Apremilast was successful in significantly reducing oral ulcers in patients with Behçet’s Disease compared with placebo in a phase 3 study, according to findings presented at the 2018 American Academy of Dermatology Annual Meeting in San Diego.
A rare, chronic, multi-system inflammatory syndrome, Behçet’s Disease commonly manifests in oral ulcers that can be disabling and have a substantial effect on quality of life. According to a press release from Celgene, there is no approved treatment for Behçet’s Disease in the United States; additionally, apremilast (Otezla, Celgene) is not currently approved for the treatment of Behçet’s Disease in any country.
“Reducing oral ulcers, which are painful and can negatively impact quality of life, is an important goal in the treatment of people with Behçet’s syndrome,” Gulen Hatemi, MD, an associate professor at the Istanbul University Cerrahpassa Medical School, said in the release. “These findings suggest that apremilast, which reduced oral ulcers and oral ulcer pain, and improved disease activity in this pivotal study, has the potential to be a treatment option for patients with active Behçet’s syndrome with oral ulcers, for which few treatment alternatives exist.”
According to Celgene, apremilast significantly reduced oral ulcers in patients with Behçet’s Disease compared with placebo.
To analyze the effect of apremilast on recurring oral ulcers in patients with active Behçet’s Disease who were previously treated with at least one topical or systemic medication, the researchers initiated the phase 3 RELIEF trial. In the 52-week, randomized, placebo-controlled, double-blind study, 207 patients at 63 sites across 10 countries were randomly selected to receive either twice-daily doses of apremilast 30 mg or placebo.
The primary endpoint was the change in the number of oral ulcers over time at week 12. Secondary endpoints included change from baseline in pain of oral ulcers, Behçet’s Syndrome Activity Score, Behçet’s Disease Current Activity Index and Behçet’s Disease quality of life score at week 12.
According to Celgene, the apremilast group demonstrated statistically significant reductions in the area under the curve for the number of oral ulcers, compared with the placebo group, (P < .0001) at week 12. In addition, patients in the apremilast cohort demonstrated statistically significant improvements in oral ulcer pain (P < .0001), Behçet’s Syndrome Activity Score (P < .0001), Behçet’s Disease Current Activity Index (P = .0335) and quality of life (P = .0003).
The most common adverse events were diarrhea (41.3%), nausea (19.2%), headache (14.4%) and upper respiratory tract infection (11.5%). According to Celgene, this was consistent with the known safety profile of apremilast.
“The positive phase 3 findings in Behçet’s Disease reflect the unique aspects of the profile of Otezla 30 mg across inflammatory-related diseases,” Terrie Curran, president of Celgene Inflammation and Immunology, said in the release. “Otezla 30 mg has the potential to provide a clinically meaningful new treatment option for patients and doctors and to become the first product indicated specifically for the treatment of active Behçet’s Disease with oral ulcers.”
Celgene said it plans to submit supplemental New Drug Applications for twice-daily apremilast for the treatment of Behçet’s Disease with oral ulcers in the United States and Japan later this year. The company also plans to submit a Type II Variation to the Marketing Authorization Application in the European Union in 2019. – by Jason Laday
Disclosure: The researchers report support grants from Celgene. Hatemi reports receiving grant support and personal fees from Celgene.