Tanezumab

Tanezumab is a humanized monoclonal antibody (IgG2) against anti-Homo sapiens nerve growth factor beta (NGFB). Tanezumab is used for the treatment of pain, especially osteoarthritis. The active ingredient is currently (2020) still the subject of clinical research.

The nerve growth factor belongs to the family of growth factors. During embryonic development, it induces the differentiation and proliferation of nerve cells, and in adults, their sprouting after injury. NGF is essential for the survival of sympathetic and sensitive neurons, since neurons enter apoptosis when the protein is missing.

Inflammation, peripheral nerve injury and chronic nociceptive and neuropathic pain lead to elevated levels of NGF. By binding to tropomyosin receptor kinase A, NGF releases inflammatory mediators. NGF induces the sprouting of nerve fibres (A genetically engineered form of NGF has been approved by the European Medicines Agency (EMA) for the treatment of keratitis neuroparalytica (ICD-10: H16.2)).

Tanezumab is the first NGF inhibitor in advanced clinical trials in patients. Tanezumab inhibits the action of NGF and thus provides pain relief. The transmission of pain signals from muscle, skin and organs to the central nervous system is prevented.

The antibody blocks the binding of NGF to two receptors that are important for the perception of pain. In a phase II study (safety and dose finding) with 440 volunteers, a pain reduction of 45 to 62 percent was achieved in patients with severe joint arthrosis. A total of several placebo-controlled studies with around 7,000 test persons are currently underway on the efficacy of the drug. In 2010, one phase III study had to be discontinued because 16 patients developed progressive arthrosis (dosage problem?). It was shown that a dose of 10 mg showed the best effect, but also the most side effects. The dose of 5 mg is based on a compromise between effect and side effects.

The American regulatory authority FDA has now granted Tanezumab fast-track status for patients with severe pain symptoms that cannot be sufficiently controlled by conventional means (including opioids) due to joint diseases, diseases of the lower spine or severe tumour-related pain.

The results of a long-term study suggest that Tanezumab is superior to the non-steroidal anti-inflammatory drugs (NSAIDs) that are classically used for treatment in the treatment of pain and the maintenance of physiological joint function, but not in the general course of disease.

1. Nair AS (2018) Tanezumab: Finally a Monoclonal Antibody for Pain Relief. Indian J Palliat Care 24:384-385.
2. Tive L et al (2019) Pooled analysis of tanezumab efficacy and safety with subgroup analyses of phase III clinical trials in patients with osteoarthritis pain of the knee or hip. J Pain Res 12:975-995.