[ D2E7/RA ]
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, Sweden, June 14 /PRNewswire/ -- Results from Phase III and
ongoing clinical trials of Abbott Laboratories' investigational fully human
monoclonal antibody, D2E7 (adalimumab, ?-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
Michael 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
Paul 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, 2002 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, 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, 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.
Abbott's news releases and other information are available on the
company's Web site at abbott.com.
SOURCE Abbott Laboratories
Web Site: abbott.com
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