D2E7 (adalimumab) is being developed as the first fully human monoclonal antibod

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FIRST PHASE III DATA FOR ABBOTT LABORATORIES' D2E7 (ADALIMUMAB)

SUPPORT PROMISE IN RHEUMATOID ARTHRITIS (RA)

—RESULTS PRESENTED AT EUROPEAN RHEUMATOLOGY MEETING SUGGEST SAFETY

AND DURABILITY OF RESPONSE IN RA—

Stockholm, June 14, 2002 — Results from Phase III and ongoing

clinical trials of Abbott Laboratories' investigational fully human

monoclonal antibody, D2E7 (adalimumab, â-da-lim-yoo-mab), show a

statistically significant reduction in the signs and symptoms of

rheumatoid arthritis (RA). The studies also show rapid and sustained

positive clinical responses with D2E7 when administered as a

monotherapy or in combination with methotrexate (MTX) or other

multiple disease modifying anti-rheumatic drugs (DMARDs). Therapy

with multiple treatments is common in clinical practice. The data

from several studies, presented today at the European League Against

Rheumatism (EULAR) annual meeting, contribute to a better

understanding of the safety and efficacy profiles of D2E7 and are

part of the global regulatory submissions to support marketing

approval of the drug.

" RA is a progressive disease that can be very debilitating for

patients, which is why the research we are conducting with D2E7 is so

exciting, " said Schiff, M.D., clinical professor of medicine,

Rheumatology Division, University of Colorado School of Medicine and

a lead investigator for D2E7 clinical trials. " The Phase III data for

D2E7 offer patients hope for a potential new option that has

demonstrated favorable clinical results with convenient dosing and

administration. "

Phase III STAR Trial Results

Results from the Phase III STAR (Safety Trial of Adalimumab in

Rheumatoid Arthritis) trial, one of the largest, controlled safety

studies in RA, show that after 24 weeks of therapy, there were no

statistically significant differences in rates of adverse events,

serious adverse events, infections, or serious infections between

placebo or D2E7 when added to patients' pre-existing anti-rheumatic

therapy. The trial included 636 patients and was designed to assess

safety as a primary endpoint with a protocol that represented common

clinical practice, in which it is common for physicians to prescribe

a combination of DMARDs for patients with RA.

Patients in the study were taking up to four DMARDs when they were

randomized to receive subcutaneous doses of either placebo or 40 mg

of D2E7, every-other-week, in addition to their current DMARDs. The

only adverse events that differed significantly between D2E7 and

placebo were injection site reactions, rash and back pain.

Effectiveness of D2E7 was also measured in the STAR trial 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 counts and other

relevant clinical measures. Overall, significantly more patients

receiving D2E7 experienced an improvement of symptoms with ACR 20,

ACR 50 and ACR 70 responses, compared with patients receiving placebo

(55 percent vs. 36 percent, 30 percent vs. 11 percent, and 15 percent

vs. 3 percent, respectively). In this study, D2E7 demonstrated

positive clinical results and safety in a diverse group of patients

with RA, many of who required multiple anti-rheumatic therapies.

" Based on results from our extensive study of D2E7 to date, including

one of the largest safety trials in RA, we are excited about the

potential D2E7 may have in RA, " said Jeff Leiden, M.D., Ph.D.,

president and chief operating officer, Pharmaceutical Products Group,

and chief scientific officer, Abbott Laboratories. " Because RA is an

auto-immune disease, patients are more likely to have infections, and

it is critically important for us to understand the safety profile of

D2E7. Based on the number of patients who have taken D2E7 and the

number of studies we've completed, we are confident in the safety and

efficacy profiles, and the convenience D2E7 may offer patients with

RA. "

Ongoing Results from Phase II ARMADA Trial

One-year results from the Phase II ARMADA (Anti-TNF Research Study

Program of the Monoclonal Antibody D2E7 in Patients with Rheumatoid

Arthritis) trial show that 89 percent of patients (241/271) who

entered the trial elected to remain on D2E7 therapy in combination

with MTX for more than one year.

In addition, after 12 months of therapy with D2E7 and MTX, more than

one in four patients treated with D2E7 (25.3 percent) achieved the

ACR 70 response (the clinical measure closest to remission of RA

symptoms). ACR 20 and ACR 50 responses were achieved by 70 percent

and 48 percent of patients receiving D2E7, respectively.

The ARMADA trial was a 24-week, double-blind, placebo-controlled

study that included 271 patients with active RA despite recurrent

treatment with MTX. All patients had failed between one and four

DMARDs prior to MTX therapy. The 24-week phase was followed by a six-

month, open-label extension in which all patients received the 40 mg

dose of D2E7 subcutaneously every other week. In this trial, the

frequency and type of adverse events were similar during the blinded

and open-label phases.

D2E7 Studied in Patients with Severe RA as Monotherapy

In another Phase III trial, D2E7 was studied in 544 patients with

long-standing RA who had tried and failed treatment with an average

of 3.7 other DMARDs. Of the patients in the trial, 72 percent had

failed treatment with three or more DMARDs, and 90 percent had failed

treatment with MTX. The patients involved in the study also had

advanced disease as determined by an average duration of RA of 11

years, an average tender joint count (TJC) of 34, and an average

swollen joint count (SJC) of 20. The TJC and SJC are determined by

examining the number of joints affected by the disease.

