Date: 2014-11-17
Type of information: Presentation of results at a congress
phase: 2b
Announcement: presentation of results at the American College of Rheumatology (ACR) 2014 Annual Meeting taking place in Boston, MA.
Company: Medimmune (USA - MD) global biologics arm of AstraZeneca (UK)
Product: mavrilimumab
Action
mechanism: Mavrilimumab (formerly CAM-3001) is a human monoclonal antibody that targets the alpha receptor for the cytokine granulocyte-macrophage colony-stimulating factor (GM?CSF). Through the targeted blockade of the receptor on the macrophage, a key cell in the pathogenesis of rheumatoid arthritis, mavrilimumab could add a significant new treatment option for RA patients.
Disease: rheumatoid arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country:
Trial details:
Latest
news: * On November 17, 2014, MedImmune, the global biologics research and development arm of AstraZeneca, announced positive results from a Phase IIb study of mavrilimumab, a first-in-class investigational monoclonal antibody for the treatment of rheumatoid arthritis (RA). Study results are being presented in several abstracts at the American College of Rheumatology (ACR) 2014 Annual Meeting taking place in Boston, MA. In the Phase llb study (EARTH EXPLORER-1), 326 patients with moderate and severe RA with an inadequate response to at least one disease-modifying anti-rheumatic drug were randomized to either mavrilimumab (30mg, 100 mg, or 150 mg) plus methotrexate or methotrexate alone (placebo). The study met co-primary endpoints at all mavrilimumab doses. A statistically significant higher percentage of mavrilimumab-treated patients saw improvement in RA symptoms at all doses at week 24 based on ACR 20 measures versus placebo (placebo, 24.7%; 30 mg, 50.6%; 100mg, 61.2%; 150 mg, 73.4%). Statistically significant higher response rates were also seen for the high mavrilimumab dose of 150 mg versus placebo in response rates requiring even greater improvement in symptoms - ACR 50 (placebo, 12.3%; 150 mg, 40.5%) and ACR70 (placebo, 3.7%; 150mg, 13.9%), Low Disease Activity (placebo, 8.6 %; 150 mg, 41.8%). In addition, at week 12, mavrilimumab-treated patients saw statistically significant improvement in joint swelling and tenderness and other RA symptoms at all doses as measured by a numerical decrease in mean DAS28-CRP scores versus placebo (placebo, .7, 30 mg, 1.4; 100 mg, 1.6, 150mg, 1.9.) (#2821 Burmester G, et al. Oral presentation, 2:30PM – 4:00 PM ET Tuesday, November 18, 2014.) In a separate analysis of the data that will be presented at ACR, all mavrilimumab doses produced significant reductions in DAS28-CRP as early as week 1 (the first assessment of treatment response) and this benefit was sustained up to week 24 (study endpoint). In addition, significantly more ACR20 responders occurred in the mavrilimumab 150 mg dose than in the placebo group at week 1 and at every other assessment time point through to week 24. (#1486 McInnes I, et al. General poster session, 8:30 AM – 4:00 PM ET Monday, November 17 2014.) The rapid onset of clinical benefit was mirrored by a reduction in the multi-biomarker disease activity score (MBDA). The MBDA score was calculated using the validated Vectra®DA algorithm, based on serum concentrations of 12 biomarkers also tracked the effect of mavrilimumab on disease over time. Mavrilimumab 150 mg and 100 mg doses showed early (week 1) and sustained (week 24) significant changes in MDBDA score versus placebo. Additional data from EARTH EXPLORER-1 also showed that mavrilimumab treatment produces statistically significant improvements in patient-reported outcomes such as pain, health-related quality of life, physical function, and fatigue compared with placebo. The majority of mavrilimumab patients with improvement in pain and physical function at week 12 sustained these improvements to the end of the study at week 24. (#1485 Kremer J, et al. General poster session 8:30 AM–4:00 PM ET Monday, November 17, 2014)
