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Humira (adalimumab) Receives FDA Approval for First-Line Treatment of Moderate to Severe Rheumatoid Arthritis

Forty-Three Percent of Study Patients on Combination Therapy Achieved Clinical Remission at Year 1; Forty-Nine Percent at Year 2

ABBOTT PARK, IL -- October 4, 2005 -- Abbott announced today that it received U.S. Food and Drug Administration (FDA) approval to market Humira(R) (adalimumab) for first-line treatment of recent onset moderate to severe rheumatoid arthritis (RA). The approval offers RA patients an important therapeutic option early in the course of their disease, when there is a critical window of opportunity to intervene before the potential crippling effects of joint destruction and long-term disability set in. In 2002, Humira was approved to treat patients with moderately to severely active RA, who have had insufficient response to one or more disease-modifying anti-rheumatic drugs (DMARDs).

Humira Offers Proven Benefit in Early RA
The approval for the expanded indication is based on clinical and radiographic data from the two-year PREMIER study of 799 methotrexate (MTX)-naive patients with active recent onset moderate to severe RA (defined as disease of less than three years duration). On average, patients had less than nine months of disease duration from the time of diagnosis.

The trial compared three arms, Humira monotherapy, MTX monotherapy, and the two drugs combined in treating this patient population. The study showed Humira in combination with MTX was superior to MTX alone on several efficacy endpoints, including the two primary endpoints -- inhibition of joint damage and improvement in signs and symptoms at 1 year -- and a secondary endpoint, achievement of clinical remission measure of DAS28<2.6 at 1 year. The Disease Activity Score (DAS) measures disease activity responses in RA by assessing tender and swollen joint count, general health status and an inflammatory marker.

"Mounting evidence suggests that early and aggressive treatment of moderate to severe RA can achieve favorable outcomes, since joint damage can occur quickly, even in the first year," said Arthur Kavanaugh, MD, UCSD Center for Innovative Therapy, La Jolla, California, and PREMIER investigator. "Humira (adalimumab) has been shown to slow the progression of RA when initiated in patients early in their treatment. For many patients, this means reduction in signs and symptoms, but more importantly, significant inhibition of joint damage."

Inhibition of Joint Damage in Early RA
The PREMIER study showed patients taking Humira in combination with MTX experienced significantly less joint damage as measured by the change in modified Total Sharp Score, or mTSS, than those on MTX alone. Modified Total Sharp Score assesses bone erosion and joint space narrowing on X-rays. A smaller change in mTSS reflects less progression of joint damage. Also, approximately twice as many patients on the Humira-MTX regimen experienced no further joint destruction compared to those on MTX alone (61% vs. 34%) after 2 years. No joint destruction was defined as less than or equal to 0.5 units change from baseline in mTSS.

After 1 year, patients on MTX alone had four times the disease progression as those in the Humira-MTX regimen, with a mean change in mTSS of 5.7 vs. 1.3 respectively, and after 2 years, patients on MTX alone had five times more disease progression than those on the Humira-MTX regimen, with a mean change in mTSS of 10.4 vs. 1.9 respectively.

Improvement in RA Signs and Symptoms
In this trial, Humira in combination with MTX significantly improved the signs and symptoms of RA. After 1 year, 62% of patients on the Humira-MTX regimen achieved ACR50 (a 50% or greater improvement in signs and symptoms of RA) compared to 46% on MTX alone and 41% on Humira alone. After 2 years, 59% of patients on the Humira-MTX regimen achieved ACR50 compared to 43% on MTX alone and 37% on Humira alone. PREMIER is the first RA trial to measure ACR50 as a primary endpoint. American College of Rheumatology (ACR) scores measure the percentage of improvement in tender and swollen joint count and several other clinical measures.

Major Clinical Response
Forty-three percent of patients on the Humira-MTX regimen achieved a measure of clinical remission as defined by DAS28<2.6 at 1 year vs. 21% of patients on MTX only, and nearly one in two patients on the combination therapy achieved clinical remission at 2 years compared with one in four patients on MTX alone (49% vs. 25%). Additionally, almost half of patients on the Humira-MTX regimen achieved major clinical response, defined as achieving and maintaining an ACR70 response for six or more continuous months, compared to MTX alone (49% vs. 28%). Also, 27% of patients on the Humira-MTX regimen achieved ACR90 at 2 years, a 90% or greater improvement in signs and symptoms, compared to 13% on MTX alone.

"Humira has been an important treatment choice for thousands of patients with moderate to severe RA, and we're pleased that it is now available to patients earlier in their disease, offering the potential to improve outcomes," said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development at Abbott. "The PREMIER study demonstrates treatment of RA with Humira can inhibit progression of joint destruction at an earlier stage of the disease."

In this trial, all treatment arms had a comparable overall rate of adverse events. Among patients taking Humira, the most common adverse events were nasopharyngitis, headache, nausea, diarrhea, joint pain, and pharyngitis.

In December 2004, Abbott simultaneously submitted applications to the FDA and the European Medicines Agency seeking approval to market Humira to treat early RA and psoriatic arthritis. Humira received European approval for early severe RA and psoriatic arthritis on Aug. 8, 2005.

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 the 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, potentially resulting in destruction of the joints' interior and the surrounding bone.

Important Safety Information
Cases of tuberculosis (TB) have been observed in patients receiving Humira. Serious infections and sepsis, including fatalities, have been reported with the use of TNF-blocking agents, including Humira. Many of these infections occurred in patients also taking other immunosuppressive agents that in addition to their underlying disease could predispose them to infections. Treatment with Humira should not be initiated in patients with active infections. The combination of Humira and anakinra is not recommended.

TNF-blocking agents, including Humira, have been associated in rare cases with demyelinating disease and severe allergic reactions. Infrequent reports of serious blood disorders have been reported with TNF-blocking agents. More cases of malignancies have been observed among patients receiving TNF blockers, including Humira, compared to control patients in clinical trials. These malignancies, other than lymphoma and non-melanoma skin cancer, were similar in type and number to what would be expected in the general population. There was an approximately four fold higher rate of lymphoma in combined controlled and uncontrolled open label portions of Humira clinical trials. The potential role of TNF-blocking therapy in the development of malignancies is not known.

The most frequent adverse events seen in the placebo-controlled clinical trials in rheumatoid arthritis (Humira vs. placebo) were injection site reactions (20% vs. 14%), upper respiratory infection (17% vs. 13%), injection site pain (12% vs. 12%), headache (12% vs. 8%), rash (12% vs. 6%) and sinusitis (11% vs. 9%). Discontinuations due to adverse events were 7% for Humira and 4% for placebo. As with any treatment program, the benefits and risks of Humira should be carefully considered before initiating therapy.

The safety profile for patients with psoriatic arthritis treated with Humira in the clinical trials has been similar to the safety profile seen in patients with RA.

About Humira
Humira is the only fully human monoclonal antibody approved by the FDA for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active RA. Humira can be used alone or in combination with MTX or other DMARDs. Humira offers convenient every-other-week dosing by subcutaneous injection (shot beneath the skin) via a specially designed pre-filled syringe.

Clinical trials are currently underway evaluating the potential of Humira in other autoimmune diseases.


SOURCE: Abbott

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