Tanezumab, a recombinant humanized mAb against nerve growth factor for the treatment of acute and chronic pain

Abstract

Persistent pain represents a major health problem, and most current therapeutic approaches are associated with unwanted effects and unsatisfactory pain relief. Therefore, an urgent need exists to develop more effective drugs that are directed toward new molecular targets. Nerve growth factor (NGF) is involved in pain transduction mechanisms, playing a key role as a master switch in many chronic and inflammatory pain states; the NGF ligand and its receptor TrkA constitute well-validated targets for pain therapy. Tanezumab (RN-624), a first-in-class recombinant humanized mAb targeting NGF, is being developed by Pfizer Inc for the potential treatment of pain associated with several conditions. In preclinical studies, tanezumab, and its murine precursor muMab-911, effectively targeted the NGF pathway in various chronic and inflammatory pain models. Phase I and II clinical trials in osteoarthritic pain and chronic lower back pain demonstrated good efficacy for the compound, as well as a good safety and tolerability profile. Given that tanezumab is an antibody, the drug demonstrates the general advantages of this class of products (including good specificity and favorable pharmacokinetics), and also appears to be particularly well suited for targeting the chronic and inflammatory-mediating pain actions of NGF and its receptor system.