April 02, 2011 03:30 AM Eastern Daylight Time
- 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,” 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.
Safety
• 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.
• 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 Normalization
• 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.
Effect on HCV RNA Viral Load
• 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.
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.
• 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.
See Table 2
Authors of the presentation and study investigators include Dominique 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
Source
Showing posts with label IMO-2125. Show all posts
Showing posts with label IMO-2125. Show all posts
April 4, 2011
March 8, 2011
Idera Pharmaceuticals Announces IMO-2125 Data Presentation at the 46th Annual Meeting of the European Association for the Study of the Liver
March 08, 2011 08:00 AM Eastern Time
2011 Meeting of the European Association for the Study of the Liver
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced that data from its Phase 1 clinical trial of IMO-2125, its novel immune modulator for the treatment of chronic hepatitis C virus (HCV) infection, in treatment-naïve genotype 1 HCV patients will be presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held March 30 – April 3, 2011 in Berlin, Germany. The presentation 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,” D. Guyader, et al., will be made in a poster session entitled Viral Hepatitis C: Clinical (new compounds, resistance) on Saturday, April 2, 2011. The full abstract (#1209) can now be accessed through the EASL website http://www.easl.eu/.
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, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, 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 it 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; whether results obtained in preclinical and clinical studies such as the studies 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 Quarterly Report on Form 10-Q for the three months ended September 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
2011 Meeting of the European Association for the Study of the Liver
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) today announced that data from its Phase 1 clinical trial of IMO-2125, its novel immune modulator for the treatment of chronic hepatitis C virus (HCV) infection, in treatment-naïve genotype 1 HCV patients will be presented at the 46th Annual Meeting of the European Association for the Study of the Liver (EASL) being held March 30 – April 3, 2011 in Berlin, Germany. The presentation 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,” D. Guyader, et al., will be made in a poster session entitled Viral Hepatitis C: Clinical (new compounds, resistance) on Saturday, April 2, 2011. The full abstract (#1209) can now be accessed through the EASL website http://www.easl.eu/.
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, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, 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 it 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; whether results obtained in preclinical and clinical studies such as the studies 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 Quarterly Report on Form 10-Q for the three months ended September 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
Contacts
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
December 21, 2010
Idera Pharmaceuticals Announces Preliminary Data from Phase 1 Clinical Trial of IMO-2125 in Treatment-Naïve Genotype 1 HCV Patients
-Outlines Phase 2 Clinical Development Plan-
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today preliminary data from a 4-week dose-ranging Phase 1 clinical trial of IMO-2125 in combination with ribavirin in 60 treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection. In the trial, treatment with IMO-2125 in combination with ribavirin was well tolerated and achieved substantial decline in virus levels at two days after the first dose of IMO-2125 and after four weeks of treatment. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist which stimulates production of natural interferons and other antiviral cytokines
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. "We believe that IMO-2125 may provide an alternative immune modulatory component to pegylated interferons in the anticipated HCV therapy combinations using direct-acting antivirals. In this treatment scenario, effective stimulation of the host immune system through TLR activation could minimize the risk of viral breakthrough.”
"Based on the overall data from this trial and our Phase 1 clinical trial of IMO-2125 in null-responder HCV patients, our next step in clinical development will be a 12-week Phase 2 trial of IMO-2125 in combination with ribavirin in treatment-naïve HCV patients,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We expect that the objectives of the Phase 2 study will be to determine optimal dosing, provide longer-term safety data and generate additional antiviral activity data in support of the future clinical development of IMO-2125.”
IMO-2125 Phase 1 Clinical Trial in Treatment-naïve Genotype 1 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 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 current standard of care treatment (Pegasys® plus ribavirin).
Study Results:
Safety
• Treatment with IMO-2125 in combination with ribavirin was well tolerated at all dose levels for 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 flu-like symptoms and injection site reactions.
• Of the 12 patients receiving the standard of care therapy in this trial, neutropenia requiring intervention occurred in two patients and platelet counts dropped below the normal range during the treatment period in seven patients. None of the 48 patients receiving IMO-2125 had neutropenia requiring intervention, and four of the 48 IMO-2125 patients had platelet counts drop below the normal range during the treatment period.
