Idera Announces Presentation of Positive Data from Phase 2 Trial of TLR 7 and 9 Antagonist in Patients with Moderate-to-Severe Plaque Psoriasis
PASI Score Improvements Correlated with Downregulation of IL-17 Pathway
“TLR antagonism provides a novel mechanism of action for the potential treatment of patients with moderate to severe plaque psoriasis. Clinical activity demonstrated in this four-week proof-of-concept trial encourages further development of TLR antagonists over longer treatment periods,” said Dr. Kimball.
“We are very pleased that the clinical improvements observed in
psoriasis patients treated with IMO-3100 for four weeks correlated with
the proposed mechanism of action for TLR antagonism in autoimmune
diseases,” said
Data from the Phase 2 Trial
The objectives of the Phase 2 trial of IMO-3100 were to evaluate the
safety and tolerability and to evaluate the clinical activity of TLR
antagonism in patients with psoriasis after four weeks of treatment.
Top-line data from this trial was announced in
Safety:
- Treatment with IMO-3100 was well tolerated at both dose levels studied
- There were no treatment-related discontinuations or changes in laboratory parameters
Clinical Activity:
- On day 57, 48% of patients treated with either dose of IMO-3100 (12 of 25) demonstrated statistically significant improvements of 35% to 90% from baseline PASI scores compared with 0 of 12 in the placebo cohort (p<0.005)
- Rapid improvement in PASI scores was observed in IMO-3100 treated patients compared to placebo-treated patients; Improvement in PASI was sustained through five weeks after the last dose
- The pre-specified clinical endpoint of reduction in PASI score at day 29 was achieved with statistical significance in the 0.16 mg/kg cohort (p<0.02 compared to placebo) but not in the 0.32 mg/kg cohort
- PASI 50 was achieved in 7 of 25 patients treated with IMO-3100 (3 of 12 at 0.16 mg/kg and 4 of 13 at 0.32 mg/kg), compared to 0 of 12 placebo treated patients (p<0.05); PASI 75 was achieved in 1 patient in each IMO-3100 cohort during the trial period
- The pre-specified clinical endpoint of improvement in induration, a measure of plaque thickness, at day 29 was achieved with statistical significance in the 0.16 mg/kg cohort (p<0.02) compared to placebo-treated patients
Mechanism of Action Based on Analysis of Skin Biopsies:
- Median change in epidermal thickness (the histologically defined primary endpoint of the trial) was -6.4% in IMO-3100 treated patients compared to +7.7% in placebo treated patients, representing a favorable, but not statistically significant, trend. A known limitation of skin biopsies after four weeks of treatment is that psoriatic plaques do not resolve in a uniform fashion, and therefore, biopsies may not provide a representative sampling of lesions (ref: Ann Rheum Dis 2005;64:65-68)
- Representative patients treated with IMO-3100 showed K16 staining (marker of keratinocyte proliferation) reverting toward normal and decreasing infiltrates of CD3+ lymphocytes and CD11c+ cells
-
DNA microarray analysis of biopsies from the IMO-3100 treated patients
compared to placebo treated patients (n=6 each) showed significant
improvement (p<10-6) in psoriasis disease-associated
genes (Tian et al, PLoS ONE,
Sep 2012 ) and of genes unique to the IL-17 pathway, which is central to the pathogenesis of psoriasis. Detailed data will be presented at a future scientific meeting.
About the Phase 2 Trial in Psoriasis
The Phase 2 trial was a randomized, double-blind, placebo-controlled
trial of IMO-3100 in patients with moderate-to-severe plaque psoriasis.
In the trial, 44 patients at 11 centers in
Next Step in Autoimmune Disease Program
Based on the clinical activity of IMO-3100 observed in patients with
psoriasis, and the comparative profiles of IMO-3100 and IMO-8400,
including the inhibition of TLR8 by IMO-8400, Idera has determined that
the next step is to conduct a Phase 2 clinical trial of IMO-8400 in
patients with psoriasis with a treatment period of up to 12 weeks. In
this trial, 32 patients would be randomized to receive weekly doses for
up to 12 weeks at one of three dose levels of IMO-8400 or placebo. This
Phase 2 protocol has been approved by the Centrale Commisse Mensgebonden
Onderzoek of
About TLRs and Idera's Pipeline
Toll-like Receptors (TLRs) play a key role in inflammation and immunity. Idera is developing compounds targeted to TLRs 3, 7, 8, and 9, which are expressed in different cells and serve unique functions. Using its chemistry-based approach, Idera has created novel drug candidates that modulate immune responses through either activation or inhibition of specific TLRs. In autoimmune diseases, immune complexes containing self-nucleic acids activate TLRs 7, 8, and 9 and induce multiple cytokines that cause further damage to the body's own tissues and organs, thereby releasing more self-nucleic acids. Inhibition of specific TLRs may be useful in treating autoimmune diseases, such as systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis, by blocking the induction of multiple cytokines and signaling pathways. Idera's clinical candidates for application in autoimmune diseases are IMO-3100, an antagonist of TLR7 and TLR9, and IMO-8400, an antagonist of TLRs 7, 8, and 9.
About Psoriasis
Psoriasis is a systemic immune-mediated disorder, characterized by inflammatory skin and joint manifestations. The most common form, plaque psoriasis, appears as raised, red patches covered with a silvery white buildup of dead skin cells. Psoriasis can occur on any part of the body and is associated with other serious health conditions, such as diabetes, heart disease and depression.
Psoriasis is the most prevalent autoimmune disease in the U.S.,
according to the
About IID 2013
International Investigative Dermatology 2013 (IID 2013) brings together
the
About
Idera Forward Looking Statements
This press release contains forward-looking statements concerning
Source:
Idera Pharmaceuticals, Inc.
Lou Arcudi, 617-679-5517
larcudi@iderapharma.com