New strategies to treat pain are sorely needed, especially in light of the mounting problem with prescription opioid abuse. Anti-NGF antibodies represent a completely novel approach in analgesia: they sequester NGF, one of several inflammatory agents released by an inflamed joint and a major factor involved in sensitizing nerve cells and inducing pain. NGF binds its high-affinity receptor, TrkA, on peripheral sensory nerves, activating the thermosensitive ion channel TRPV1, which is also sensitized by noxious heat and certain chemicals, including capsaicin, and which contributes to pain following tissue injury. Mast cells also express TrkA, so an NGF-binding antibody would also block pain responses mediated by proinflammatory molecules secreted by these cells (Nat. Rev. Rheumatol. 9, 654–664, 2013).
Despite the seemingly solid mechanistic rationale underpinning this new opioid-free pain management route, safety concerns have made it difficult over the years to bring anti-NGF antibodies to market. The recent discontinuation of fulranumab was a result of reprioritization rather than safety issues, according to a Janssen press release, and Thousand Oaks, California–based Amgen has yet to reveal whether it will be carrying phase 3 trials forward. But the decision means only two anti-NGF antibodies in late-stage development remain.
This is a preview of subscription content, access via your institution