DrJ asks a very good questions with respect to NGF (Nerve Growth Factor) or treatment thereof with an Anti-NGF. In 2010, there were a number of NGF inhibitors that were in Phase II/III. The most promising was tanezumab made by Pfizer for relieve of pain caused by a number of conditions (bone cancer, lower back pain, osteoarthritis etc.). It was suspended due to it probably working "too good" in patients suffering from osteoarthritis. Seems that some patients ended up having to have joint replacement due to excessive wear on the joint and not necessarily the joint that originally had the most damage. Patients reported dramatic decrease in their pain and probably assumed their osteoarthritis condition had suddenly disappeared. Not so! It just made them more active and therefore the excessive joint wear.
Too the question that DrJ posed. NGF is something that the body needs and is used to maintain neuronal health. Without it, your neurons die. But when inflammation takes place at the joints, the production of NGF is much greater than normal and stimulates the pain pathways to the brain. The idea, is that you disrupt the binding process of NGF with the pain receptors at the point of inflammation and therefore disrupt the pain pathways to the brain. What role does NGF play in the CNS, or better, what role does an Anti-NGF monoclonal antibody play in the CNS? That is a question that is unclear in the scientific community. I would compare this to the same hypothesis that is being made about Amyloid Beta Plaques in Alzheimer patients. We know it plays a role, but to what extent? That is the question and it is the question that the science community is struggling with at the moment (both on the roles of NGF and Amyloid Beta Plaques). Oh by the way, Medimmune voluntarily withdrew MED1578 their Anti-NGF in 2010 until the dust settled with Pfizer's tanezumab. I believe that the trial has started for some conditions again.
Does Medimmune have an Anti-NGF that they believe plays a role in pain management in the CNS? Have they learned more about MED1578 and it's interactions and particularly how it works in the CNS? Perhaps, we don't know and have not been told what conditions they are attempting to treat under the collaborative. They seem to be very secretive about what their programs are surrounding pain management.
What is of more interest to me and seems to have a bit more consensus around it, is that of an Anti-TNF inhibitor and it's role in pain management in the CNS. Most recently, I read through a paper that was written on the subject as it relates to arthritis pain and how pain had dramatically decreased with the administration of an Anti-TNF. The paper focused on the idea that most of the pain management was done in the CNS as there was no way the Anti-TNF could have acted that quickly at the inflammation site. Not entirely sure how the MAB crossed the BBB on it's own and I am assuming there may have been compromise in the BBB to have allowed this.
Now what makes this even more interesting, is that Medimmune was bought by AstraZeneca in 2007. AstraZeneca also bought Cambridge Antibody Technology at around the same time and merged them with Medimmune. Cambridge Antibody Technology were the original discoverers of Humira. Humira is owned by Abbott and they sell about $8.2 billion dollars a year worth of it for the treatment of rheumatoid arthritis (among some other conditions). Humira is an Anti-TNF. How does that get into the brain in efficacious quantities? Seems that we might have some common interests by some parties - wouldn't you think?
Pain management is an enormous market and dwarfs most any other drug market. The marketplace for the relieve of chronic pain is in excess of $20-25 billion per year. It may even be more, since many people do not use pain killers for extended amounts of time because of the side effects of long term usage. Could you imagine, if you could get an injections every 6-8 weeks for the relieve of chronic pain with next to no side effects?
With the size of the pain management market and BTI's unique ability to transport drugs (like Anti-TNF MAB's) across the BBB, one would think that we would be in a good position to extract some very good upfront pre-clinical dollars. We should have the ability to say to the interested parties: Look guys, this market place is huge, you know it and I know it. You guys are still fiddling around with what works and what doesn't work in the CNS. If you wanna stay in the game, you have to pay for the priviledge to do so. Not tying our cart to your specific horse. The upside for you is a blockbuster drug. Do you really think that you can be out of the game? On the street, we call this setup a "stickup".
Medimmune hasn't told us what the targets are, but when you look at their pipeline for the CNS, it deals only Anti-Interleukin 6 for pain/inflammation, but we know that MED1578 is part of the strategy (or at least was) and we know from third parties that the Anti-TNF is part of it as well. Suffice to say that MedImmune sees the need to take one of these three (if not all) across the BBB.