I hear everything you are saying. I hope someone responds to this with DEFINITE answers. Experimental tests look promising. Why such a long wait??
I bet we'll start getting real answers late this year on exon skipping, and this time next year on losartan and idebenonne.
I think the long wait is because you can't administer an experimental drug to humans in the US unless your experiment is approved by the FDA, and in Europe there is a similar regulatory agency. Since DMD moves slowly, the regulator's natural tendency would be to want the tests to run for years before concluding that the drug is safe and effective. The FDA is hypervigilant about experimental drugs because of abuses by big Pharma companies in the 50's and 60's which used the previous exemption for FDA approval for "experimental" drugs to covertly mass market things like thalidomide before safety had been established. Since DMD is lethal and there is no effective treatment, the FDA has the authority to be more flexible than they would be for yet another headache pill. Fortunately, the researchers, with help from PPMD and other patient advocacy organizations, have convinced the FDA to accept a six minute walk test after six months of the administration of an experimental drug as a valid measure of whether a drug helps or not. That regulatory decision has only happened in the last couple of years, possibly even last year. Now the experiments won't need to run as long, which makes them more economically feasible. As a result there will be more of them.I try to live in the hope that things which really help and buy time for all of us will start falling out in the next couple of years.
For more detailed info, go to clinicaltrials.gov, and search for "duchenne"
Why such a long wait? Is a valid question. There is no "really good" reason, other than paperwork and beuarocracy. I've spoken to many researchers in this field during my visits to the conferences and I have not received a response I'm comfortable with. It pretty much boils down to a tedious paper trail and long waits for responses and verification/validation from governing officials. The actual "work" involved may actually be 3 years and that is what they all say "3 to 5 years" because that is their point of view. In reality it ends up being 5 to 10 years when you add all the overhead. The next question then becomes, Is the overhead necessary? I heard some say yes but it can be improved many times over. So why isn't it? This is not the researchers problem since they have to follow rules set forth, but how do you go about changing such a process that has been etched in stone for so many years?
Why can't they have embedded FDA officials in the trials/research labs? Why does the verification/validation feedback need to take so long? Does the results sit in a queue? Does it get picked up quickly and they have to spend the time understanding it. If so why can't they be involved during the whole process so there is no learning curve? If all this overhead doubles the time it seems to be a valid area for performance improvement.
Paul: I'm not quite sure what you meant when you said "after one year of administration, it is a six minute walk." Does that mean after one year of administratrion, these drugs would quickly be approved and on the market? Forgive my ignorance. Terry Porcaro
I apologize for being unclear. For PTC 124, and one would expect, all other treatments to be administered for DMD patients who are still walking, the measure of success would be a comparison of the distance a patient could walk in six minutes at the beginning of the trial with the distance the patient covers in six minutes one year (12 months) after the trial begins.
See, for example: http://www.clinicaltrials.gov/ct2/show/NCT00592553?term=ptc+124&...
Unfortunately, it took literally years to convince the FDA that this was a good measure of success for a dmd drug. I don't know if that was the sole reason or even a significant reason for why clinical trial progress on PTC 124 has been so slow, but it's at least illustrative of the mindset that drug developers have to deal with.
Even if the drug developers establish that a given drug will achieve a statistically significant improvement in performance at the end of that year, then the FDA still has to review that data and approve it before a drug can be released.
Terry Porcaro said:Paul: I'm not quite sure what you meant when you said "after one year of administration, it is a six minute walk." Does that mean after one year of administratrion, these drugs would quickly be approved and on the market? Forgive my ignorance. Terry Porcaro