Antiviral Activity
• IMO-2125 induced substantial declines in viral levels at two days after the first dose at all dose levels.
• At the mid-week evaluation in the fourth week of treatment, mean viral load reductions with the three higher-dose IMO-2125 regimens ranged from -2.0 to -3.4 log10. Patients who received Pegasys® plus ribavirin achieved a mean viral load reduction of -3.8 log10 at the same timepoint.
• At the end of the fourth week of treatment, mean viral load reductions with the three higher-dose IMO-2125 regimens ranged from -0.6 to -2.4 log10. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the end of the fourth week of treatment was -3.4 log10.
• The initial dose level in this Phase 1 safety trial, 0.08 mg/kg/week, produced minimal changes in viral load although liver enzyme decreases were observed.
• Liver enzymes (AST/ALT) decreased during the treatment period and were within the normal range by the end of the fourth week of treatment in the majority of IMO-2125-treated patients.
• There was unequal distribution among the treatment groups of patients with poor prognostic factors at baseline, including CT or TT IL28B genotype, IP-10 values >600 pg/mL, and older age.
The Company plans to present detailed results of this study at a scientific meeting in 2011.
Planned Phase 2 Clinical Trial
In the planned 12-week Phase 2 randomized clinical trial, patients will be stratified for IL28B genotype (CC vs. CT/TT) and will receive either IMO-2125 plus ribavirin or Pegasys® plus ribavirin. The Company plans for recruitment of this clinical trial to start in the first quarter of 2011, pending regulatory concurrence. The Company expects that the objective of this clinical trial will be to provide the basis for subsequent clinical development of IMO-2125 as an alternative to pegylated-interferon in triple combination therapy with ribavirin and a direct-acting antiviral.
IMO-2125 Monotherapy Phase 1 Clinical Trial in Null-Responder HCV Patients
IMO-2125 has also been evaluated in a Phase 1 clinical trial in 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at one of five dose levels and 10 patients received placebo once per week for four weeks. Interim safety, antiviral activity and mechanism of action data were presented for the once-weekly dosing regimens in April 2010 at the Annual Meeting of the European Association for the Study of the Liver and complete data were presented in October 2010 at the Annual Meeting of the American Association for the Study of Liver Diseases.
Seven patients were enrolled in an additional cohort to evaluate twice-weekly dosing of IMO-2125 at 0.16 mg/kg/dose. Consistent with the patients’ null-responder status, 6 of 7 patients had CT or TT IL28B genotype. There were no treatment-related serious adverse events or discontinuations. As previously observed, the most common adverse events were injection site reactions and flu-like symptoms. Three patients in this cohort achieved greater than 1 log10 reduction, ranging from -1.9 to -3.5 log10, in viral load at least once during the treatment period. One of the patients with CT genotype achieved HCV viral levels at the lower limit of quantification (100 copies/mL) at Day 29, four days after the last IMO-2125 dose.
“We are pleased that the results of our Phase 1 clinical trials have shown that IMO-2125 stimulates the immune system in a manner consistent with the intended TLR9 agonist mechanism of action, and that this biological activity has led to reductions in HCV viral load,” said Tim Sullivan, Vice President of Development Programs and Alliance Management at Idera. “IMO-2125 was designed using our chemistry-based approach to optimize the activity of TLR-targeted drug candidates.”
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, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, 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 is developing drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs). TLRs, a family of immune system receptors and the immune system’s first line of defense, recognize pathogens and initiate an immune response. Idera’s DNA and RNA chemistry expertise has generated a pipeline of compounds designed to interact with specific TLRs for a broad range of diseases. Through its internal pipeline and collaborative alliances, Idera has established a portfolio of TLR-targeted therapeutic candidates for infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. 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; whether results obtained in preclinical and clinical studies such as the studies 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 Quarterly Report on Form 10-Q for the three months ended September 30, 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
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Idera Pharmaceuticals, Inc. (Nasdaq: IDRA) announced today preliminary data from a 4-week dose-ranging Phase 1 clinical trial of IMO-2125 in combination with ribavirin in 60 treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection. In the trial, treatment with IMO-2125 in combination with ribavirin was well tolerated and achieved substantial decline in virus levels at two days after the first dose of IMO-2125 and after four weeks of treatment. IMO-2125 is a Toll-like Receptor 9 (TLR9) agonist which stimulates production of natural interferons and other antiviral cytokines
"In this study, IMO-2125 plus ribavirin was well tolerated with no treatment-related discontinuations, and demonstrated substantial antiviral activity," said Robert Arbeit, M.D., Vice President of Clinical Development at Idera. "We believe that IMO-2125 may provide an alternative immune modulatory component to pegylated interferons in the anticipated HCV therapy combinations using direct-acting antivirals. In this treatment scenario, effective stimulation of the host immune system through TLR activation could minimize the risk of viral breakthrough.”
