Psoriasis Drug Shows Promise in Mid-Stage Trial
Toll-like receptor antagonist meets primary endpoint of safety and tolerability
Positive results have been reported from a randomized, double-blind, placebo-controlled phase II trial of IMO-8400 (Idera Pharmaceuticals) in 32 patients with moderate-to-severe plaque psoriasis.
The study’s primary endpoint was to evaluate the safety and tolerability of IMO-8400 over a 12-week treatment period. A secondary objective was to evaluate the clinical activity of IMO-8400.
The trial met its primary endpoint as all treatments were well-tolerated, with no treatment-related discontinuations, serious adverse events, or dose reductions.
Treatment with IMO-8400 also met the secondary objective of demonstrating clinical activity in patients with psoriasis, as assessed by the Psoriasis Area and Severity Index (PASI).
IMO-8400 is an antagonist of Toll-like receptors (TLRs) 7, 8, and 9. It is being developed for the treatment of genetically defined forms of B-cell lymphoma and orphan autoimmune diseases. Among patients who completed 12 weeks of treatment, PASI 50 (i.e., 50% improvement compared with baseline PASI) was achieved in nine of 20 (45%) who received IMO-8400 at any dose level compared with one of seven (14%) who received placebo. PASI 75 (i.e., 75% improvement compared with baseline PASI) was achieved in four (20%) patients treated with IMO-8400 at any dose level, and in zero placebo patients.
In the phase II study, all of the patients were withdrawn from prior therapies with an appropriate wash-out period. The patients were then randomly assigned to receive subcutaneous IMO-8400 monotherapy (at dose levels of 0.075 mg/kg, 0.15 mg/kg, and 0.3 mg/kg) or placebo weekly for 12 weeks, with a 6-week follow-up period.
In addition, in October 2013 the phase II trial was expanded to evaluate a dose of 0.6 mg/kg once weekly versus placebo in 12 patients. This trial is being conducted in the Netherlands. Data from this expanded study are expected to be available by the end of the second quarter of 2014.
IMO-8400 is a first-in-class synthetic oligonucleotide-based antagonist of Toll-like receptors (TLRs) 7, 8, and 9. The compound has shown activity in preclinical models of autoimmune diseases, including psoriasis, lupus, and arthritis.
IMO-8400 was well-tolerated in a phase I trial involving 42 healthy subjects who received single and multiple escalating doses up to 0.6 mg/kg for 4 weeks, and it has shown the ability to inhibit immune responses mediated by TLRs 7, 8, and 9. The drug is being developed for the treatment of genetically defined forms of B-cell lymphoma, including Waldenström’s macroglobulinemia and diffuse large B-cell lymphoma, and orphan autoimmune diseases, including polymyositis and dermatomyositis.
Source: Idera Pharmaceuticals; March 28, 2014.