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:
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EARTH EXPLORER I Phase IIb study met co-primary endpoints at all
mavrilimumab doses:
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American College of Rheumatology 20 percent improvement criteria
(ACR20) at week 24
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Mean change from baseline in the Disease Activity Score 28-joint
Disease Activity Score based on C-reactive protein (DAS28-CRP) at
week 12
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All secondary endpoints including ACR50, ACR70 response and DAS28
remission score achieved statistical significance for the high dose of
150 mg.
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Mavrilimumab produced a rapid and sustained improvement in multiple
symptoms of rheumatoid arthritis after one week and one dose.
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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.
About Mavrilimumab
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.
About MedImmune
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.
Copyright Business Wire 2014