"Based on the overall data from this trial and our Phase 1 clinical trial of IMO-2125 in null-responder HCV patients, our next step in clinical development will be a 12-week Phase 2 trial of IMO-2125 in combination with ribavirin in treatment-naïve HCV patients,” said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. “We expect that the objectives of the Phase 2 study will be to determine optimal dosing, provide longer-term safety data and generate additional antiviral activity data in support of the future clinical development of IMO-2125.”
IMO-2125 Phase 1 Clinical Trial in Treatment-naïve Genotype 1 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 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 current standard of care treatment (Pegasys® plus ribavirin).
Study Results:
Safety
• Treatment with IMO-2125 in combination with ribavirin was well tolerated at all dose levels for 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 flu-like symptoms and injection site reactions.
• Of the 12 patients receiving the standard of care therapy in this trial, neutropenia requiring intervention occurred in two patients and platelet counts dropped below the normal range during the treatment period in seven patients. None of the 48 patients receiving IMO-2125 had neutropenia requiring intervention, and four of the 48 IMO-2125 patients had platelet counts drop below the normal range during the treatment period.
Antiviral Activity
• IMO-2125 induced substantial declines in viral levels at two days after the first dose at all dose levels.
• At the mid-week evaluation in the fourth week of treatment, mean viral load reductions with the three higher-dose IMO-2125 regimens ranged from -2.0 to -3.4 log10. Patients who received Pegasys® plus ribavirin achieved a mean viral load reduction of -3.8 log10 at the same timepoint.
• At the end of the fourth week of treatment, mean viral load reductions with the three higher-dose IMO-2125 regimens ranged from -0.6 to -2.4 log10. The mean viral load reduction for patients treated with Pegasys® plus ribavirin at the end of the fourth week of treatment was -3.4 log10.
• The initial dose level in this Phase 1 safety trial, 0.08 mg/kg/week, produced minimal changes in viral load although liver enzyme decreases were observed.
• Liver enzymes (AST/ALT) decreased during the treatment period and were within the normal range by the end of the fourth week of treatment in the majority of IMO-2125-treated patients.
• There was unequal distribution among the treatment groups of patients with poor prognostic factors at baseline, including CT or TT IL28B genotype, IP-10 values >600 pg/mL, and older age.
The Company plans to present detailed results of this study at a scientific meeting in 2011.
Planned Phase 2 Clinical Trial
In the planned 12-week Phase 2 randomized clinical trial, patients will be stratified for IL28B genotype (CC vs. CT/TT) and will receive either IMO-2125 plus ribavirin or Pegasys® plus ribavirin. The Company plans for recruitment of this clinical trial to start in the first quarter of 2011, pending regulatory concurrence. The Company expects that the objective of this clinical trial will be to provide the basis for subsequent clinical development of IMO-2125 as an alternative to pegylated-interferon in triple combination therapy with ribavirin and a direct-acting antiviral.
IMO-2125 Monotherapy Phase 1 Clinical Trial in Null-Responder HCV Patients
IMO-2125 has also been evaluated in a Phase 1 clinical trial in 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at one of five dose levels and 10 patients received placebo once per week for four weeks. Interim safety, antiviral activity and mechanism of action data were presented for the once-weekly dosing regimens in April 2010 at the Annual Meeting of the European Association for the Study of the Liver and complete data were presented in October 2010 at the Annual Meeting of the American Association for the Study of Liver Diseases.
