Celgene Corporation has announced that the U.S. Food and Drug Administration (FDA) has approved OTEZLA® (apremilast), the Company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), for the treatment of adult patients with active psoriatic arthritis. A chronic disorder, psoriatic arthritis is characterized by pain, stiffness, swelling and tenderness of the joints, inflammation of specific ligaments and tendons, and a decrease in physical functioning. OTEZLA is the only FDA-approved oral treatment for psoriatic arthritis.
"The approval of oral OTEZLA is significant for patients living with psoriatic arthritis, which is a debilitating, painful disease that has a significant effect on a patient's day-to-day activities," said Dr. Alvin Wells, M.D., Ph.D., Director, Rheumatology and Immunotherapy Center, Franklin, WI, U.S. "OTEZLA offers physicians and patients a meaningful new treatment option, with the potential to benefit psoriatic arthritis patients irrespective of prior treatment."
"OTEZLA works differently from other therapies approved for psoriatic arthritis through the intracellular inhibition of PDE4," said Philip Mease, MD, Director of the Rheumatology Clinical Research Division of Swedish Medical Center and Clinical Professor, University of Washington. "The approval of an oral therapy with a novel mechanism of action for patients with psoriatic arthritis offers a different approach to patient care."
The approval was based on safety and efficacy results from three multi-center, randomized, double-blind, placebo-controlled trials - PALACE 1, 2 and 3 - conducted in adult patients with active psoriatic arthritis who were inadequately controlled by disease-modifying anti-rheumatic drugs (DMARDs) and/or biologics. More than 75 percent of patients were previously treated with DMARDs only and 22 percent of patients were previously treated with biologics.
OTEZLA treatment with or without (±) concomitant DMARDs, compared with placebo ± concomitant DMARDs, resulted in greater improvement in the signs and symptoms of psoriatic arthritis, as demonstrated by the proportion of patients with an ACR 20 response at week 16. In PALACE-1, 38 percent of patients treated with OTEZLA® (apremilast) 30 mg twice daily achieved an ACR 20 response at week 16 versus 19 percent of patients on placebo. Consistent results were observed in PALACE-2 and PALACE-3. Improvement in ACR 50 and ACR 70 responses were observed at week 16 across the three studies.
A characteristic of psoriatic arthritis is tenderness and swelling in and around the joints. At week 16, patients treated with OTEZLA achieved a reduction in tender and swollen joint counts compared with placebo. OTEZLA treatment resulted in improvement for each of the seven ACR components measured, compared with placebo, at week 16. Improvements were also seen in disease-related physical functioning.
Treatment with OTEZLA resulted in improvement in dactylitis (inflammation of fingers and toes) and enthesitis (inflammation at sites where tendons or ligaments insert into bone) in patients with these pre-existing symptoms. Enthesitis and dactylitis are specific disease manifestations related to psoriatic arthritis.
In OTEZLA clinical trials, the majority of the most common adverse reactions occurred within the first two weeks of treatment and tended to resolve over time with continued dosing. Adverse reactions reported in at least two percent of patients on OTEZLA 30 mg twice daily and at least one percent greater than that observed in patients on placebo for up to 16 weeks were diarrhea, nausea, headache, upper respiratory tract infection, vomiting, nasopharyngitis, and upper abdominal pain. The proportion of patients who discontinued treatment due to any adverse reaction was 4.6 percent for patients taking OTEZLA 30 mg twice daily and 1.2 percent for patients taking placebo. The most common adverse reactions leading to discontinuation among patients treated up to 16 weeks with OTEZLA 30 mg twice daily were nausea (1.8 percent), diarrhea (1.8 percent) and headache (1.2 percent).
OTEZLA is contraindicated for use in patients with a known severe allergic reaction to OTEZLA or other components in OTEZLA. Across the three PALACE studies, 1.0 percent (10/998) of patients treated with OTEZLA reported depression or depressed mood compared with 0.8 percent (4/495) treated with placebo; 0.3 percent (4/1441) of patients treated with OTEZLA discontinued treatment due to depression or depressed mood compared with none among placebo-treated patients. In the PALACE studies, 10 percent of patients taking OTEZLA, compared with 3.3 percent of patients taking placebo, reported weight loss of five to ten percent. It is recommended that patients taking OTEZLA have their weight checked regularly.
During the placebo-controlled phase of the clinical trials, the rate of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies, was comparable between placebo and OTEZLA groups. The product labeling does not require routine laboratory monitoring for patients taking OTEZLA.
"Patients and physicians have expressed their desire for a safe and effective therapy for psoriatic arthritis that has the potential to simplify patient management. Celgene is excited to be expanding our transformational science into the therapeutic realm of Inflammation and Immunology, with a new approach for patients with psoriatic arthritis," said Scott Smith, Global Head, Inflammation and Immunology, Celgene Corporation. "The FDA approval of OTEZLA is good news for patients and healthcare professionals who are looking for a different way to manage this disease."
OTEZLA® (apremilast) is expected to be available in the U.S. in March 2014 and will be dispensed through a comprehensive network of specialty pharmacies. For more information about OTEZLA distribution and the exclusive treatment support services (including reimbursement assistance and 24/7 nurse support), doctors and patients can contact Otezla SupportPlus™ at 1-844-4OTEZLA (1-844-468-3952) or visit www.OTEZLA.com for more information.