Abbott Laboratories presented data at the American College of Rheumatology meeting in New Orleans from pivotal Phase III and ongoing trials of Humira (adalimumab), developed in collaboration with Cambridge Antibody Technology Group plc, of Melbourn, UK.
Also called D2E7, Humira is Abbott Park, Ill.-based Abbott's investigational fully human monoclonal antibody submitted in April to the FDA and European regulatory authorities. The filings were based on 23 studies involving more than 2,300 patients in North America.
Data released at the meeting included an evaluation of the safety and efficacy profiles for Humira at a dose of 40 mg every other week in rheumatoid arthritis (RA), including inhibition of the progression of structural joint damage, maintenance of response after three years and impact on patients' quality of life.
A pivotal Phase III study, designed to evaluate inhibition of radiographic progression of RA by showing changes in X-rays, met its primary endpoints. The 52-week study compared Humira to placebo, both in combination with methotrexate (MTX). The mean change for patients receiving Humira plus MTX was 0.1 in the Sharp X-ray score, compared with 2.7 for patients receiving placebo plus MTX.
In another long-term extension study, 64 percent of patients receiving Humira at three years achieved the American College of Rheumatology (ACR) 20 response and 24 percent achieved an ACR 70 response.
In a 52-week, quality-of-life study, patients receiving Humira 40 mg every other week with MTX had a 0.59 mean change from baseline compared to a 0.25 mean change from baseline for patients receiving placebo plus MTX, a statistically significant difference. In the largest, controlled TNF-antagonist safety study of 636 patients with RA, patients receiving Humira plus the standard of care and those receiving placebo and standard of care had similar rates of adverse events, serious adverse events, infections and serious infections.
In other news from the conference:
• Amgen Inc., of Thousand Oaks, Calif., reported data from a study evaluating the ability of Kineret (anakinra) to inhibit bone and joint damage in 906 adult RA patients. In a 12-month, double-blind study, Kineret-treated patients experienced 36 percent less bone and joint destruction as measured by total modified Sharp scores than patients treated with placebo plus methotrexate (p<0.001). At week 52, 50 percent of Kineret patients had no disease progression compared with 42 percent of placebo patients (p=0.018), and fewer Kineret patients had severe disease progression than placebo patients (12 percent vs. 19 percent, p=0.003). A reduction in progression was seen in joint erosion and joint space narrowing. Separately, results from a 205-patient, Phase III study of Amgen's fully human TNF receptor, Enbrel (etanercept), demonstrated significant inhibition in the progression of structural damage in patients with psoriatic arthritis. New data from an ongoing study of patients with early erosive rheumatoid arthritis demonstrated that Enbrel provided sustained improvement in signs and symptoms over four years. Also, 58 percent of 142 patients who remained on Enbrel for three years had no radiographic progression of disease.
• The Arizona Arthritis Center at the University of Arizona College of Medicine in Tucson reported that patients with immune-mediated inflammatory disorders who are treated with infliximab (Centocor Inc.'s Remicade) were twice as likely to remain on therapy as those treated with Enbrel. Data from the 242-patient study found 63 percent of those treated with Enbrel (61 of 96) discontinued therapy compared to 28 percent (41 of 146) in the infliximab group. Lack of efficacy, adverse events and patient preference were among the top reasons cited for discontinuation.
• Centocor Inc., of Malvern, Pa., reported data from the randomized, double-blind, placebo-controlled, 101-patient IMPACT trial (Infliximab Multinational Psoriatic Arthritis Controlled Trial), assessing the efficacy and safety of Remicade in treating patients with psoriatic arthritis. Patients given Remicade (5mg/kg) experienced improvement in their joints, as measured by the ACR 20, 50 and 70 response criteria. Among psoriasis patients, the average reduction of the Psoriasis Area and Severity Index (PASI) was 81 percent in the Remicade group compared to an average increase of 36 percent for placebo. Data from another trial showed patients with early rheumatoid arthritis treated with Remicade, in combination with methotrexate, appeared to experience greater inhibition of joint destruction and clinical improvement than patients treated with methotrexate alone. At 54 weeks there were significant differences in the Remicade treatment group in synovitis, bone edema and bone erosions. A separate study showed Remicade can provide a high degree of sustained clinical efficacy for at least one year in patients with active ankylosing spondylitis, a chronic inflammatory rheumatic disease.
• Genentech Inc., of South San Francisco, F. Hoffmann-La Roche Ltd., of Basel, Switzerland, and IDEC Pharmaceuticals Corp., of San Diego, reported preliminary positive interim results from a randomized, double-blind, placebo-controlled, 161-patient Phase II study examining the use of Rituxan (rituximab) to treat RA. Among the 30 patients receiving methotrexate alone, 10 experienced ACR 20 responses, three experienced ACR 50 and none experienced ACR 70. Among the 31 receiving Rituxan alone, 18 experienced ACR 20, 10 experienced ACR 50 and four experienced ACR 70. Among the 31 receiving Rituxan plus cyclophosphamide, 26 experienced ACR 20, 14 experienced ACR 50 and five experienced ACR 70. Among the 30 receiving Rituxan plus methotrexate, 24 experienced ACR 20, 15 experienced ACR 50 and seven experienced ACR 70.
• IBEX Technologies Inc., of Montreal, said it discovered a novel therapeutic target for the treatment of arthritis. The peptide target showed evidence of activating the production of collagenase, an enzyme that destroys cartilage. Separately, IBEX reported study results demonstrating the ability of two of its biomarkers to predict the severity of osteoarthritis progression. Specifically, the biomarkers were able to distinguish between patients who will progress rapidly to more advanced knee osteoarthritis and those who will not. IBEX's stock (TSE:IBT) gained C10 cents Monday, or 26.8 percent, to close at C45 cents.
• Interleukin Genetics Inc., of Waltham, Mass., reported preliminary results of an economic modeling study that indicate the use of pharmacogenetic testing to determine specific IL-1 gene variations may be a cost-effective tool for determining the best course of therapy for RA patients. The study was designed to model the cost effectiveness of the test during the process of prescribing anti-cytokine biologic therapies. Interleukin's stock (NASDAQ:ILGN) gained 4 cents Monday to close at 75 cents.
• La Jolla Pharmaceutical Co., of San Diego, reported preliminary results from the first clinical trial evaluating LJP 1082 to treat antibody-mediated stroke, heart attack, deep-vein thrombosis and recurrent miscarriage. The randomized, placebo-controlled Phase I/II trial, designed to evaluate the safety and activity of a single dose of LJP 1082, also showed that patients receiving higher doses of LJP 1082 had larger reductions in antibodies to LJP 1082. The drug, well tolerated at all five dose levels, had an elimination half-life of at least 12 hours following intravenous administration.
• Scios Inc., of Sunnyvale, Calif., said preclinical study results indicate that SCIO-469, its first-generation oral p38 MAP kinase inhibitor, and SCIO-323, a second-generation p38 MAP kinase inhibitor, reduced clinical severity and radiographic progression of experimental collagen-induced arthritis. SCIO-469 was shown in vitro using human blood cells to block the production of TNF-alpha, IL-1-beta, and COX-2 mRNA in a dose-related manner in response to an inflammatory stimulus.
• Vela Pharmaceuticals Inc., of Lawrenceville, N.J., said it successfully completed its 36-patient Phase II study of very low-dosage cyclobenzaprine. Results indicate that, compared to placebo, very low-dosage cyclobenzaprine (1 mg to 4 mg, taken as a single dose before bedtime) dramatically reduced musculoskeletal pain and fatigue, and improved sleep. No serious adverse events were reported.