Seven patients were enrolled in an additional cohort to evaluate twice-weekly dosing of IMO-2125 at 0.16 mg/kg/dose. Consistent with the patients’ null-responder status, 6 of 7 patients had CT or TT IL28B genotype. There were no treatment-related serious adverse events or discontinuations. As previously observed, the most common adverse events were injection site reactions and flu-like symptoms. Three patients in this cohort achieved greater than 1 log10 reduction, ranging from -1.9 to -3.5 log10, in viral load at least once during the treatment period. One of the patients with CT genotype achieved HCV viral levels at the lower limit of quantification (100 copies/mL) at Day 29, four days after the last IMO-2125 dose.
“We are pleased that the results of our Phase 1 clinical trials have shown that IMO-2125 stimulates the immune system in a manner consistent with the intended TLR9 agonist mechanism of action, and that this biological activity has led to reductions in HCV viral load,” said Tim Sullivan, Vice President of Development Programs and Alliance Management at Idera. “IMO-2125 was designed using our chemistry-based approach to optimize the activity of TLR-targeted drug candidates.”
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, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, 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 is developing drug candidates that act by modulating immune responses through specific Toll-like Receptors (TLRs). TLRs, a family of immune system receptors and the immune system’s first line of defense, recognize pathogens and initiate an immune response. Idera’s DNA and RNA chemistry expertise has generated a pipeline of compounds designed to interact with specific TLRs for a broad range of diseases. Through its internal pipeline and collaborative alliances, Idera has established a portfolio of TLR-targeted therapeutic candidates for infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. 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; whether results obtained in preclinical and clinical studies such as the studies 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 Quarterly Report on Form 10-Q for the three months ended September 30, 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
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
October 30, 2010
Idera Pharmaceuticals Presents Phase 1 Data on IMO-2125 Demonstrating Induction of Broad Antiviral Immune Response in Null-Responder HCV Patients
CAMBRIDGE, Mass., Oct 30, 2010 (BUSINESS WIRE) -- Idera Pharmaceuticals, Inc. /quotes/comstock/15*!idra/quotes/nls/idra (IDRA 2.76, -0.03, -1.08%) announced today the presentation of data from a Phase 1 clinical trial evaluating IMO-2125, a novel immune modulator, in null-responder patients with chronic hepatitis C virus (HCV) infection. The oral presentation, entitled "IMO-2125, a TLR9 Agonist, Induces Immune Responses which Correlate with Reductions in Viral Load in Null-Responder HCV Patients" (Abstract #33), is being made by Maribel Rodriguez-Torres, M.D., of Fundacion de Investigacion in Santurce, Puerto Rico at the 61st Annual Meeting of the American Association for the Study of Liver Diseases (AASLD).
"Null-responder patients are the most difficult HCV patients to treat and represent an area of significant need as there are currently no approved treatment options for these patients," said Dr. Rodriguez-Torres. "The data presented show that IMO-2125 induced a broad immune response including induction of endogenous interferons. This suggests that IMO-2125 may provide an alternative to the recombinant interferon component of HCV treatment."
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at five dose levels and 10 patients received placebo once per week for four weeks. Most of these patients were infected with HCV genotype 1 and had the CT or TT IL28B gene alleles. IMO-2125 was well tolerated at all dose levels. IMO-2125 induced a broad immune response with dose-dependent increases in serum concentrations of antiviral proteins and activation of cellular immune responses. Across the three highest dose levels, seventy-five percent of patients achieved a 1 log10 or greater decrease in viral load at least once during the treatment period. Consistent with the proposed mechanism of IMO-2125, induction of higher serum concentrations of interferon-alpha correlated with greater decreases in HCV viral load. Additional patients are being enrolled in this Phase 1 trial to evaluate twice-weekly dosing of IMO-2125.
"These data demonstrate that in the trial once-weekly dosing of IMO-2125 in null-responders induced a distinctive pattern of immune activation and achieved dose-dependent viral load reductions," said Robert Arbeit, M.D., VP of Clinical Development of Idera Pharmaceuticals. "To optimize the dosing schedule and maximize antiviral activity we are continuing the trial to evaluate twice-weekly dosing of IMO-2125."
