AUA 2004: Recombinant Human Anti-NGF Antibody

[MastCells]

Program#/Poster#: 363

Presentation Title: EFFICACY AND SAFETY OF RECOMBINANT HUMAN ANTI-NGF ANTIBODY IN THE TREATMENT OF IC

Author Block: Jordan D. Dimitrakov, Dorian Dikov. MEDICAL UNIVERSITY, Plovdiv, Bulgaria, LAGNY-SUR-MARNE, Lagny-dur-marne, France

Introduction and Objective: Nerve growth factor (NGF) -- a neurotrophic and survival factor for sympathetic neurons -- has been shown to play key role in the generation of neuropathic pain which is characteristic of interstitial cystitis (IC). NGF can lead to a rapid and large increase in the production of neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) which sensitize neurons and lower pain threshold. Increased NGF levels in inflammation can cause mast cell degranulation, thermal and mechanical hyperalgesia serving as a link between inflammation and hyperalgesia. NGF also reflects the fact that IC patients experience pain which has both a sympathetic and vascular component. We evaluated the efficacy and safety of therapy with recombinant human anti-NGF monoclonal antibody (rhu-anti-NGF) in a group of IC patients with significant nerve damage and neuropathic pain component who have failed numerous previous treatments. Methods: Thirty-three female patients diagnosed with IC in accordance with the NIH/NIDDK criteria were enrolled into the current study. Patients had had IC symptoms for a minimum of 1 year and had failed conventional triple therapy for IC (pentosan polysulfate + amitriptyline + hydroxyzine). Patients received daily subcutaneous injections of rhu-anti NGF for 1 month and self-injected weekly for additional 6 months. Urinary nerve damage marker levels (NGF, CGRP, VIP, NPY, MBP) were evaluated at baseline, 1 month, 3, 6, and 12 months. Results: At 1 month, 59 % of patient reported significant improvement which was sustained at 3 and 6 months in 50% and 47 % of patients, resp. At 12 months, 40 % of patients reported significant improvement in symptoms as compared with baseline. Levels of nerve damage markers were significantly lower at 1, 3, 6, and 12 months as compared to baseline (P<0.001)Side effects were mild and included pain at the injection site (70 %) and transitory rash (11 %) of patients. Conclusions: Recombinant human anti-NGF appears to hold promise as a valuable therapeutic option for IC. Further trials, evaluating rhu-anti-NGF, need to be performed in larger patient cohorts and compared to placebo.