Mark,...RE: Pennsaid etc.,
You want to deal with business issues, regulatory issues and DMSO toxicity issues.
DMSO toxicity issues are the least important to me, because I'm more concerned with other issues, primarily how fast we can expect consumers to adopt the product which will be determined by ease and convenience of use, portability and durability of the product, effectiveness, marketing, doctor adoption to prescribe and anything else that affects customer adoption and repeat use.
The paper you referred to on DMSO toxicity as a solvent in the semiconductor industry is interesting, but again slanted towards a different use than repeated application on the skin for many years. It does point out that a rat can tolerate it better than a monkey. If we assume we are genetically closer to monkeys than rats, the LD50 data indicates that if we drink two thirds of a beer bottle of DMSO, half of us would die,...if we drink the whole beer bottle of DMSO, only some big guys might survive.
The paper's discussion about DMSO in fruit is a little silly, considering they are talking parts per million,...so in black leaf tea (the highest amount of DMSO) there is 16 grams per tonne of drink. I imagine it would take a long time to steep and drink a tonne of tea and get 16 grams of DMSO in us, and rather difficult to drink enough to consume as much as a beer bottle full of DMSO,..perhaps you swelling up to the size of an elephant would kill you first? Similarly you would have to eat a tonne of cucumbers to get 0.12 g of DMSO in you. One application of DMSO on the knee could perhaps put 10 times that amount of DMSO into the cells around your knee.
More interesting is what happens to the membranes and proteins in our cells as DMSO passes through our cells. DMSO changes the properties of water. It also dissolves into the membranes of cells. It stops action potentials from firing in nerve cells,...that's its analgesic effect,...and it likely does that by causing the ion gate proteins in the membrane to change their shape so Na can not get from the outside to the inside of the nerve cell and cause the nerve to fire an action potential and send the pain feeling to the brain. If DMSO does this to these membrane proteins, it could cause changes in shape to many proteins by taking the place of water around proteins and making them dysfunctional. Of course you say it is only temporary,...and I agree,...but again we go back to long term frequent use which is not addressed in the paper. If someone has a WHMIS sheet for DMSO,...perhaps they could tell us what precautions we must take when handling it. My guess is you must wear gloves and avoid inhaling,...but I'm not sure.
Also discussed in that article is the fact that exposure to light, and although not specifically discussed probably heat, causes quick degradation of DMSO,...a problem for storage and ease of use. Leaving this in the car, purse or pocket on a warm day could destroy its effectiveness. It also biodegrades quickly. These problems could reflect on those labelling issues,...clearly this stuff has to be stored properly which could be a problem for an active individual.
The business issue you raise about Celebrex and Vioxx speaks perhaps to management, which I don't think I have ever discussed here. A big pharma, I'm reasonably sure, would have had Pennsaid (and maybe WF10 too for some uses) passed by the FDA by now, even with the negative perceptions some in the scientific and medical community have about DMSO, if they thought there was a good market for it and they could make a lot of money with it. For some reason the big pharma hasn't stepped up to the plate. That raises a red flag to me, but it is a business decision between J&J (or others) and DMX management. That decision has delayed revenue generation, and that concerns me, but I'm not sure what all the issues were.
My answer to your question about what did I think the reasons for HC to delay approval were, was buried in a post to Cal that day. I thought we were discussing amongst ourselves. I said I didn't know, except on the issues REK discussed, labelling and stupidity of HC. Labelling brings us back to useage and handling. If light and heat degrades the DMSO,...this could be a concern for labelling, efficacy and packaging, but that would just be my speculation for one of the labelling issues right now. Instructions for application also comes in here under labelling, and if it is inconvenient, messy or time consuming it would have an effect on adoption by the consumer. I think that we should push for mandatory publication of all correspondence between HC and drug approval applicants. Shareholders are lobbying down in the States for this now. If passed we could discuss specifics a lot easier than we can now.