Responses to D2E7 were rapid, with many patients attaining ACR 20

response by week two (36 percent of patients), ACR 50 by week eight

(23 percent of patients), and ACR 70 by week 12 (11 percent of

patients); these results were sustained throughout the 26-week study.

In addition, the most significant response of ACR 70 was achieved by

12 to 18 percent of patients receiving 40 mg of D2E7 every other week

or weekly, compared to only 1.8 percent of those receiving placebo

(p<0.05) at week 26. Overall, D2E7 used as monotherapy in patients

with advanced RA demonstrated statistically significant positive

clinical results at all doses tested compared to placebo.

This Phase III study was designed to assess the efficacy and safety

of D2E7 in patients who were randomized to receive D2E7 at 20 mg or

40 mg doses every other week or weekly, or placebo. The most common

adverse events in patients receiving D2E7 compared to placebo were

injection site reactions (10.6 percent vs. 0.9 percent), rash (15.7

percent vs. 5.5 percent), and headache (20 percent vs. 10 percent).

" We are excited about the results we continue to see with D2E7, " said

Emery, M.D., professor of rheumatology, Rheumatology and

Rehabilitation Research Unit, University Hospital Leeds,

England. " Based on all of the clinical studies to date, we have shown

that D2E7 can have a positive impact on the signs and symptoms of RA.

Longer-term studies are helping us understand the durability of those

responses. "

Long-Term Studies up to 2.5 Years

Data from two open-label extension trials were also presented, which

included patients remaining on D2E7 therapy for as long as 2.5 years.

In the first extension study, 98 percent (53/54) of patients

originally included in a Phase I trial with D2E7 and MTX chose to

enter a long-term, open-label trial that continued out to 2.5 years.

Forty-three patients (80 percent) completed the 2.5-year study

period. ACR responses with D2E7 were maintained, and in some cases,

improved after 2.5 years of therapy: ACR 50 response was achieved by

28 percent of patients (15/54) taking D2E7 at 12 months, and by 35

percent of patients (19/54) at 30 months. Swollen joint count (SJC)

was also measured during the study. After 2.5 years of D2E7 therapy,

the average SJC was 5.8, compared to previous results of 8.2 after 12

months, and 19.8 at the start of the study. Throughout the 2.5-year

study, the rate of adverse events did not change.

In a separate Phase II, open-label extension study, efficacy and

safety of D2E7 out to two years of therapy was assessed in 229

patients who had long-standing RA and had failed at least one DMARD.

More than 75 percent achieved an ACR 20 response, more than half (52

percent) achieved an ACR 50 response, and nearly one in four patients

(24 percent) achieved an ACR 70 response at 24 months. These results

point to a sustained response out to 24 months from those achieved

after 12 months of therapy. Increases were seen in the ACR 50

response (up from 46 percent of patients) and the ACR 70 response (up

from 21 percent of patients) at 24 months.

About D2E7

Abbott Laboratories announced on April 9 that it had submitted

regulatory applications to the U.S. Food and Drug Administration

(FDA) and the European Agency for the Evaluation of Medicinal

Products (EMEA). The company also confirms that the FDA has recently

accepted the submission for review, and the Committee for Proprietary

Medicinal Products (CPMP) accepted the submission for review in April.

The regulatory submissions in the United States and Europe are based

on data from 23 clinical trials involving more than 2,300 RA patients

in North America, Europe and Australia, making D2E7 the most-studied

anti-TNF agent at the time of submission for regulatory approvals.

D2E7 (adalimumab) is being developed as the first fully human

monoclonal antibody for RA. D2E7 works by specifically blocking the

activity of tumor necrosis factor alpha (TNF-alpha), which plays a

central role in the inflammation of autoimmune diseases such as RA.

D2E7 was discovered through a broad scientific collaboration between

Abbott (then BASF Pharma) and Cambridge Antibody Technology (CAT). As

part of the collaboration, Abbott had the right to select several

target antigens for which a joint CAT/Abbott research team would

discover human antibody therapeutics. D2E7 was isolated and optimized

by Abbott and CAT as part of this collaboration. Abbott owns

exclusive worldwide rights to D2E7, including responsibility for

manufacturing, clinical development, and sales and marketing. Abbott

will book all revenues for D2E7, and CAT will receive a royalty fee

based on D2E7 sales.

About RA

More than 5 million people worldwide suffer from RA, a chronic

autoimmune disease that causes pain, swelling and stiffness in the

joints of hands, feet and wrists, and often leads to the destruction

of joints. Unlike osteoarthritis, the most common form of arthritis,

RA is an autoimmune disease where joints are inflamed, resulting in

eventual destruction of the joint's interior and the surrounding

bone. The long-term prognosis for patients with RA is poor, and as a

result, many patients face increased disability and premature death.

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, Massachusetts, 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, broad-based 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.