Dr. Arbeit continued, "In addition, we are conducting a Phase 1 trial in treatment-naive HCV patients evaluating IMO-2125 at multiple dose levels using both once-weekly and twice-weekly dosing regimens for four weeks in combination with ribavirin, compared to a control arm of patients receiving pegylated recombinant interferon-alpha and ribavirin. We expect to report top-line data from this trial in the fourth quarter."
"The data presented from this trial support the target product profile of IMO-2125 as a novel immune modulator with the potential to be used as a key component of HCV treatment," said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. "Prior to initiating a Phase 2 clinical trial for IMO-2125, we plan to analyze the full data sets from the ongoing Phase 1 IMO-2125 trials and evaluate the upcoming changes in the development and treatment landscape for HCV. We expect that, after assessing these factors, we will outline our clinical development strategy and plans for a Phase 2 program for IMO-2125 by the end of 2010."
Phase 1 Clinical Trial in Null-Responder HCV Patients
Study Design:
IMO-2125 was administered subcutaneously once per week for four weeks at five dose levels of 0.04, 0.08, 0.16, 0.32 and 0.48 mg/kg. The clinical trial was designed to evaluate safety, immunological activity and reduction in HCV viral load. Eight patients were enrolled at each dose level with an additional two patients randomized to receive placebo treatment for a total of 10 per cohort. All patients enrolled in the trial were null-responders, defined as patients who failed to achieve a 2 log10 reduction in viral load with 12 to 24 weeks of previous treatment with pegylated recombinant interferon-alpha plus ribavirin.
Study Results:
Patient Population
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy and 10 patients received placebo. Patients were predominantly infected with HCV genotype 1 (98%) and over 90% were IL-28B genotypes CT or TT. At enrollment, the patients had high viral load (mean HCV RNA, 6.8 log10) and elevated levels of IP-10 (mean, 561 pg/mL). These factors are generally associated with poor response to standard of care treatment.
Safety
IMO-2125 was well tolerated for four weeks of treatment. There were no treatment-related serious adverse events (SAEs) and no treatment-related discontinuations. The most common adverse events were "flu-like symptoms" that typically lasted less than 1 day, injection site reactions and headache. There were no clinically significant adverse effects on safety laboratory parameters.
IMO-2125 Activation of Immune Response
Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of endogenous interferon-alpha, which were more pronounced after the fourth dose compared to the first dose. Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of IP-10 and 2', 5'-oligoadenylate synthetase (2', 5'-OAS), host proteins which are known to contribute to antiviral activity. Patients receiving IMO-2125 showed dose-dependent increases in cell markers of immune activation, including increases in NK cells, helper T cells and cytotoxic T cells.
HCV RNA reduction
Patients receiving IMO-2125 showed dose-dependent reduction in HCV RNA viral load. At dose levels of 0.32 and 0.48 mg/kg/week, six of eight patients and seven of eight patients, respectively, achieved a reduction in viral load of 1 log10 or more at least once during the treatment period; in both groups the median for the maximum viral load reductions was 1.6 log10. IL28B genotype data are available for 14 of the 16 patients treated with IMO-2125 at 0.32 or 0.48 mg/kg/week. Thirteen of these patients had CT or TT IL28B genotype, of which 10 had maximum viral load reductions ranging from -1 to -2.6 log10 at least once during the treatment period. The 14th patient had CC IL28B genotype and had a maximum viral load reduction of 2.5 log10 at least once during the treatment period. Serum concentrations of endogenous interferon-alpha induced by IMO-2125 treatment correlated with reductions in HCV RNA viral levels.
Authors of the presentation and study investigators include: Maribel Rodriguez-Torres, M.D., of Fundacion de Investigation, Santurce PR; Reem Ghalib, M.D., of The Liver Institute, Dallas TX; Stuart Gordon, M.D., of Henry Ford Medical Center, Novi, MI; Eric Lawitz, M.D., of Alamo Medical Research, San Antonio TX; Keyur Patel, M.D., of Duke University Medical Center, Durham NC; Ronald Pruitt, M.D., of Nashville Gastrointestinal Specialists, Nashville, TN; Aasim Sheikh, M.D., of Gastrointestinal Specialists of Georgia, Marietta GA; Andrew Muir, M.D., MHS, of Duke Clinical Research Institute, Durham, NC; John McHutchison, M.D., formerly of Duke Clinical Research Institute, Durham, NC; and Alice Bexon, MBChB, Ekambar Kandimalla, Ph.D., Melissa Precopio, Ph.D. and Tim Sullivan, Ph.D., of Idera Pharmaceuticals, Inc.
