AN2728 and AN2898 Ointments Demonstrate Safety and Efficacy in a Bilateral Study of Atopic Dermatitis

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JSID Abstracts / Journal of Dermatological Science 69 (2013) e1–e46

P04-15 AN2728 and AN2898 Ointments Demonstrate Safety and Efficacy in a Bilateral Study of Atopic Dermatitis Lee Zane ∗ , Tatiana Gogoleva, Frederic Heerinckx, John Jermano Anacor Pharmaceuticals Background AN2728 and AN2898 are boron-based phosphodiesterase-4 inhibitors, well-suited for the topical treatment of inflammatory skin disorders. AN2728 has previously demonstrated safety and efficacy in several Phase 1 and 2 trials for mild-to-moderate psoriasis. This study was design to determine their safety and efficacy in the treatment of mild-to-moderate atopic dermatitis. Methods Multicenter, randomized, double-blind, vehicle-controlled, bilateral comparison study. 46 adult patients with mild-tomoderate atopic dermatitis were randomized (1:1) to receive either AN2728 Ointment, 2% vs. Ointment vehicle or AN2898 Ointment, 1% vs. Ointment vehicle applied BID to two similar target lesions on the trunk or extremities for 6 weeks. Lesion severity was measured by the Atopic Dermatitis Severity Index (ADSI). Results Co-primary endpoints: Compared with vehicle, lesions treated with AN2728 as well as those treated with AN2898 achieved greater improvement in ADSI in a significantly higher proportion of patients after 28 days (68%, P = 0.02 and 71%, P = 0.01, respectively). AD lesions also had a greater decreases from baseline mean ADSI score on Day 28 when treated with AN2728 (66%, P < 0.01) or AN2898 (68%, P = 0.02) compared to vehicle. Further, the proportion of lesions achieving total or partial clearance (ADSI < = 2) at 28 days was higher following treatment with AN2728 than vehicle (52% vs. 16%) as well as with AN2898 (48% vs. 33%). Treatment appeared safe and well-tolerated.Conclusion Overall, AN2728 Ointment, 2% and AN2898 Ointment, 1% are each effective in reducing the severity and signs of atopic dermatitis lesions and appear safe and well-tolerated. http://dx.doi.org/10.1016/j.jdermsci.2012.11.402 P04-15 AN2728 and AN2898 Ointments Demonstrate Safety and Efficacy in a Bilateral Study of Atopic Dermatitis Lee Zane ∗ , Tatiana Gogoleva, Frederic Heerinckx, John Jermano Anacor Pharmaceuticals Background AN2728 and AN2898 are boron-based phosphodiesterase-4 inhibitors, well-suited for the topical treatment of inflammatory skin disorders. AN2728 has previously demonstrated safety and efficacy in several Phase 1 and 2 trials for mild-to-moderate psoriasis. This study was design to determine their safety and efficacy in the treatment of mild-to-moderate atopic dermatitis. Methods Multicenter, randomized, double-blind, vehicle-controlled, bilateral comparison study. 46 adult patients with mild-tomoderate atopic dermatitis were randomized (1:1) to receive either AN2728 Ointment, 2% vs. Ointment vehicle or AN2898 Ointment, 1% vs. Ointment vehicle applied BID to two similar target lesions on the trunk or extremities for 6 weeks. Lesion severity was measured by the Atopic Dermatitis Severity Index (ADSI). Results Co-primary endpoints: Compared with vehicle, lesions treated with AN2728 as well as those treated with AN2898 achieved

greater improvement in ADSI in a significantly higher proportion of patients after 28 days (68%, P = 0.02 and 71%, P = 0.01, respectively). AD lesions also had a greater decreases from baseline mean ADSI score on Day 28 when treated with AN2728 (66%, P < 0.01) or AN2898 (68%, P = 0.02) compared to vehicle. Further, the proportion of lesions achieving total or partial clearance (ADSI < = 2) at 28 days was higher following treatment with AN2728 than vehicle (52% vs. 16%) as well as with AN2898 (48% vs. 33%). Treatment appeared safe and well-tolerated.Conclusion Overall, AN2728 Ointment, 2% and AN2898 Ointment, 1% are each effective in reducing the severity and signs of atopic dermatitis lesions and appear safe and well-tolerated. http://dx.doi.org/10.1016/j.jdermsci.2012.11.403 P04-17 Antiphospholipid Antibodies in Patients with Cutaneous Polyarteritis Nodosa and Livedo Vasculopathy Naoko Ishiguro 1,∗ , Natsuko Wakabayashi 1 , Hisashi Yamanaka 2 , Satoru Shimizu 3 , Makoto Kawashima 1 1

Department of Dermatology, Tokyo Women’s Medical University, Tokyo, Japan 2 Institute of Rheumatology, Tokyo Women’s Medical University 3 Medical Research Institute, Tokyo Women’s Medical University Recently, it was reported that the presence of antiphosphatidylserine- prothrombin complex (anti-PS/PT) antibodies and/or lupus anticoagulant could serve as markers in cutaneous polyarteritis nodosa (CPN) patients. We examined antiphospholipid antibodies, including anticardiolipin antibodies, anti-␤2-glycoprotein I-dependent cardiolipin antibodies, lupus anticoagulant and anti-PS/PT antibodies, in 16 patients with CPN and in 9 patients with livedo vasculopathy (LV). Furthermore, we investigated␤- thromboglobulin, platelet factor 4, thrombin anti-thrombin III complex, D-dimer, protein C, protein S and thrombomodulin. As a result, we detected several kinds of antiphospholipid antibodies in 8 CPN patients and in 6 LV patients. IgG anticardiolipin antibodies were detected in each one of CPN and LV patient. Lupus anticoagulants were also detected in each one of CPN and LV patient. IgG anti-PS/PT antibodies were detected in 2 CPN and in 2 LV patients. On the other hand, IgM anti-PS/PT antibodies were detected in 8 CPN patients and in 4 LV patients. In addition, platelet activity and coagulation were abnormal in 5 CPN patients and in 6 LV patients. The thrombomodulin level was high in 1 CPN patient. In conclusion, IgM anti-PS/PT antibodies were detected more frequently than other antiphospholipid antibodies in CPN patients. It is suggested that IgM anti-PS/PT antibodies might act as a pathogenic factor for CPN, and that there might be a common pathogenic mechanism between CPN and some cases of LV, because IgM anti-PS/PT antibodies were also detected in about 40% of LV patients. http://dx.doi.org/10.1016/j.jdermsci.2012.11.404