Now to summarize my concerns, as I thought I had presented them in past posts. I am concerned about adoption of the product by the public. A pill is easy to take. Your assumption that everyone will understand that Pennsaid is better for them, and only an idiot would not see the difference is clear to me,...but is it to the rest of the population? For over twenty years, I have trained, worked with, supervised and watched over a large number of people who just made it, or never made it through high school. A substantial portion of these people are basically illiterate in todays world, and do not understand the issues we are discussing here, and do not follow directions very well all the time. These people are greater than 50% of your target group for Pennsaid. Many are old and easily confused. A pill is the easiest solution for them, although perhaps not the safest for long term use, but what percentage of all analgesic pill poppers develop serious side effects to the pills, and how many years does it take on average before the side effects become a big concern to the patient and doctor?
Doctors may at some time prescribe Pennsaid for the patient described above, but because the patient didn't want to take their shirt or pants off all the time to apply, because they left the bottle in the sun and the stuff was no good anymore, or they left the cap off and the air got to it and ruined it, or they spilled the bottle, or it takes too long to apply, or it causes a rash or stings, or it puts their skin and/or joint to sleep, or it messes up their clothes, or it smells funny, or their friends and relatives got a pill and it works good for them and this liquid stuff is just a pain in the butt,....etc., etc., etc,...there is a very good chance they will want to go back to the convenient pill until its side effects catch up to them. A high proportion of these people smoke cigarettes, drink alcohol to excess, and eat all the foods that are bad for them even after warning signs of diabetes, heart problems etc., etc. They won't listen to arguments of severe side effects, rotting guts, etc. They'll tell you that Aunt Molly has been on those pills for 40 years and that's the only thing that ever worked for her,...don't believe me? Fine,...we wait for a few years and see who's right.
Now of course you folks will laugh at the above and think I'm full of chit,...but think about the British experiment going on right now, of course it's insignificant because it's just the British and their system is different right? Think about the decrease in growth of early adopters of Pennsaid in the early trials in North America a year or so back,... only 3400 users at the end of the trial. If we got a double in enrollment every year (one patient or doctor recommending it to one friend each year) we should have had 8000 patients by the end of 4 years. Why didn't we get greater usage if none of these marketing concerns mattered, and this Pennsaid liquid was such a boon to medicine? We actually saw a decrease in rate of adoption in the last two years of the study,...why? Perhaps the doctors didn't want to fill out all that paperwork and dissuaded the patients, but then who are they thinking about then? I don't know,...but it worries me.
In any event, DMX continues to have strong believers who pushed this stock back from the precipice last Friday and made me some money,..I added a handful last Friday too, but didn't get quite the deal Cal got as I was obviously too worried. I too believe that the long awaited FDA announcement will cause this stock to jump, and it should continue with support until the next quarters earnings report comes. Then we'll see what the P/E is,...be nice if it at least turns positive. I hope nothing else goes wrong. So I worry some more. That's okay, I worry about a lot of stocks.
As far as WF10,...the articles I have posted to you supported the WF10 view. That's why I posted them to you. I am pro WF10 but I fear that Pennsaid may not provide enough profit, quickly enough, to support the rapid development of its use. Hopefully when the WF10 trial results are published, it will be possible to get a deep pocketed partner for it. That goes back to the business issues. I wish DMX management accepted a little less control, revenue and profit, in return for help with the FDA, HC, and marketing of both Pennsaid and WF10. Couldn't hurt the current shareprice,...could help us all in the pocket book.
That's my position,...I think I've said most of it before. DMSO is a very interesting molecule. I would have few concerns using it for my arthritis. WF10 is very interesting too. But I don't like the business developments that have occurred recently with this company. I don't like the fact that I don't know more about the problems HC has with Pennsaid. I would like to know more about the particulars of the patients in the early adoption trials that took place from 1996-2000. I would like to know lots more about lots of other things,...poor russett (gggggggggggggggg)
PS,...REK going public about the problems with HC and slamming them the way she did seems to be very much directed at shareholders, patients, doctors and the public. I get she is asking us for help. I posted that stuff about the pot smoking hepatitis victim the other day to show that camping out on Parliament Hill can do some interesting things to politicians willingness to speed up processes. Politicians seem to be able to do interesting things with HC and trials of drugs like pot, when public opinion is behind such things. Letter writing and petitions are nice,...but nothing would work better than arthritis protestors camping out on Parliament Hill,...suppose to warm up this weekend (gggggggggggggg) |
