On June 23rd, Pfizer announced that FDA put its Tanezumab osteoarthritis phase III program on hold, following reports of worsening disease among patients receiving the antibody, which targets NGF (nerve growth factor). This came as no surprise to us. As we wrote back in November, “Tanezumab has titanic potential, but there are looming safety icebergs”.

NGF is involved in many vital physiological pathways, not just in the nervous system but also in the immune and neuroendocrine systems. Thus it is likely that other toxicities should emerge once the molecule’s action is blocked. As we discuss in our report, based on NGF’s role, possible consequences of its inhibition include peripheral neuropathy, dementia or other central nervous system dysfunction, increased rate of infection, slow wound healing or metabolic dysfunction. In fact, some evidence of these adverse effects has already been observed in phase II. In addition, it is certainly disturbing that there is sufficient rationale to test recombinant NGF itself (ie, the opposite pharmacologic effect of Tanezumab) as a treatment for Alzheimer’s disease – and such trials are underway by other companies. If that strategy is effective, doesn’t it suggest that anti-NGF therapies such as Tanezumab may accelerate or predispose patients to Alzheimer’s disease?

Our report provides an in-depth discussion of the observed and theoretical safety concerns of Tanezumab based on the known role of NGF. The chronic pain market potential is enormous. Pfizer is pursuing seven clinical indications, with a combined market potential of up to $6BN in the US alone. Osteoarthritis, the most advanced clinical indication, represents about a third of that opportunity. Even if osteoarthritis is out of the picture, the opportunity for Tanezumab is still huge – should it safety profile permit…