Date: 2015-04-16
Type of
information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in The New English Journal of Medicine
Company: Celgene (USA - NJ)
Product: Otezla® (apremilast)
Action
mechanism:
- phosphodiesterase 4 inhibitor. Apremilast is an oral, small-molecule, selective inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. Otezla® is approved for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and for the treatment of adults with active psoriatic arthritis.
Disease: Behçet's disease
Therapeutic
area: Rare diseases - Inflammatory diseases
Country: Turkey, USA
Trial
details:
- BCT-001 is a phase II, multi-center, randomized, placebo-controlled, double-blind, parallel-group study of 111 subjects with active Behçet's disease. The study was mainly conducted in Turkey with a small number of patients from the U.S. After a screening period of up to 90 days, patients were randomized 1:1 to receive apremilast 30 mg twice daily or placebo for 12 weeks after an initial seven-day titration period, followed by a 12-week blinded extension, where the placebo group was switched to apremilast, and a 28-day post-treatment observational follow-up.
The primary endpoint of the study was the number of oral ulcers at day 85 (12 weeks). Less common manifestations of Behçet's disease, including genital ulcers, skin lesions, inflammatory eye disease, involvement of the gastrointestinal, vascular and central nervous systems, and pain from oral and genital ulcers, were chosen as secondary/exploratory efficacy variables or safety measures. (NCT00866359)
Latest
news:
- • On April 16, 2015, Celgene announced that results from a multicenter, randomized, placebo-controlled phase II trial (BCT-001) of apremilast (Otezla®) in patients with Behçet's disease were published in the April 16 issue of The New England Journal of Medicine . Behçet's disease is a rare, chronic inflammatory disorder characterized by recurrent oral and genital ulcers, which are considered a hallmark of the disease. Joint inflammation and recurrent skin and eye lesions may also occur. "Painful oral ulcers due to Behçet's disease are the hallmark of the condition and can have a significant impact on the lives of many patients. Currently used drugs for this condition may not control oral or genital ulcers in some patients or have potential adverse events that may limit their use," said Gulen Hatemi , M.D., Associate Professor, Cerrahpasa Medical School , Istanbul, Turkey . "The publication of these phase II data in The New England Journal of Medicine is critical to disseminating the findings to the healthcare professional community, to keep them informed of the latest developments in research on this rare, chronic disease."
- Findings from this study, including the primary endpoint (reduction in mean number of oral ulcers following 12 weeks of treatment), were initially presented at the European League against Rheumatism (EULAR) and the American College of Rheumatology (ACR) annual meetings in 2013 (P < 0.001). In addition to the previously reported results, the publication includes findings that the median (min, max) number of oral ulcers was also reduced following 12 weeks of treatment with apremilast compared with placebo (0.0 (0, 6) vs. 2.0 (0, 13), respectively).
- Findings from the full 24-week treatment phase were also included in the publication. After 12 weeks, patients in the placebo group were crossed over to apremilast treatment, and those in the apremilast arm continued treatment. For those treated with apremilast for the full 24 weeks, the decrease in the mean number of oral ulcers was evident by week 2 (0.3 at week 2 vs. 2.7 at baseline) and this decrease was sustained through week 24 (0.6). In the placebo arm, the mean number of oral ulcers was 2.9 at baseline and 1.7 at week 2. At week 24, following 12 weeks of apremilast treatment, the mean number of oral ulcers in the placebo group was 0.4.
- A decrease in pain associated with oral ulcers paralleled this decrease in ulcers over time. Mean pain scores, measured using a visual analog scale, decreased from 54.3 at baseline to 12.0 at week 2 and 9.7 at week 24. In the placebo arm, pain scores were 51.7 at baseline and 29.8 at week 2. At week 24, following 12 weeks of apremilast treatment, mean pain score in this group was 9.7.
Apremilast also significantly improved several measures of disease activity and quality of life at week 12. Mean change from baseline at week 12 was significantly better for scores on the Behçet's disease current activity form (-1.5 with apremilast vs. -0.1 for placebo; P < 0.001), the Behçet's syndrome activity scale (-21.2 vs. -6.0, respectively; P < 0.001), the Behçet's disease quality of life instrument (-4.5 vs. -1.6; P=0.040), and the short form 36 version 2 physical component summary (4.7 vs. -1.7; P=0.001). No significant improvement was seen in the short form 36 version 2 mental component summary (2.0 vs. 1.6; P=NS).
The safety and tolerability data for apremilast observed in this study were consistent with previously reported data from six other phase III studies of apremilast in psoriatic arthritis or plaque psoriasis. The percentages of patients who developed at least one adverse event (AE) during the placebo-controlled phase were comparable between apremilast (85.5 percent) and placebo (80.4 percent). Serious AEs occurred in two patients receiving apremilast and none receiving placebo. AEs leading to drug discontinuation occurred in four patients receiving apremilast and none receiving placebo. Nausea, vomiting and diarrhea were more common with apremilast compared with placebo. Based on these phase II results, Celgene has filed with regulatory authorities in Turkey and has initiated a global phase III trial of apremilast in this disease.
Is
general: Yes
