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.