New and Emerging Treatments in Pemphigus and Bullous Pemphigoid
Neil Korman, MD, PhD University Hospitals Case Medical Center
Cleveland, OH
Conflicts of Interest
• Director of Clinical Trials Unit at UHCMC - many conflicts - none relevant to this talk
• Consultant and Chair, Scientific Advisory Board, - Immune Pharmaceuticals
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Neil J Korman MD, PhD
Current Treatments for Bullous Pemphigoid • Topical and Oral Corticosteroids • Oral Anti-inflammatory Therapies – Tetracycline
Antibiotics, Niacinamide, Dapsone • Oral Immunosuppressive Therapies – Cellcept,
Imuran, Methotrexate • Intravenous Therapies – Rituximab, Intravenous
Immunoglobulins
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Emerging Treatments in Bullous Pemphigoid
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Omalizumab for Treatment of Bullous Pemphigoid
• 60 – 70% of BP pts have elevated serum IgE • 25% of patientss have linear deposits of IgE at the
epidermal BM on DIF • Omalizumab is a humanized monoclonal AB that blocks
binding of IgE to its receptors • Omalizumab is FDA approved for treatment of asthma
and chronic idiopathic urticaria
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Omalizumab for Treatment of Bullous Pemphigoid
JAAD 2014;71:468-‐‑74
• 6 typical (urticarial plaques and bullae) BP pts • All had either elevated IgE or eosinophil counts • All had steroid refractory disease and were dosed at 300
– 400 mg q 2 – 6 wks • 5/6 pts responded to omalizumab with no AE’s • 3/6 pts responded to monotherapy • In 2/6 pts eosinophil counts correlated w/ disease activity
AGENT MOA
Bertilimumab: Anti Eotaxin-1 mAb
Prevents Eotaxin-1-induced chemotaxis of eosinophils and neutralizes Eotaxin-1 in the circulation, preventing eosinophil migration
Mepolizumab: Anti IL-5 mAb Prevents IL-5 mediated release of eosinophils from bone marrow into blood
Complement Inhibitors Inhibits the deposition and activation of complement pathway
QGE031: Anti IgE mAb Antibody directed against IgE. Clinical trial discontinued due to side effects
New Biologics With Potential in BP
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Eosinophil Predominance in BP Inflammatory Process: Role for Eotaxin-‐‑1
Eotaxin-1 levels are increased both in sera and blister fluids
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Eotaxin-1 is up-regulated in BP serum and correlates w/ disseverity*
Eotaxin-‐‑1 Levels in Bullous Pemphigoid
† PV - pemphigus vulgaris
Eur J Derm 12:27-‐‑31, 2002 Clin Exp Immunol 166:145-‐‑53, 2011
An Open-‐‑Label, Proof of Concept Study Designed to Evaluate the Safety, Efficacy and
Pharmacodynamic Effect of Bertilimumab in Patients with Newly Diagnosed, Moderate to
Extensive Bullous Pemphigoid
Study Product: Bertilimumab
Indication: Newly Diagnosed, Moderate to Extensive Bullous Pemphigoid
Protocol Number Immune/BRT/BP-‐‑01
Phase: 2a
Principal Investigator:
Prof Eli Sprecher, MD, Professor of Dermatology, Sackler Medical School, Tel Aviv University, Tel Aviv, Israel
• Patients: 15 adults with newly diagnosed, moderate to severe Bullous Pemphigoid
• Primary Objective: o To evaluate the safety and
efficacy of bertilimumab in patients with newly diagnosed, moderate to severe BP.
• Secondary Objective: o To evaluate additional
efficacy measures and pharmacodynamic effect of bertilimumab
• Study design Open-label, single group
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Phase 2 Bertilimumab (Anti Eotaxin-‐‑1 mAb) Study
Additional studies as well as US IND are pending
• Randomized, placebo-controlled, phase 2, double-blind study of anti-IL-5 mAB in patients w/ BP
• Estimated enrollment: 30 patients • Intervention:
o Drug: mepolizumab (an-IL-5 antibody) • 750mg mepolizumab four times over four months
o Drug: Placebo • Saline placebo four times over four months
• Currently recruiting in Berne, Switzerland
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Mepolizumab in Bullous Pemphigoid
• Oral corticosteroids • Oral anti-inflammatory therapies – Dapsone,
sulfasalazine and pentoxifylline • Oral immunosuppressive therapies – Cellcept,
Imuran, Cytoxan, methotrexate • Intravenous therapies – Rituximab, intravenous
immunoglobulins, Cytoxan, corticosteroids, plasmapheresis
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Current Treatments for Pemphigus
Emerging Treatments and Clinical Trials in Pemphigus
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• Randomized, controlled, non-blinded 6 month trial of 46 PV patients given either prednisolone and azathioprine (2.5 mg/kg) or prednisolone and tacrolimus (0.05 mg/kg)
• All patients had same steroid taper over 10 weeks • Time to cease blistering and disease remission were
same for Tacro and azathioprine Rxd patients • Slightly more side effects in azathioprine group
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Pemphigus Vulgaris Treatment With Oral Tacrolimus
J Derm Treat 26: 90-‐‑3, 2015
AGENT MOA VAY 736: Anti BAFF mAb Prevents activation of B cell
activating factor, cell surface receptor on B lymphocytes
Ofatumumab: CD20 mAB mAB that binds to CD20, cell surface receptor on B lymphocytes
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New Biologics in Pemphigus
• VAY - 736 • Antibody to BAFF – B cell activating factor, a cell
surface receptor on B lymphocytes • Phase 2, placebo controlled study • Pts with mild – moderate PV • Intravenous infusion of VAY - 736 compared to
placebo – enrolling in the US and other countries • No results currently available
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Emerging Clinical Trials in Pemphigus
• Randomized, double-blind, placebo-controlled, study of ofatumumab in pemphigus vulgaris
• Ofatumumab is a human mAB directed against CD20 - dosed subcutaneously
• Phase 3 multicenter trial, half of patients will get placebo for the full 56 week study period
• Patients must previously been on prednisone > 20 mg daily and must have previously failed a steroid taper
• Primary endpoint is time to sustained remission on minimal dose oral corticosteroids
• Enrolling in US & other countries – no data yet
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Emerging Clinical Trials in Pemphigus
• Randomized study of Rituximab vs MMF in Pemphigus Vulgaris
• Phase 3 Double blind study • Patients will receive either Rituximab and MMF
placebo or Rituximab placebo plus MMF • Patients must have mod-severe PV • Patients must be on 60 – 120 mg of prednisone • Enrollment in this trial has not begun
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Emerging Clinical Trials in Pemphigus