Daily Archives: October 21, 2010

A pain drug discovery success story: anti-NGF therapy for osteoarthritis

ResearchBlogging.orgWith all the recent layoffs in Pharma, coupled with the axing of many analgesic drug development programs within these institutions, its nice to finally see a success (albeit of potentially short longevity — more on that later). The treatment is Tanezumab. Tanezumab is a humanized antibody against nerve growth factor (NGF). The biologic effectively blocks NGF interaction with its receptors, TrkA and p75. Basic researchers in the pain field have been working on the idea of blocking NGF function as a pain treatment for some time now. In fact, I’ve written about this before:

[in response to a question from Whimple] On your other question, are there examples where the clinical never would have been possible without the preclinical the answer is also yes. My example is not a good one because I likely would have been able to instigate a trial but it would have been much more difficult without the preclinical. On the other hand, the anti-NGF treatments for chronic pain are an excellent example of where it would not have been possible. We have known for a long time that NGF is involved in preclinical pain models and in human pain. We have also known that genetic mutations in humans that block NGF signaling (mostly receptor mutations) cause a terrible disease wherein people with the mutation have profound mental retardation, total lack of pain and inability to sweat. While it was the view of most researchers that this was due to a developmental issue, it was not known if blocking NGF signaling later in life would lead to similar deficits and this made any trial on anti-NGF therapies impossible due to very serious safety issues. After decades of preclinical work it is now known that anti-NGF treatments later in life do not cause similar problems and this animal work has made the safety issue a much smaller issue. So, due to literally thousands of papers on NGF signaling in animal models we have a good idea that these treatments will not cause devastating side effects in humans and these therapies are now late in clinical development. If they gain FDA approval I expect that they will become important treatments for chronic pain disorders. That is but one of several examples wherein animal work was absolutely neccessary to develop new pain treatments.

Onto the trial… (Lane et al. 2010 NEJM) The idea was to see if tanezumab would have efficacy for osteoarthritic knee pain. Rather than looking for efficacy in a currently treatable population, the investigators went for the gold and chose to study the effect of tanezumab in advanced osteoarthritis of the knee patients that did not receive pain relief from analgesics (mainly opiates) that are generally used in this patient population. They recruited about 450 patients and broke them into 6 groups: placebo and escalating doses of tanezumab. Treatment was given over 16 weeks and after that time frame they moved to open label. The results are striking: Continue reading