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News Release

Abbott Laboratories' Investigational Fully Human Anti-TNF therapy, D2E7 (Adalimumab), Shows Promise in Reducing the Signs and Symptoms of Rheumatoid Arthritis

November 12, 2001 at 10:01 AM EST
SAN FRANCISCO, Nov 12, 2001 /PRNewswire via COMTEX/ -- Results from the Phase II clinical trial called ARMADA (Anti-TNF Research Study Program of the Monoclonal Antibody D2E7 in Patients with Rheumatoid Arthritis), suggest that Abbott Laboratories' D2E7 (adalimumab), in development for rheumatoid arthritis (RA), reduces the signs and symptoms of moderate to severe rheumatoid arthritis. D2E7 is the first fully human monoclonal antibody in development. D2E7 is an investigational agent designed to block the activity of tumor necrosis factor alpha (TNF-alpha), which contributes to the inflammation in autoimmune diseases such as RA.

"In this study, D2E7 showed promise in reducing the signs and symptoms of rheumatoid arthritis," said Edward Keystone, M.D., director, Center for Advanced Therapeutics, University of Toronto, Canada, and lead investigator in the D2E7 studies. "Developing potential new treatment options for RA, a debilitating joint disease, is critical."

D2E7 Phase II Study Data

Two hundred seventy-one (271) patients were enrolled in the ARMADA Trial, a 24-week, double-blind, placebo-controlled Phase II study. Participants had active RA despite current treatment with methotrexate (MTX), a disease modifying anti-rheumatic drug (DMARD). All patients had failed between one and four DMARDs prior to MTX therapy. All patients continued on MTX and were randomized to receive either D2E7 (n=209) at 20, 40 or 80 mg doses or placebo (n=62) administered by subcutaneous injection every other week for 24 weeks.

Results were measured using American College of Rheumatology (ACR) criteria. ACR 20, ACR 50 and ACR 70 represent the percentage of improvement (20 percent, 50 percent, and 70 percent) in tender and swollen joint count and other relevant clinical measures such as pain scale and physician assessment of disease activity.

Among patients receiving 40 mg of D2E7 every other week, 65.7 percent achieved ACR 20 versus 14.5 percent in the placebo group, 53.7 percent achieved ACR 50 versus 8.1 percent in the placebo group, and 26.9 percent achieved ACR 70 versus 4.8 percent in the placebo group (p<(or equal to) 0.02 for all D2E7 doses versus placebo) at 24 weeks. Results from the trial show patients in the D2E7 treatment group experienced statistically significant improvement compared with placebo in reducing the signs and symptoms of RA at all doses. Injection site reactions occurred more frequently in D2E7-treated patients versus placebo (15.2 percent vs. 3.2 percent); adverse events were generally similar in the treatment groups. Eighteen patients withdrew from the study (9 from D2E7 and 9 from placebo).

D2E7 Impact on Potential Indicators of Disease Progression

Additionally, researchers examined the effect of D2E7 on two enzymes associated with joint destruction, metalloproteinase-1 and metalloproteinase-3 (MMP-1 and MMP-3), in the 271 patients through week 24 of the ARMADA Trial. MMP-1 and MMP-3 are enzymes that cause destruction of cartilage and bone. Patients received either placebo or D2E7 every other week in combination with methotrexate; MMP-1 and MMP-3 levels were measured at both 12 and 24 weeks.

At 24 weeks, patients in the D2E7 treatment group had a 23.3 percent decrease in MMP-1 and a 26.6 percent decrease in MMP-3, versus an increase of 10.4 percent in MMP-1 and an increase of 17.8 percent in MMP-3 in the placebo group (p<0.01).

    ARMADA Results
Placebo Placebo D2E7* D2E7*


12 weeks 24 weeks 12 weeks 24 weeks

ACR20 (% of patients) 22.6 14.5 64.1** 62.2**

ACR50 (% of patients) 9.7 8.1 28.7** 43.5**

ACR70 (% of patients) 4.8 4.8 11.0** 19.1**

MMP-1 (% change) +11.9 +10.4 -17.9** -23.3**

MMP-3 (% change) +6.2 +17.8 -29.5** -26.6**

*Three doses of D2E7 (20 mg, 40 mg, 80 mg every other week) combined and overall results shown here. ** = p< 0.01 versus placebo.

"These findings suggest that D2E7, in addition to improving the signs and symptoms of RA, also decreases the levels of serum MMP-1 and MMP-3, which may potentially be indicators of erosion and destruction of the joints," said Steven Fischkoff, M.D, clinical director of global D2E7 development, Abbott Laboratories.

"Abbott continues to be excited about the performance of D2E7 in clinical studies," said Jeff Leiden, M.D, Ph.D., chief scientific officer and executive vice president, pharmaceuticals, Abbott Laboratories. "Phase III studies are complete and results are being analyzed. We remain on target to make our regulatory submission in the U.S. and Europe during the second quarter of 2002 and throughout the rest of the world thereafter."

Abbott's Commitment to Immunology

Abbott Laboratories is committed to the discovery and development of innovative treatments for immunologic diseases. Founded in 1989, the Abbott Bioresearch Center in Worcester, Mass., is a world-class discovery and basic research facility committed to finding new treatments for autoimmune diseases. Abbott Bioresearch Center employs leading-edge technologies, discovery and manufacturing processes, including proprietary phage antibody display technology, and mammalian cell expression systems to produce fully human monoclonal antibodies.

Abbott Laboratories is a global, diversified health care company devoted to the discovery, development, manufacture and marketing of pharmaceuticals, nutritionals, and medical products, including devices and diagnostics. The company employs approximately 70,000 people and markets its products in more than 130 countries.

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