Anti-Human Nerve Growth Factor (Tanezumab) (T824-GRP)

Nerve growth factor (NGF) is a neurotrophin that regulates the structure and function of responsive sensory neurons1. In particular, NGF is involved in the transmission and sensation of inflammatory and neuropathic pain2. NGF is elevated in patients with arthritis, pancreatitis, and prostatitis as well as in animal models of inflammatory pain3. Additionally, increased expression of NGF in injured or inflamed tissue is associated with increased pain while blocking NGF in animal models reduces signs of pain. Therefore, harnessing NGF for pain modulation via therapeutic antagonism is of interest for inflammatory disease management. An antibody-based analgesic would also potentially avoid the gastrointestinal and cardiorenal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and narcotics typically used for pain management and may also help avoid or delay surgical intervention. Tanezumab is a humanized and affinity matured form of antibody clone E34 that blocks the interaction between NGF and its receptors TrkA and p751. Tanezumab/NGF binding is extremely stable, with dissociation too slow to detect in both surface- and solution-based assays2. Kinetics assays show that NGF binds as one whole homodimer to one tanezumab arm2. An NGF dimer “half-saturated” with a single molecule of tanezumab can use its second subunit to bind either a second molecule of tanezumab or simultaneously bind TrkA or p75 in addition to tanezumab. Tanezumab significantly reduces knee pain, stiffness, and limitations of physical function in patients with osteoarthritis3 and may have some therapeutic effect on lower back pain 11.