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 is currently in a Phase 1 clinical trial in null-responder HCV patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks. IMO-2125 is also being evaluated in a Phase 1 clinical trial in treatment-naive HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are designed to modulate specific Toll-like Receptors (TLRs), which are a family of immune system receptors that direct immune system responses. Our pioneering DNA and RNA chemistry expertise enables us to create drug candidates for our internal development programs and our partnered programs, and generates opportunities for additional 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; whether results obtained in preclinical studies and early clinical trials such as the 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 Quarterly Report on Form 10-Q for the three months ended June 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
SOURCE: Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
"Null-responder patients are the most difficult HCV patients to treat and represent an area of significant need as there are currently no approved treatment options for these patients," said Dr. Rodriguez-Torres. "The data presented show that IMO-2125 induced a broad immune response including induction of endogenous interferons. This suggests that IMO-2125 may provide an alternative to the recombinant interferon component of HCV treatment."
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy at five dose levels and 10 patients received placebo once per week for four weeks. Most of these patients were infected with HCV genotype 1 and had the CT or TT IL28B gene alleles. IMO-2125 was well tolerated at all dose levels. IMO-2125 induced a broad immune response with dose-dependent increases in serum concentrations of antiviral proteins and activation of cellular immune responses. Across the three highest dose levels, seventy-five percent of patients achieved a 1 log10 or greater decrease in viral load at least once during the treatment period. Consistent with the proposed mechanism of IMO-2125, induction of higher serum concentrations of interferon-alpha correlated with greater decreases in HCV viral load. Additional patients are being enrolled in this Phase 1 trial to evaluate twice-weekly dosing of IMO-2125.
"These data demonstrate that in the trial once-weekly dosing of IMO-2125 in null-responders induced a distinctive pattern of immune activation and achieved dose-dependent viral load reductions," said Robert Arbeit, M.D., VP of Clinical Development of Idera Pharmaceuticals. "To optimize the dosing schedule and maximize antiviral activity we are continuing the trial to evaluate twice-weekly dosing of IMO-2125."
Dr. Arbeit continued, "In addition, we are conducting a Phase 1 trial in treatment-naive HCV patients evaluating IMO-2125 at multiple dose levels using both once-weekly and twice-weekly dosing regimens for four weeks in combination with ribavirin, compared to a control arm of patients receiving pegylated recombinant interferon-alpha and ribavirin. We expect to report top-line data from this trial in the fourth quarter."
"The data presented from this trial support the target product profile of IMO-2125 as a novel immune modulator with the potential to be used as a key component of HCV treatment," said Sudhir Agrawal, D.Phil., Chairman and Chief Executive Officer at Idera. "Prior to initiating a Phase 2 clinical trial for IMO-2125, we plan to analyze the full data sets from the ongoing Phase 1 IMO-2125 trials and evaluate the upcoming changes in the development and treatment landscape for HCV. We expect that, after assessing these factors, we will outline our clinical development strategy and plans for a Phase 2 program for IMO-2125 by the end of 2010."
Phase 1 Clinical Trial in Null-Responder HCV Patients
Study Design:
IMO-2125 was administered subcutaneously once per week for four weeks at five dose levels of 0.04, 0.08, 0.16, 0.32 and 0.48 mg/kg. The clinical trial was designed to evaluate safety, immunological activity and reduction in HCV viral load. Eight patients were enrolled at each dose level with an additional two patients randomized to receive placebo treatment for a total of 10 per cohort. All patients enrolled in the trial were null-responders, defined as patients who failed to achieve a 2 log10 reduction in viral load with 12 to 24 weeks of previous treatment with pegylated recombinant interferon-alpha plus ribavirin.
Study Results:
Patient Population
This Phase 1 clinical trial evaluated 51 null-responder HCV patients; 41 patients received IMO-2125 monotherapy and 10 patients received placebo. Patients were predominantly infected with HCV genotype 1 (98%) and over 90% were IL-28B genotypes CT or TT. At enrollment, the patients had high viral load (mean HCV RNA, 6.8 log10) and elevated levels of IP-10 (mean, 561 pg/mL). These factors are generally associated with poor response to standard of care treatment.
