Health Boards
Idera Pharmaceuticals today announced that 48% of patients with moderate-to-severe plaque psoriasis (12 of 25) treated with IMO-3100, a selective antagonist of Toll-like Receptors (TLRs) 7 and 9, demonstrated improvements in Psoriasis Area Severity Index (PASI) scores of 35% to 90% from baseline at the completion of a randomized, double-blind, placebo-controlled Phase 2a clinical trial of two dose levels of IMO-3100 administered for four weeks, with a four-week follow-up period. None of the 12 placebo-treated patients had improvement in this range; this difference was statistically significant (p<0.005). The Company believes the results of this trial provide clinical proof-of-concept for the mechanism of action of selective TLR inhibition in patients with psoriasis and potentially other autoimmune and inflammatory disorders.
“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 Alexa Kimball, M.D., M.P.H., Vice Chair, Department of Dermatology at Massachusetts General Hospital, Boston, and an investigator in the trial.
“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 James Krueger, M.D., Ph.D., of The Rockefeller University, New York. “We are excited to see these data, which demonstrate the translation of targeting a novel mechanism of action into clinical activity and support further studies of TLR antagonists for the treatment of psoriasis. Our laboratory is continuing to evaluate the immunological pathways by which TLR antagonists suppress the signaling cascades that underlie psoriasis and have the potential to open up a new approach to disease treatment.”
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 (PGA) scores. In addition to the clinical assessments, biopsies of psoriasis plaques were evaluated for treatment-related changes in epidermal thickness and immune cell infiltrates consistent with the intended mechanism of action. Patients were enrolled at eleven sites in the United States.
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 Sudhir Agrawal, D. Phil., Chief Executive Officer of Idera. “The insights gained from this trial support expansion of our TLR antagonist program for the treatment of autoimmune diseases. In 2013, we plan to advance the clinical development of a selective TLR antagonist for the treatment of moderate-to-severe plaque psoriasis and also for the treatment of lupus.”
Source: iderapharma.com
Previous thread on IMO-3100: Idera announce phase 2 trial of IMO-3100
“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 Alexa Kimball, M.D., M.P.H., Vice Chair, Department of Dermatology at Massachusetts General Hospital, Boston, and an investigator in the trial.
“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 James Krueger, M.D., Ph.D., of The Rockefeller University, New York. “We are excited to see these data, which demonstrate the translation of targeting a novel mechanism of action into clinical activity and support further studies of TLR antagonists for the treatment of psoriasis. Our laboratory is continuing to evaluate the immunological pathways by which TLR antagonists suppress the signaling cascades that underlie psoriasis and have the potential to open up a new approach to disease treatment.”
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 (PGA) scores. In addition to the clinical assessments, biopsies of psoriasis plaques were evaluated for treatment-related changes in epidermal thickness and immune cell infiltrates consistent with the intended mechanism of action. Patients were enrolled at eleven sites in the United States.
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 Sudhir Agrawal, D. Phil., Chief Executive Officer of Idera. “The insights gained from this trial support expansion of our TLR antagonist program for the treatment of autoimmune diseases. In 2013, we plan to advance the clinical development of a selective TLR antagonist for the treatment of moderate-to-severe plaque psoriasis and also for the treatment of lupus.”
Source: iderapharma.com
Previous thread on IMO-3100: Idera announce phase 2 trial of IMO-3100
