Idera Pharmaceuticals Announces Positive Top-line Results from Phase 2 Trial of IMO-3100 in Patients with Moderate-to-Severe Plaque Psoriasis
TLR antagonist achieves statistically significant improvement in PASI scores after four weeks of treatment
Reduction in PASI score sustained for up to four weeks post-treatment
“The clinical activity of IMO-3100 demonstrated in patients with
moderate-to-severe plaque psoriasis is encouraging, especially given the
short duration of treatment in this study that was designed for initial
explorations of safety and efficacy,” commented
“The achievement of statistically significant PASI reductions with only
four weeks of treatment in a placebo-controlled double-blind trial
directly supports the rationale that the modulation of specific TLRs
plays a key role in the treatment of psoriasis and, potentially, other
autoimmune and inflammatory disorders,” commented
About the IMO-3100 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 were randomized to receive IMO-3100
monotherapy at 0.16 or 0.32 mg/kg or placebo by subcutaneous injection
once weekly for four weeks with four weeks of follow-up. Assessments of
safety were performed throughout the treatment and follow-up periods.
Multiple parameters were monitored to assess the clinical activity of
IMO-3100, including Psoriasis Area Severity Index (PASI), mean focal
psoriasis severity and Physician Global Assessment (
Top-line clinical results from this trial include:
- Of the 44 enrolled patients, 40 were clinically evaluable at the end of the four-week treatment period and 37 were evaluable following the four-week follow up period
- Treatment at both IMO-3100 dose levels was well tolerated, with no treatment-related discontinuations
- Among evaluable patients, the median PASI scores at treatment initiation were 14.9, 16.1, and 12.5 in the 0.16 mg/kg, 0.32 mg/kg, and placebo cohorts, respectively
- A treatment effect was demonstrated in measures of clinical efficacy in patients in both IMO-3100 dose cohorts; PASI reductions at both dose levels were sustained throughout the four-week follow-up period
- At the end of the four-week follow-up period, 48% of patients treated with either dose of IMO-3100 (12 of 25) demonstrated improvements of 35% to 90% from baseline PASI scores compared with 0 of 12 in the placebo cohort; this difference was statistically significant (p<0.005)
- The trial achieved the pre-specified clinical endpoint of reduction in PASI scores at the end of treatment in the 0.16 mg/kg dose cohort with statistical significance (p<0.02) compared to the placebo cohort, but not in the 0.32 mg/kg dose cohort
- The 0.16 mg/kg cohort also achieved, with statistical significance (p<0.02), the pre-specified clinical endpoint of improvement in induration, a measure of plaque thickness, at the end of treatment and during the follow-up period
- At the end of the four-week follow-up period, 25% (3 of 12) of patients treated with 0.16 mg/kg dose and 31% (4 of 13) with 0.32 mg/kg dose achieved PASI 50 or greater, compared to 0 of 12 placebo patients
Skin biopsies were collected at baseline and after completion of treatment to investigate changes in epidermal thickness and immune cell infiltrates. Change in epidermal thickness was the primary endpoint for the trial. Placebo treated patients had a median change in epidermal thickness of +7.7% compared to a median change of -6.4% among IMO-3100 treated patients; this difference was not statistically significant. 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).
The Company plans to present complete clinical data from this trial at an upcoming medical meeting.
“We believe this trial in patients with moderate-to-severe plaque
psoriasis provides clinical proof-of-concept for this first-in-class TLR
antagonist, which represents a novel approach to the treatment of
autoimmune diseases. We are very pleased to have observed clinical
responses after only four weeks of treatment,” stated
About TLRs and Idera's Pipeline
Toll-like Receptors (TLRs) play a key role in inflammation and immunity. Of the 10 human TLRs identified to date, 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. Inhibition of specific TLRs may be useful in treating autoimmune disorders, 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.
A characteristic of autoimmune diseases such as SLE and psoriasis is the production of immune complexes with self-nucleic acids. These abnormal immune complexes 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. Thus, a pathologic amplification cycle is established, promoting disease maintenance and progression. In preclinical models of several autoimmune diseases, IMO-3100 and IMO-8400 inhibited TLR-mediated immune responses, interrupted the cycle of disease maintenance and progression through decreases in Th1, Th17 and inflammasome pathways, and led to improvements in multiple measures of disease.
About IMO-3100
IMO-3100, an antagonist of TLR7 and TLR9, is a lead drug candidate in development to treat autoimmune diseases, including psoriasis. In preclinical mouse models of psoriasis, IMO-3100 exerted therapeutic activity by inhibiting disease-associated gene expression and cytokines, such as IL-6, IL-22, IL-17, IL-23, NLRP3 and IL-1β, and proteins in the skin such as S100A7, DEFB4 and LL37. In addition, histological evaluation showed that the psoriatic lesions in IMO-3100-treated animals had reduced epidermal thickness and decreased lymphocyte infiltration compared to control mice.
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
Idera Forward Looking Statements
This press release contains forward-looking statements concerning
Source:
Idera Pharmaceuticals, Inc.
Lou Arcudi, 617-679-5517
larcudi@iderapharma.com