FDA Approves OTEZLA (apremilast) for the Treatment of Oral Ulcers Associated with Behçet’s Disease

Celgene Corporation announced that the U.S. Food and Drug Administration (FDA) has approved OTEZLA (apremilast) 30 mg twice daily (BID) for the treatment of adult patients with oral ulcers associated with Behçet’s Disease. OTEZLA, an oral, selective inhibitor of phosphodiesterase 4 (PDE4), is the first and only approved treatment option for oral ulcers associated with Behçet’s Disease, a rare, chronic, multisystem inflammatory disease that is difficult to treat.

“Oral ulcers are a recurring and debilitating manifestation that affects nearlyeveryone living with Behçet’s Disease,and have an important negative impact on the quality of life for these patients,” said Yusuf Yazici, M.D., Clinical Associate Professor, Department of Medicine, New York University Langone Health. “In the clinical trial, OTEZLA demonstrated improvements in measures of oral ulcers at week 12. OTEZLA has the potential to be a needed treatment option for U.S. patients and their physicians, who previously had limited options available.”

Behçet’s Disease, also known as Behçet’s Syndrome, affects approximately 5 in 100,000 people in the U.S. Oral ulcers, the most common manifestation of Behçet’s Disease occurring in more than 98% of patients, can be painful, disabling and negatively affect quality of life.

“We are excited to provide the first and only FDA-approved treatment for oral ulcers associated with Behçet’s Disease,” said Terrie Curran, President, Celgene Inflammation & Immunology. “This approval is a reflection of Celgene’s commitment to research in areas of high unmet need, including rare diseases such as Behçet’s Disease. We remain dedicated to further studying OTEZLA and its role in inflammatory conditions.”

The FDA approval was based on efficacy and safety results from the randomized, placebo-controlled, double-blind Phase 3 RELIEF™ study evaluating OTEZLA in 207 adult patients with Behçet’s Disease with active oral ulcers who were previously treated with at least one nonbiologic medication and were candidates for systemic therapy. Results showed OTEZLA 30 mg BID resulted in a 42.7 point reduction from baseline in the pain of oral ulcers as measured by the visual analog scale (VAS) at week 12, compared with an 18.7 point reduction with placebo. The proportion of patients achieving an oral ulcer complete response (oral ulcer-free) at week 12 was 52.9% in the OTEZLA arm and 22.3% in the placebo arm. The proportion of patients achieving oral ulcer complete response by week 6 and who remained oral ulcer-free for at least six additional weeks during the 12-week treatment phase was 29.8% in the OTEZLA arm and 4.9% in the placebo arm. The daily average number of oral ulcers during the 12-week treatment phase was 1.5 in the OTEZLA arm and 2.6 in the placebo arm (based on oral ulcer counts measured at baseline and at weeks 1, 2, 4, 6, 8, 10 and 12).

“Behçet’s Disease is a chronic inflammatory disease in which patients present with symptoms such as oral ulcers that can have a significant impact on daily life,” said Mirta Avila Santos, M.D., Executive Director, American Behçet’s Disease Association. “Today’s approval for OTEZLA marks an important milestone for people with Behçet’s Disease who have been eagerly waiting for treatment options for their oral ulcers.”

The most common adverse events observed occurring in ≥10% of patients in the RELIEF trial were diarrhea (41.3% with OTEZLA; 20.4% for placebo), nausea (19.2% with OTEZLA; 10.7% for placebo), headache (14.4% with OTEZLA; 10.7% for placebo) and upper respiratory tract infection (11.5% with OTEZLA; 4.9% for placebo). The safety profile was consistent with the known safety profile of OTEZLA.

OTEZLA is now approved for three indications in the U.S., including the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy, adult patients with active psoriatic arthritis and adult patients with oral ulcers associated with Behçet’s Disease. Since its initial FDA approval in 2014, OTEZLA has been prescribed to more than 250,000 patients with moderate to severe plaque psoriasis or active psoriatic arthritis in the U.S.

OTEZLA is available in the U.S. and is dispensed through a comprehensive network of specialty pharmacies.

Celgene anticipates a regulatory decision for OTEZLA in oral ulcers associated with Behçet’s Disease from the Pharmaceuticals and Medical Devices Agency in Japan in the second half of 2019. The Company also submitted a Type II Variation to the Marketing Authorization Application earlier this year seeking approval in the European Union.