Study met co-primary endpoints, demonstrated rapid and sustained response and statistically significant improvements in patient-reported outcomes
Gaithersburg, MD – November 17, 2014 – MedImmune, the global biologics research and development arm of AstraZeneca, today 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).
Data being presented at ACR shows:
- EARTH EXPLORER I Phase IIb study met co-primary endpoints at all mavrilimumab doses:
- American College of Rheumatology 20 percent improvement criteria (ACR20) at week 24
- Mean change from baseline in the Disease Activity Score 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) at week 12
- All secondary endpoints including ACR50, ACR70 response and DAS28 remission score achieved statistical significance for the high dose of 150 mg.
- Mavrilimumab produced a rapid and sustained improvement in multiple symptoms of rheumatoid arthritis after one week and one dose.
- Statistically significant improvements in patient-reported outcomes such as pain, health-related quality of life, physical function, and fatigue
Mavrilimumab targets the granulocycte-macrophage colony-stimulating factor (GM-CSF) receptor, a key pathway driving macrophage cell activation and the rheumatoid arthritis disease process.
Rheumatoid arthritis is a painful, systemic, chronic inflammatory autoimmune disease which causes damage to the joints and vital organs. The disease affects approximately one in 100 people worldwide and there is still a clear, unmet medical need for some patients, with nearly 40 percent of patients not responding to currently available therapies based on ACR20 criteria.
“Inflammation and autoimmunity include a range of complex diseases such as rheumatoid arthritis, and MedImmune is committed to developing innovative treatments that push the boundaries of science to ultimately provide benefit to patients,” said Dr. Bing Yao, Senior Vice President and Head of the Respiratory, Inflammation and Autoimmunity Innovative Medicines Unit, MedImmune. “We are encouraged by the results of the EARTH EXPLORER I study, which highlight the potential of mavrilimumab to be the first new effective biologic mechanism of action in RA in over 10 years.”
Mavrilimumab had an acceptable tolerability profile, with no apparent safety signals demonstrated over the 24-week study period. The most commonly-reported adverse events (>3 percent) included headache, nasopharyngitis (common cold), hypertension, bronchitis and worsening of RA.
Study Met Co-Primary Endpoints
In the EARTH EXPLORER-1 study, 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.)
Rapid Treatment Response, Improvement in Patient-Reported Outcomes also Seen
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)
“In this important Phase IIb study, mavrilimumab demonstrated rapid and clinically meaningful benefit across a number of important disease activity parameters,” said lead study investigator Gerd Burmester Professor of Medicine, Department of Rheumatology and Clinical Immunology, Charité University Hospital, Free University and Humboldt University of Berlin, Germany. “These data support further development of mavrilimumab as a potential new therapy with a unique mechanism of action for RA patients who are not responding to currently available therapies.”
About Rheumatoid Arthritis (RA)
Rheumatoid arthritis is a painful, systemic, chronic inflammatory autoimmune disease which causes damage to the joints and vital organs. The disease affects approximately one in 100 people worldwide. If not adequately treated, RA is a major cause of disability leading to diminished work capacity and is associated with reduced life expectancy.
The American College of Rheumatology (ACR) response represents a percentage improvement in symptoms. To achieve an ACR20 score, a person with RA must have at least 20 percent fewer tender joints and at least 20 percent fewer swollen joints. In addition the patient must also have a 20 percent improvement in at least three of the following five areas: 1) the patients overall (global) assessment of their RA 2) the patient assessment of their pain 3) the patients assessment of their physical functioning 4) the physician’s global assessment of their patients RA, and 5) the results of a C-reactive protein and erythrocyte sedimentation rate blood test as key indicators of inflammation.
The Disease Activity Score (DAS) represents an assessment of disease symptoms. The DAS score consists of a numerical assessment of a set of 28 joints for swelling and tenderness, plus the patients overall (global) assessment of their RA and the results of a C-reactive protein and erythrocyte sedimentation rate blood test as key indicators of inflammation.
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.
MedImmune is the worldwide biologics research and development arm of AstraZeneca, a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialization of small molecule and biologic prescription medicines. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centers. For more information, please visit www.medimmune.com.
Susannah Budington, MedImmune
Tracy Rossin, MedImmune