Celgene Corporation has announced that results from long-term efficacy and safety analyses of the ESTEEM phase III clinical trial program of Otezla® (apremilast) were presented at the 73rd Annual Meeting of the American Academy of Dermatology (AAD) in San Francisco, California. OTEZLA is the Company's oral, selective inhibitor of phosphodiesterase 4 (PDE4) 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.
In ESTEEM 1 and 2, patients were randomized to treatment with OTEZLA 30 mg twice daily or placebo for the first 16 weeks. At week 16, patients either continued on OTEZLA or were switched from placebo to OTEZLA 30 mg twice daily through week 32. Patients initially randomized to OTEZLA who achieved a Psoriasis Area and Severity Index (PASI)-75 response (ESTEEM 1) or PASI-50 response (ESTEEM 2) at week 32 were then re-randomized to either OTEZLA 30 mg twice daily or placebo.
"Long-term data are critical in psoriasis, since patients may deal with this disease throughout their lives," said Jeffrey Crowley, M.D., Bakersfield Dermatology, Bakersfield, CA. "Having two-year safety results along with data showing that OTEZLA can provide long-term improvements in difficult-to-treat symptoms can be helpful for dermatologists and patients who are looking for different treatment options."
ESTEEM 2: 52-Week Data Observed in Patients with Nail, Scalp and Palmoplantar Involvement An analysis of data from ESTEEM 2 presented at AAD showed sustained improvements at week 52 among PASI-50 responders (patients who achieved a 50 percent reduction in PASI at week 32) in difficult-to-treat areas such as nails, scalp and the palms of the hands and soles of the feet (known as palmoplantar psoriasis). Among patients who had nail psoriasis at baseline with a Nail Psoriasis Severity Index (NAPSI) greater than or equal to one, 45 percent (78/175) of those treated with OTEZLA 30 mg twice daily had at least a 50 percent improvement in NAPSI (NAPSI-50) at week 16, compared with 19 percent (17/91) of those treated with placebo (P
Of those patients who had moderate to very severe scalp psoriasis at baseline, 41 percent (72/176) of those treated with OTEZLA 30 mg twice daily had a Scalp Physician Global Assessment (ScPGA) score of clear (zero) or minimal (one) at week 16, compared with 17 percent (16/93) of those treated with placebo (P
Among patients who had moderate to severe psoriasis on their palms and feet at baseline, 65 percent (17/26) of those treated with OTEZLA 30 mg twice daily had a Palmoplantar Psoriasis Physician Global Assessment (PPPGA) score of clear (zero) or almost clear (one) at week 16, compared with 31 percent (5/16) of those treated with placebo (P=0.0315). PPPGA score of zero or one achievement was sustained up to week 52 (n=4 of 4 patients) in patients randomized to OTEZLA who were PASI-50 responders at week 32.
PSOR-005, ESTEEM 1 and ESTEEM 2: 16-Week Palmoplantar Data
An analysis of PSOR-005, ESTEEM 1 and ESTEEM 2 found that OTEZLA improved palmoplantar psoriasis in a subset of patients with moderate to severe chronic plaque psoriasis who had palmoplantar involvement. Of those patients who had any palmoplantar psoriasis at baseline (PPPGA score of one or greater, n=427 across the three studies - 49 in PSOR-005, 254 in ESTEEM 1 and 124 in ESTEEM 2), a higher percentage of patients treated with OTEZLA 30 mg twice daily had PPPGA reduced to clear or almost clear compared with placebo at week 16 in all three trials [PSOR-005: 70 percent (19/27) vs. 32 percent (7/22), respectively, P=0.0072; ESTEEM 1: 63 percent (107/169) vs. 45 percent (38/85), respectively, P=0.0047; ESTEEM 2: 71 percent (55/78) vs. 37 percent (17/46), respectively, P=0.0003].
Among patients who had moderate to severe palmoplantar psoriasis at baseline (PPPGA score of three or greater) (n=144 across the three studies - 19 in PSOR-005, 83 in ESTEEM 1 and 42 in ESTEEM 2), a higher percentage of patients treated with OTEZLA 30 mg twice daily had PPPGA reduced to clear or almost clear compared with placebo at week 16 in PSOR-005 [67 percent (6/9) vs. 20 percent (2/10), respectively, P=0.0397] and ESTEEM 2 [65 percent (17/26) vs. 31 percent (5/16), respectively, P=0.0315]. There was no significant difference between the OTEZLA and placebo groups at week 16 in ESTEEM 1 [39 percent (22/57) vs. 31 percent (8/26), respectively, P=0.4912].
ESTEEM 1: Two-Year Safety Data
Long-term (104-week) results from the ESTEEM 1 trial showed that no new safety signals were identified in patients treated with OTEZLA 30 mg twice daily for up to two years (844 patients were randomized, 444 continued in the second year).
As with adverse events (AEs) reported during the first 52 weeks of exposure, most AEs reported during weeks 52 to 104 were mild or moderate in severity and did not lead to discontinuation. The most frequently reported AEs during the placebo-controlled period and the OTEZLA-exposure periods were diarrhea, upper respiratory tract infection, nausea, nasopharyngitis, tension headache and headache.
The exposure adjusted incidence rate (EAIR) for serious AEs did not increase with longer OTEZLA exposure, compared with the placebo-controlled period. There were no clinically meaningful changes in laboratory measurements identified over the OTEZLA 104-week exposure period. Incidence rates of major cardiac events, solid tumors, hematological malignancies and serious infections were comparable between the placebo and OTEZLA arms during the placebo-controlled period. No increase in incidence rates was noted with longer-term exposure to OTEZLA between weeks 52 to 104.
ESTEEM 1 and 2 are two large pivotal phase III randomized, placebo-controlled studies evaluating OTEZLA in patients with a diagnosis of moderate to severe plaque psoriasis for at least 12 months prior to screening, and who were also candidates for phototherapy and/or systemic therapy. Approximately 1,250 patients were randomized 2:1 to receive either OTEZLA 30 mg twice daily or placebo after an initial five-day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16- 32 in which placebo patients were switched to OTEZLA 30 mg twice daily through week 32, and a randomized withdrawal phase for responders from week 32 to week 52 based on their initial OTEZLA randomization and Psoriasis Area and Severity Index (PASI) - 75 response (ESTEEM 1) or (PASI)-50 (ESTEEM2).
PSOR-005 is a phase IIb, multicenter, randomized, placebo-controlled, dose-ranging study evaluating OTEZLA in patients with a diagnosis of moderate to severe plaque psoriasis for at least six months prior to screening, and who are also candidates for phototherapy and/or systemic therapy. 352 patients were randomized 1:1:1:1 to receive oral placebo or OTEZLA 10, 20, or 30 mg twice daily after an initial five- day titration period, for the first 16 weeks, followed by a maintenance phase from weeks 16-24 in which placebo patients were randomly switched to OTEZLA 20 mg or 30 mg twice daily through week 24.