Safety
IMO-2125 was well tolerated for four weeks of treatment. There were no treatment-related serious adverse events (SAEs) and no treatment-related discontinuations. The most common adverse events were "flu-like symptoms" that typically lasted less than 1 day, injection site reactions and headache. There were no clinically significant adverse effects on safety laboratory parameters.
IMO-2125 Activation of Immune Response
Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of endogenous interferon-alpha, which were more pronounced after the fourth dose compared to the first dose. Patients receiving IMO-2125 showed dose-dependent increases in serum concentrations of IP-10 and 2', 5'-oligoadenylate synthetase (2', 5'-OAS), host proteins which are known to contribute to antiviral activity. Patients receiving IMO-2125 showed dose-dependent increases in cell markers of immune activation, including increases in NK cells, helper T cells and cytotoxic T cells.
HCV RNA reduction
Patients receiving IMO-2125 showed dose-dependent reduction in HCV RNA viral load. At dose levels of 0.32 and 0.48 mg/kg/week, six of eight patients and seven of eight patients, respectively, achieved a reduction in viral load of 1 log10 or more at least once during the treatment period; in both groups the median for the maximum viral load reductions was 1.6 log10. IL28B genotype data are available for 14 of the 16 patients treated with IMO-2125 at 0.32 or 0.48 mg/kg/week. Thirteen of these patients had CT or TT IL28B genotype, of which 10 had maximum viral load reductions ranging from -1 to -2.6 log10 at least once during the treatment period. The 14th patient had CC IL28B genotype and had a maximum viral load reduction of 2.5 log10 at least once during the treatment period. Serum concentrations of endogenous interferon-alpha induced by IMO-2125 treatment correlated with reductions in HCV RNA viral levels.
Authors of the presentation and study investigators include: Maribel Rodriguez-Torres, M.D., of Fundacion de Investigation, Santurce PR; Reem Ghalib, M.D., of The Liver Institute, Dallas TX; Stuart Gordon, M.D., of Henry Ford Medical Center, Novi, MI; Eric Lawitz, M.D., of Alamo Medical Research, San Antonio TX; Keyur Patel, M.D., of Duke University Medical Center, Durham NC; Ronald Pruitt, M.D., of Nashville Gastrointestinal Specialists, Nashville, TN; Aasim Sheikh, M.D., of Gastrointestinal Specialists of Georgia, Marietta GA; Andrew Muir, M.D., MHS, of Duke Clinical Research Institute, Durham, NC; John McHutchison, M.D., formerly of Duke Clinical Research Institute, Durham, NC; and Alice Bexon, MBChB, Ekambar Kandimalla, Ph.D., Melissa Precopio, Ph.D. and Tim Sullivan, Ph.D., of Idera Pharmaceuticals, Inc.
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 is currently in a Phase 1 clinical trial in null-responder HCV patients, defined as those who did not achieve a 2 log10 reduction with prior standard of care treatment, as monotherapy for 4 weeks. IMO-2125 is also being evaluated in a Phase 1 clinical trial in treatment-naive HCV patients in combination with ribavirin for 4 weeks.
About Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals develops drug candidates to treat infectious diseases, autoimmune and inflammatory diseases, cancer, and respiratory diseases, and for use as vaccine adjuvants. Our proprietary drug candidates are designed to modulate specific Toll-like Receptors (TLRs), which are a family of immune system receptors that direct immune system responses. Our pioneering DNA and RNA chemistry expertise enables us to create drug candidates for our internal development programs and our partnered programs, and generates opportunities for additional 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; whether results obtained in preclinical studies and early clinical trials such as the 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 Quarterly Report on Form 10-Q for the three months ended June 30, 2010, which important factors are incorporated herein by reference. Idera disclaims any intention or obligation to update any forward-looking statements.
SOURCE: Idera Pharmaceuticals, Inc.
Idera Pharmaceuticals, Inc.
Teri Dahlman, 617-679-5519
tdahlman@iderapharma.com
or
MacDougall Biomedical Communications
Chris Erdman, 781-235-3060
cerdman@macbiocom.com
Source
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