ABT-874 Shows Positive Results For Maintenance Of Response In Psoriasis Study
Results from an extension to a Phase II study evaluating the effectiveness of Abbott's investigational anti-IL-12/23 antibody ABT-874 showed that a majority of patients who initially responded to treatment maintained a high level of response following discontinuation of therapy. In the study, patients who achieved 75 percent improvement in psoriasis signs and symptoms (PASI 75) at 12 weeks stopped receiving ABT-874. At 24 weeks, more than two- thirds of these patients maintained at least 50 percent improvement (PASI 50). The Phase II study, conducted in patients with moderate to severe psoriasis, will be presented at the World Congress of Dermatology in Buenos Aires.
Phase II results presented earlier this year at the Society for Investigative Dermatology (SID) Meeting showed ABT-874 reduced psoriasis symptoms significantly in the majority of patients treated. At 12 weeks, at least 90 percent of patients with moderate to severe psoriasis achieved 75 percent improvement in psoriasis signs and symptoms in all but the lowest dosing groups receiving ABT-874, versus 3 percent of patients receiving placebo. Also, more than half of patients achieved 90 percent improvement, in the same four of five ABT-874 dosing groups, versus 0 percent of those receiving placebo.
"ABT-874 represents a novel approach to treating psoriasis, targeting a part of the inflammatory response that is not addressed by any therapy available today," said Alan Menter, MD, Chair, Psoriasis Research, Baylor Research Institute, Dallas. "Data presented earlier this year from this study showed great promise in the ability of ABT-874 to significantly reduce psoriasis symptoms in the majority of patients treated. The study shows positive results for maintenance of a response."
Psoriasis is a chronic autoimmune disease affecting 125 million people worldwide. About 25 percent have moderate to severe disease. The condition speeds the growth cycle of skin cells and results in thick, scaly areas of skin. The most common form of psoriasis, called plaque psoriasis, appears as red, raised areas of skin covered with flaky white scales, which may itch. Psoriasis is more than skin lesions; it may be painful and can impact many aspects of a person's life from professional and social activities to personal relationships. People with psoriasis may also suffer from poor self-image and social isolation. While psoriasis can occur in people of all ages, it typically first appears between the ages of 15 and 35. Currently, there is no cure for psoriasis.
"Abbott is a leader in the development of biologic treatments," said Eugene Sun, M.D., vice president, global pharmaceutical clinical development at Abbott. "Our fully human monoclonal antibody, the world's first, is now approved in four indications around the world and has been submitted for approval in psoriasis and juvenile rheumatoid arthritis. Our scientists are developing additional biologics including ABT-874, which takes a new approach by targeting interleukin-12 and interleukin-23."
Study Background and Results
In a 12-week, double-blind, placebo-controlled study, 180 patients with moderate to severe psoriasis were randomized evenly to six treatment groups: a single, subcutaneous 200-mg injection of ABT-874 at week zero; 100 mg every other week (eow) for 12 weeks; 200 mg weekly for four weeks; 200 mg eow for 12 weeks; 200 mg weekly for 12 weeks; or matching placebo. The primary study endpoint was the proportion of patients achieving 75 percent improvement in the degree and severity of skin lesions after 12 weeks, measured by the Psoriasis Area and Severity Index (PASI).
At least 90 percent of patients achieved PASI 75 at week 12 in all ABT-874 treatment groups except the single-dose group (200 mg at week zero). (Results were, respectively, 63 percent, 93 percent, 90 percent, 93 percent, and 90 percent, vs. 3 percent of those receiving placebo; p<0.001 for all groups.) Also, in the same four treatment groups, more than half of patients achieved 90 percent improvement in skin clearance (results were, respectively, 17 percent, 53 percent, 63 percent, 77 percent, 53 percent, vs. 0 percent of those receiving placebo; p<0.001 for all groups except the single-dose group, 200mg at week 0).
In the continuation of the Phase 2 study, treatment with ABT-874 was discontinued in patients who met the primary endpoint. Maintenance of PASI response was evaluated through Week 48. Results from the first 24 weeks are being reported here.
At 24 weeks, results showed that substantial percentages of PASI 75 responders in the active treatments arms had maintained >/=PASI 50 responses. Results were 68 percent (13 out of 19 patients), 71 percent (20 of 28), 81 percent (22 of 27), 89 percent (25 of 28), and 85 percent (23 of 27) in the five ABT-874 dosing groups, respectively.
The most common adverse events observed were injection site reactions, nasopharyngitis (inflammation of the nose and pharynx), upper respiratory infections, and headache.
Abbott's biologic drugs in development, including ABT-874, are designed to selectively inhibit proteins that are responsible for inflammation. In addition to immune-mediated diseases, Abbott is also researching biologic treatments for cancer and Alzheimer's disease. ABT-874 is a fully human monoclonal antibody designed to target and neutralize interleukin-12 and interleukin-23, two proteins associated with inflammation in psoriasis and other autoimmune disorders. Abbott plans to begin Phase III psoriasis studies with ABT-874 later this year.