symptoms generally include malaise and fatigue,
have delayed onset at one or two days after dosing, and often last two
days or more.
Neutropenia. Neutropenia (absolute neutrophil count (ANC)
<1000/mm3) with IMO-2125 plus ribavirin treatment was
infrequent, occurring in five of 48 patients, or 10%, at some point
during the four-week treatment period. Neutropenia in patients treated
with IMO-2125 plus ribavirin was transient; no patients required
intervention and at Day 29 no patients had ANC <1000/mm3.
Neutropenia was more common with Pegasys® plus ribavirin
treatment, occurring in seven of 12 patients, or 58%. Two of these
patients, or 17%, required intervention for their neutropenia and at
Day 29 two additional patients had ANC <1000/mm3.
At Day 29, all 48 patients who had received IMO-2125 initiated standard
of care treatment with Pegasys® plus ribavirin. At Day 59,
six of these patients, or 13%, had neutrophil counts less than 1000/mm3.
of care treatment with Pegasys® plus ribavirin. At Day 59,
six of these patients, or 13%, had neutrophil counts less than 1000/mm3.
Thrombocytopenia. On Day 29, all patients treated with IMO-2125
plus ribavirin had platelet counts of 145,000/mm3 or
greater. Three of the 12 patients, or 25%, treated with Pegasys®
plus ribavirin had platelet counts at or below 130,000/mm3
on Day 29.
At Day 29, all 48 patients who had received IMO-2125 initiated standard
of care treatment with Pegasys® plus ribavirin. At Day 59, 13
of these patients, or 26%, had platelet counts at or below 130,000/mm3.
Liver Enzyme Normalizationof care treatment with Pegasys® plus ribavirin. At Day 59, 13
of these patients, or 26%, had platelet counts at or below 130,000/mm3.
Serum liver enzyme levels, AST and ALT, are generally elevated in
chronic hepatitis C patients. Treatment with all dose levels of
IMO-2125 plus ribavirin led to progressive reductions in group means
of AST and ALT to within normal limits by the end of the fourth week
of treatment. Similar reductions in AST and ALT levels were observed
in patients receiving treatment with Pegasys® plus
ribavirin.
Viral load reduction after first dose. IMO-2125
at all dose levels induced declines in viral levels at 48 hours after
the first dose. The mean viral load reductions at 48 hours after the
first dose with the 0.16 mg/kg once-weekly, 0.32 mg/kg once-weekly and
0.16 mg/kg twice-weekly IMO-2125 regimens were -2.5, -1.3, and -1.6 log10,
respectively. The mean viral load reduction for patients treated with
Pegasys® plus ribavirin at the same time point was -1.4 log10.
Viral load reduction after four weeks. Antiviral
response was variable within all treatment groups, including Pegasys®
plus ribavirin. At Day 29, in each of the IMO-2125 treatment groups at
0.16 mg/kg/week or higher and in the Pegasys® plus
ribavirin group, some patients achieved greater than 4 log10
reductions in viral load and some failed to achieve even a 1 log10
reduction.
Mean viral load reductions from baseline at the mid-week evaluation in
the fourth week of treatment with the 0.16 mg/kg once-weekly, 0.32 mg/kg
once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -3.4,
-2.0, and -3.3 log10, respectively. The mean viral load
reduction for patients treated with Pegasys® plus ribavirin at the same
timepoint was -3.8 log10.
the fourth week of treatment with the 0.16 mg/kg once-weekly, 0.32 mg/kg
once-weekly and 0.16 mg/kg twice-weekly IMO-2125 regimens were -3.4,
-2.0, and -3.3 log10, respectively. The mean viral load
reduction for patients treated with Pegasys® plus ribavirin at the same
timepoint was -3.8 log10.
Mean viral load reductions from baseline at Day 29 with the 0.16 mg/kg
once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125
regimens were -1.7, -0.6, and -2.4 log10, respectively. The
mean viral load reduction for patients treated with Pegasys®
plus ribavirin at Day 29 was -3.4 log10.
once-weekly, 0.32 mg/kg once-weekly and 0.16 mg/kg twice-weekly IMO-2125
regimens were -1.7, -0.6, and -2.4 log10, respectively. The
mean viral load reduction for patients treated with Pegasys®
plus ribavirin at Day 29 was -3.4 log10.
