Arena Pharmaceuticals announced top-line results from a phase 1b multiple ascending dose clinical trial for APD334, an oral drug candidate that targets the sphingosine 1-phosphate subtype 1 (S1P1) receptor for the potential treatment of autoimmune diseases.
In the phase 1b clinical trial, APD334 demonstrated a dose-dependent effect on lymphocyte count lowering in blood, with mean decreases from baseline of up to 69 per cent. Lymphocyte counts, on average, recovered to baseline within one week of conclusion of dosing. There were no clinically significant safety findings with respect to heart rate or rhythm or pulmonary function, and no clinically significant elevations in liver enzyme tests. The most common treatment-emergent adverse events were mild or moderate contact dermatitis, headache, constipation and diarrhea, with none being clearly drug related. There were no discontinuations for adverse events, and no serious adverse events were observed.
"Lymphocyte lowering at the level demonstrated in this trial has been shown to correlate with clinical efficacy in phase 2 and phase 3 trials of other S1P1 modulators in multiple sclerosis, psoriasis and ulcerative colitis," said William R Shanahan, MD, Arena's senior vice president and chief medical officer. "The results of this trial support investigation of the efficacy and safety of APD334 in patients with autoimmune diseases."
The randomised, double-blind, placebo-controlled phase 1b clinical trial evaluated the safety, tolerability, pharmacodynamics and pharmacokinetics of multiple-ascending doses of APD334. In five different dosing cohorts, a total of 50 healthy volunteers received APD334 and 10 received placebo for 21 days.
"Based on these impressive results, we plan to expedite APD334 into phase 2 clinical trials for ulcerative colitis and Crohn's disease," said Jack Lief, Arena's president and chief executive officer. "The advancement of this promising drug candidate further demonstrates Arena's focused expertise in discovering and developing innovative drug candidates targeting G protein-coupled receptors that have the potential to improve health."
Autoimmune diseases, such as multiple sclerosis, psoriasis, ulcerative colitis, Crohn's disease and rheumatoid arthritis, are characterised by an inappropriate immune response against substances and tissues that are normally present in the body. In an autoimmune reaction, a person's antibodies and immune cells target healthy tissue, triggering an inflammatory response. Reducing the immune and/or inflammatory response is an important goal in the treatment of autoimmune diseases.
APD334 is a potent and selective, orally available investigational drug candidate that targets the S1P1 receptor. Discovered by Arena, APD334 has therapeutic potential in autoimmune diseases. S1P1 receptors have been demonstrated to be involved in the modulation of several biological responses, including lymphocyte trafficking from lymph nodes to the peripheral blood. By isolating lymphocytes in lymph nodes, fewer immune cells are available in the circulating blood to effect tissue damage.