Research and blowing up motorcycles

One of the interesting things about this particular NANT meeting was the fact that they just received funding for another 5 years. So, this was an opportunity to review the comments by the reviewers who awarded them the funding and begin the process of shaping the next 5 years of neuroblastoma research. The last 4 or 5 years have been very interesting and a learning experience for all. One of the biggest challenges has been the disappearance of drug and it continues to be a problem into the foreseeable future.

It has not only been with the NANT. It has happened across the board for many orphan and/ or pediatric diseases. Neuroblastoma has been hit especially hard by this issue. In fact, other than MIBG, I can't think of any phase 1s that have not been plagued by this obstacle. What is the problem? It goes something like this:

New exciting drug is developed.
New drug looks promising in preclinical research.
New drug enters phase 1 and 2 trials in adults.
Neuroblastoma researchers begin preclinical research in neuroblastoma.
New drug looks very promising in neuroblastoma.
Drug opens in phase 1 trials in neuroblastoma.
Drug works great in neuroblastoma.
Drug fails to show much activity in adult diseases.
Pharmaceutical company stops making drug.
Children with neuroblastoma loose drug.

It is this pattern (or ones very similar) that have played out over and over in neuroblastoma. While it is frustrating to us, I can assure you that it is just as frustrating to our researchers. They dedicate a good portion of their life and their research over a period of many years into these drugs to hopefully see them help kids with neuroblastoma - only to see the drug disappear simply because the market is not big enough. Drugs like PZA and CEP-701 are somewhat recent examples of phase 1 and 2 trials that have had promising results where the drug supply has disappeared but I can tell you that their have been many others behind the scenes that probably have not even hit your radar. I can think of 4 or 5 trials that would be open right now if it was not for drugs that disappeared after the protocol was written but before the trial official opened. It is terribly frustrating.

Over the years, the NANT has been very nimble and began focusing on drugs that are approved by the FDA and readily available. This is working well where there is a drug that can hit the target they are trying to achieve. However, there is not always a drug readily available that provides the particular effect that they are looking for. This is especially tricky when your are putting combinations of drugs together. This is where the decisions become very difficult.

Think of it kind of a like a war and think of the drugs like the different type of bombs you can use. The bad people (representing the neuroblastoma) are hiding throughout the city(representing our children) You can't drop the atomic bomb. You will destroy the city (and the child). You have to use a combination of different bombs and missiles to get the bad guys. You find out that most of the bad guys are hiding in a building. Therefore, you use an Irinotecan bomb to blow it up. You find out that , although you killed a bunch of bad guys, several survived by escaping out the back door into cars. You then use a bunch of little Temador missiles to begin taking out the suspected cars. You successfully kill some of those bad guys but, still, some escape on motorcycles. Unfortunately the motorcycles are too fast for the Irinotecan and Temador bombs so we need a special missile that can target these bad guys on the motorcycles. Unfortunately, there isn't a missile that has been developed that can target a motorcycle specifically. However, you know if you could blow up these motorcycles you could take this strategy from one city to another to get all of the bad guys.

So, you begin to build a special missile to go after motorcycles.

You build something and it works, however, you can't get a single company to manufacture it because it just doesn't make them enough money.

This is essentially how it is happening in neuroblastoma research. We are trying to blow up these dang motorcycles and, most of the time, there is just simply not a drug out there in the real world that will shut off this escape root. So, we end up taking chances and unfortunately, in the name of the almighty dollar, we keep losing.

Unfortunately, for one reason or another, it just doesn't make financial sense for big pharma to blow up motorcycles.

I can think of two phase 1 neuroblastoma trials that this happened to in the last year. I can think of three phase 1 and 2 trials that are currently in jeopardy because of the possibility of the drug disappearing. I can think of 5 or 6 clinical trials in neuroblastoma that did open last year because of this type of drug issue. Finally, I can think of 100 trials I could open tomorrow if drug supply has not an issue.

Make no mistake. This is a huge problem in neuroblastoma and a huge challenge.

So, as we begin to shape what the next 5 years of neuroblastoma research will look like, what do we do? How do we stop this from happening? How do we insure that these promising therapeutic options move forward?

There is no easy answer and this is one of the important considerations that I can assure you that everyone is taking under careful consideration.

Sometimes I wish purpose was easier.