Prognostic factors affecting antiviral activity. Uneven
distribution of negative prognostic factors, such as IL28B CT or TT
genotype, high baseline IP-10, and age, contributed to the variability
in antiviral activity across the treatment groups. Additional data on
IL28B genotype are being collected.
Guyader, M.D., of Universite de Rennes, France, Pavel Bogomolov, M.D.,
of the State Institution Moscow Region named after M.F. Vladymirsky,
Moscow, Russia, Zhanna Kobalava, M.D., of GOUVPO Russian Peoples’
Friendship University (City Clinical Hospital #64), Moscow, Russia,
Valentin Moiseev, M.D., of GOUVPO Russian Peoples’ Friendship University
(City Clinical Hospital #3), Moscow, Russia, Janos Szlavik, M.D., of Szt
László Hospital, Budapest, Hungary, Béatrice Astruc, M.D., of Biotrial,
Rennes, France, Istan Varkonyi, M.D., of Kenezy Hospital, Debrecen,
Hungary, Tim Sullivan, Ph.D., Kerry Horgan, Alice Bexon, MBChB, and
Robert Arbeit, M.D., of Idera Pharmaceuticals.
About IMO-2125
IMO-2125, a Toll-like
Receptor (TLR) 9 agonist,
is a novel immune modulator being developed as a component of treatment
for chronic hepatitis C virus (HCV) infection. IMO-2125 is designed to
stimulate the immune system, causing the body to generate natural
interferons and other antiviral cytokines. IMO-2125 has been evaluated
in a Phase 1 clinical trial in null-responder HCV patients as
monotherapy for 4 weeks and in a Phase 1 clinical trial in
treatment-naïve HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat chronic
hepatitis C virus infection, autoimmune and inflammatory diseases,
cancer, and respiratory diseases, and for use as vaccine adjuvants. The
company's proprietary drug candidates are designed to modulate specific
Toll-like Receptors, which are a family of immune system receptors.
Idera's pioneering DNA and RNA chemistry expertise enables us to create
drug candidates for internal development and generates opportunities for
multiple collaborative alliances. For more information, visit http://www.iderapharma.com/.
Idera Forward Looking Statements
This press release contains forward-looking statements concerning Idera
Pharmaceuticals, Inc. that involve a number of risks and uncertainties.
For this purpose, any statements contained herein that are not
statements of historical fact may be deemed to be forward-looking
statements. Without limiting the foregoing, the words "believes,"
"anticipates," "plans," "expects," "estimates," "intends," "should,"
"could," "will," "may," and similar expressions are intended to identify
forward-looking statements. There are a number of important factors that
could cause Idera's actual results to differ materially from those
indicated by such forward-looking statements, including whether results
obtained in preclinical studies and early clinical trials such as the
studies and trials referred to in this release will be indicative of
results obtained in future clinical trials; whether products based on
Idera's technology will advance into or through the clinical trial
process on a timely basis or at all and receive approval from the United
States Food and Drug Administration or equivalent foreign regulatory
agencies; whether, if the Company's products receive approval, they will
be successfully distributed and marketed; whether the Company's
collaborations will be successful; whether the patents and patent
applications owned or licensed by the Company will protect the Company’s
technology and prevent others from infringing it; whether Idera's cash
resources will be sufficient to fund the Company's operations; and such
other important factors as are set forth under the caption "Risk
Factors" in Idera's Annual Report on Form 10-K for the year ended
December 31, 2010 which important factors are incorporated herein by
reference. Idera disclaims any intention or obligation to update any
forward-looking statements.
Pegasys® is a registered trademark of F. Hoffmann-La Roche
Company.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
E-mail: tdahlman@iderapharma.com
or
MacDougall
Biomedical Communications
Chris Erdman, 781-235-3060
E-mail: cerdman@macbiocom.com
Teri Dahlman, 617-679-5519
E-mail: tdahlman@iderapharma.com
or
MacDougall
Biomedical Communications
Chris Erdman, 781-235-3060
E-mail: cerdman@macbiocom.com
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