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|Array BioPharma Announces Top-Line Results from Rheumatoid Arthritis Phase 2 Trial|
Overall, the placebo response rates in this study were higher than
expected for this patient population and showed regional differences,
with patients in
“This is the first clinical trial evaluating the modulation of the MEK
pathway for the treatment of chronic inflammatory disease,” said
Array will host a conference call on
The table below shows the ACR20 response rates at 12 weeks evaluated overall and by region in the efficacy evaluable population using last observation carried forward method.
ACR20 Response Rates at 12 weeks – Overall and by Region
*Global P value compares all four treatment arms.
Consistent with earlier studies of up to 28 days with ARRY-162, the most common drug-related adverse events (AEs) observed in the study were skin-related (e.g., rash, dermatitis) and diarrhea. The incidence of these findings were most common in the 20 mg BID and 40 mg QD dose groups, and were generally mild-to-moderate in intensity. There were no drug-related serious adverse events. The table below shows the most frequently reported drug-related adverse events in the safety population.
Most Commonly Reported Drug-Related Adverse Events
Drug-related as assessed by investigators, blinded to treatment.
About Rheumatoid Arthritis
Rheumatoid Arthritis (RA) is a debilitating autoimmune disease that affects more than two million Americans, and as many as 1% of the global population, and hinders the daily activities of sufferers. The damage that occurs in RA is a result of the immune system attacking joint tissue, causing painful chronic inflammation, often resulting in irreversible destruction of cartilage, tendons and bones. Common RA symptoms include inflammation of the joints, swelling, fatigue, stiffness and pain. Additionally, since RA is a systemic disease, it can have effects in other tissues such as the lungs and eyes.
ARRY-162 Phase 2 RA Trial Design
This was a Phase 2, randomized, double-blind, placebo-controlled,
12-week, parallel treatment trial of ARRY-162 in patients with active RA
on stable doses of methotrexate. Patients entering the study had an
inadequate response to methotrexate (≥6 swollen and ≥6 tender joints
with C-reactive protein ≥1 mg/dL at screening) and had been on a stable
dose of methotrexate for at least 6 weeks prior to study entry. Prior
therapy with biologics was not allowed. 201 patients were enrolled in
this study. Patients were randomized 1:1:1:1 to one of three dosing
regimens of ARRY-162 (10 mg BID, 20 mg BID, 40 mg QD) or placebo. The
study enrolled 100 patients in
About ARRY-162 in Inflammatory Diseases
ARRY-162, an orally active MEK inhibitor, has shown significant efficacy and is well tolerated in preclinical models of human arthritis and other inflammatory diseases. In preclinical combination studies with standard of care RA treatments, including methotrexate, dexamethasone, ibuprofen, and etanercept, ARRY-162 was well tolerated and demonstrated at least additive efficacy, even with the maximally efficacious dose of etanercept. ARRY-162 was well-tolerated in preclinical studies for up to 9 months of daily dosing. Phase 1 clinical trials with ARRY-162 have demonstrated selective and dose-dependant inhibition of IL-1, IL-6 and TNF with convenient oral dosing, as well as good tolerability when used in combination with methotrexate.
About ARRY-162 in Cancer
Array believes ARRY-162 is particularly well-suited for use in cancer treatment and has advantages over other MEK inhibitors currently in development, including greater potency, and improved safety and pharmacokinetics. ARRY-162 has been administered to more than 230 patients/healthy subjects in clinical trials for either safety assessment or the treatment of inflammatory disease. The drug has been well-tolerated and demonstrated significant pharmacodynamic responses in the completed trials. In addition, the Company has completed long-term preclinical regulated safety studies and has identified a commercially viable synthetic process and oral formulation for ARRY-162.
MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which mediates production of key proinflammatory cytokines, including TNFα, IL-1β and IL-6, as well as cellular proliferation and survival. It also has a role in pathogenic bone remodeling through direct effects on osteoclasts, the cells responsible for bone resorption. MEK inhibition therefore has the potential to be a novel and safe approach to treating chronic, progressive inflammatory diseases because of its observed anti-inflammatory and bone anti-resorptive effects. In addition, MEK is frequently activated in cancer, in particular in tumors that have mutations in the RAS and RAF oncogenes. Preclinical data show that MEK inhibitors are additive or synergistic in combination with other agents. In particular, the PI-3K/AKT/mTOR pathway interacts with the RAS/RAF/MEK/ERK pathway in response to growth factor signaling. Simultaneous inhibition of both these pathways has significantly greater preclinical anti-tumor activity compared to inhibition of either pathway alone. Because these pathways are commonly activated in many tumors, we believe that dual MEK and PI3K/AKT/mTOR inhibition could have broad anti-tumor activity.
A replay of the call will be available as a webcast on the Investor Relations section of Array’s website www.arraybiopharma.com.
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements about our future plans for advancing development of
ARRY-162 and the potential for the results of ongoing preclinical and
clinical trials to support regulatory approval or the marketing success
of a drug candidate. These statements involve significant risks and
uncertainties, including those discussed in our most recent annual
report filed on form 10-K, in our quarterly reports filed on Form 10-Q,
and in other reports filed by Array with the
Array BioPharma Inc.