Abbott Receives FDA Approval for HUMIRA® (Adalimumab) for Polyarticular Juvenile Idiopathic Arthritis

HUMIRA Is the First Biologic Treatment Approved in Nine Years for Children Suffering from This Potentially Debilitating Autoimmune Disease

Abbott Park, Illinois — Abbott announced today it has received U.S. Food and Drug Administration (FDA) approval to market HUMIRA® (adalimumab) as a treatment to reduce signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients four years of age and older.In the U.S., JIA is commonly referred to as juvenile rheumatoid arthritis (JRA).The approval is based on safety and efficacy results from a clinical study of JIA patients four to 17 years of age. HUMIRA is the first biologic treatment to receive FDA approval for this condition since 1999, and the first to be administered by injection in these patients once every two weeks.

“The pain and inflammation caused by JIA can be debilitating for some children, making it hard for them to run, jump, play or participate in other activities with children their age,” said Daniel J. Lovell, M.D., M.P.H., associate director, Division of Rheumatology, Cincinnati Children’s HospitalMedicalCenter, Cincinnati.“HUMIRA is an important new treatment that gives physicians and families another option that can ease the symptoms of polyarticular JIA.”

JIA is the most common chronic rheumatic disease in children with onset before age 16. Typical symptoms include stiffness when awakening, limping, and joint swelling. Any joint can be affected and inflammation may limit the mobility of the affected joints. While it was once believed that most children eventually outgrow JIA, it is now known that between 25 and 70 percent of children with JIA will still have active disease into adulthood.

“The symptoms of JIA can make it difficult for children to experience many of the simple joys of childhood,” said John Hardin, M.D., chief scientific officer, Arthritis Foundation. “The Arthritis Foundation welcomes the approval of new therapies that expand effective treatment options for doctors and families, helping children and adolescents to keep their symptoms under control.”

JIA is the sixth disease indication for which HUMIRA has received approval since 2002.
HUMIRA JIA Clinical Study

The approval is based on the results of a 48-week study and a subsequent open-label extension evaluating the efficacy and safety of HUMIRA. In the 48-week study, fewer children treated with HUMIRA experienced disease flare compared to placebo. Overall, children on HUMIRA experienced improvements in their disease symptoms.

The 48-week Phase III study included 171 children (four to 17 years of age) with polyarticular JIA, a form of arthritis affecting five or more joints, usually the same joints on both sides of the body.

In the first part of this study, two groups of patients – those taking methotrexate (MTX) and those not taking MTX – received open-label HUMIRA (up to a maximum of 40 mg) every other week for 16 weeks. Patient responses were measured using the American College of Rheumatology Pediatric (ACR Pedi) 30 score, which represents a 30 percent or greater improvement in JIA signs and symptoms, such as the number of swollen joints with loss of motion, assessment of pain and level of disability. Children who showed a positive clinical response (n=133) entered the second part of the study and were randomized to receive HUMIRA or placebo for an additional 32 weeks or until disease flare. A flare was defined as a worsening of 30 percent or more in at least three of the six ACR Pedi response variables, a minimum of two active joints, and no more than one indicator improving by 30 percent.

In the second part of this study, significantly fewer children receiving HUMIRA demonstrated disease flare compared to children on placebo, both without MTX (43 percent vs. 71 percent) and with MTX (37 percent vs. 65 percent). Additionally, more patients treated with HUMIRA continued to show ACR Pedi 30/50/70 responses at week 48 compared to placebo.

At the conclusion of the 48-week study or at the time of disease flare during the double-blind phase, patients could enter the open-label extension period. Efficacy and safety were assessed at routine intervals throughout the study. ACR Pedi responses were maintained for up to two years in patients who received HUMIRA throughout the study.

Upon initiation of treatment with HUMIRA, the most common adverse reactions that occurred were injection site pain and injection site reaction (19 percent and 16 percent, respectively).

“The approval of HUMIRA provides an excellent option in the treatment of JIA,” said Eugene Sun, M.D., vice president, Global Pharmaceutical Clinical Development, Abbott. “In addition to its efficacy in reducing the signs and symptoms of polyarticular JIA, we believe that children and their caretakers will appreciate the benefit of convenient every-other-week dosing that HUMIRA offers.”

HUMIRA is administered at home via an injection every other week. JIA patients who weigh 30 kilograms (66 pounds) or more will use the same 40 mg HUMIRA Pen or pre-filled syringe currently used by adult HUMIRA patients. Children who weigh at least 15 kilograms (33 pounds), but less than 30 kilograms, will receive HUMIRA via a 20 mg pre-filled syringe manufactured exclusively for JIA patients.
Important Safety

Serious infections, sepsis, tuberculosis (TB) and opportunistic infections, including fatalities, have been reported with the use of TNF-blocking agents, including HUMIRA. Many of these serious infections have occurred in patients also taking other immunosuppressive agents that in addition to their underlying disease could predispose them to infections. Infections have also been reported in patients receiving HUMIRA alone. Treatment with HUMIRA should not be initiated in patients with active infections. TNF-blocking agents, including HUMIRA, have been associated with reactivation of hepatitis B (HBV) in patients who are chronic carriers of this virus. Some cases have been fatal. Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating HUMIRA. The combination of HUMIRA and anakinra is not recommended and patients using HUMIRA should not receive live vaccines.

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 three-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. 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.

Worsening congestive heart failure (CHF) has been observed with TNF-blocking agents, including HUMIRA, and new onset CHF has been reported with TNF-blocking agents. Treatment with HUMIRA may result in the formation of autoantibodies and rarely, in development of a lupus-like syndrome.

In the placebo-controlled clinical studies of adult patients with rheumatoid arthritis, the most frequent adverse reactions vs. placebo were injection site reactions (20 percent vs. 14 percent), upper respiratory infection (17 percent vs. 13 percent), injection site pain (12 percent vs. 12 percent), headache (12 percent vs. 8 percent), rash (12 percent vs. 6 percent) and sinusitis (11 percent vs. 9 percent). Discontinuations due to adverse events were 7 percent for HUMIRA and 4 percent for placebo.

In HUMIRA clinical trials for ankylosing spondylitis, psoriatic arthritis, Crohn’s disease and plaque psoriasis, the safety profile for adult patients treated with HUMIRA was similar to the safety profile seen in adult patients with rheumatoid arthritis. In the placebo-controlled clinical trials in plaque psoriasis, the incidence of arthralgia was 3 percent in HUMIRA-treated patients versus 1 percent in controls.

In general, adverse reactions in pediatric patients were similar in frequency and type to those seen in adult patients. Severe adverse reactions reported in the clinical trial in JIA included neutropenia, streptococcal pharyngitis, increased aminotransferases, herpes zoster, myositis, metrorrhagia and appendicitis. Serious infections were observed in 4 percent of patients within approximately two years of initiation of treatment with HUMIRA and included cases of herpes simplex, pneumonia, urinary tract infection, pharyngitis, and herpes zoster. Safety of HUMIRA in pediatric patients for uses other than juvenile idiopathic arthritis have not been established.

As with any treatment program, the benefits and risks of HUMIRA should be carefully considered before initiating therapy.