Very well expressed. From AVXL board.
To all the good checkers players out there, watch some chess moves...
At the end of every commercial for an approved drug, you will hear a long list of “talk to your doctor if you experience any of the following:” disclaimers. Here’s what a Lilly clinical VP told me about how those “side effects may include” warnings get included in the commercials:
“Other BP’s test the drugs (once approved and available) on samples of people with the 10 top ranked most common complaints in medicine - changes in mood, sleep patterns, blood pressure, nausea, vomiting, changes in bowel habits - diarrhea/constipation, blurry vision...
Then, they test the drug on a sample of people who are on the top 10 most widely prescribed medications to look for “interactions” - do not take if you are currently taking blood thinners, anti-depressants, blood pressure medications, cholesterol meds, sleeping pills, thyroid meds, ...
And then, they tie it up with a neat little bow disclaiming every common condition: Do not take if you have diabetes, have experienced a cardiac event in the past (including murmurs, flutters, arrhythmias) have diabetes, history of seizures, are pregnant or may become pregnant...and so forth.”
So, it appears that every drug HAS all of these side effects. The fact is that none of these are found during the trial/testing phase because new drugs are treated in very select people with no complicating factors in order to try to get a 1 to 1 correlation of efficacy of the drug to the indication without noise distortion. The FDA does not make companies test against all other possible interactions before approval in case you haven’t noticed. They want to get a sense of the purest possible cause-effect relationship between a drug and efficacy and side effects caused only by that specific compound.
Attention...
It is the other BP’s doing strategic business which make the case for so many possible “outside” factors entering into the picture, that we are all left with the impression that every drug is just too dangerous or unpleasant to warrant taking it. It’s smart business - give the appearance that these are side effects of the actual drug alone. And all BP’s do it. It called “giving a clean drug side effects” if it works. (And don’t forget: do not use when operating machinery or mix with alcohol...I think that pretty much covers everything - DO NOT TAKE THIS DRUG EVER/ANYBODY!)
Here’s the chess move:
If Dr. Missling/Anavex and the SAB are able to show IMPROVEMENT in the most common areas of unwanted effects experienced by the vast majority of people, does that not “disarm” the coming attack from BP? So far, A2-73 COULD/MAY/MIGHT help treat certain indications affecting certain segments of the population (older - ALZ, younger - Rett, mid-age - PD), which won’t be known until after trials are performed and completed. But, if you are confident in the probable outcome of your trial (KEM analysis), and you gain approval, what kind of protection can you put into place against other BP’s hurting your market with their bag of pre-loaded contraindications? One way might be to offer clinical research that area’s most affected are actually improved by your drug. So let’s see, we have insomnia off the list, and mood changes in the “elevated” and therefore positive column. Add to that: improvement in cardiovascular areas of risk such as elevated blood pressure, and take seizures off the list...
You see where I’m going - the case I’m building.
So, if we can remove blurry vision - Shout out to MAC!!! - and get risk of stroke (which also involves high blood pressure), off the list, we simply need to address gastric effects (the gut biome gambit might turn something up there), and what is left is safe for every one (btw, someone mentioned high blood pressure affects our brave Rett heroines, and, I’m sure there is cross over in the AD/PD population of many of the common symptoms). No contraindications.
Then, add RWE, and the public feedback portion of the new transparent clinical trial reviews (a window into how the sausage is made) and you have a recipe for one helluva successful drug launch - ONCE EFFICACY ABOVE SOC IS ESTABLISHED.
That’s when people would clamor for it - especially in these devastating CNS diseases with no effective treatments. Just show the patients and caregivers that they (both) will sleep better, be happier, not be at increased risk for MI or stroke - possibly lower that risk, possibly improve vision, but not blur it, possible normal gastric ramifications...this is all symptom related, but it’s all good, even great!
Check mate; cocktails for everyone!
I think Missling is not letting us down - our own shortsightedness is. I do not agree that the only strategy is “start the trials and see what we got”. That’s checkers thinking; just think one jump ahead. Recipe for a thoughtless loss. If we get to the wall and get “kinged” or “crowned”, what the heck good is it if someone is waiting to immediately take back your achievement by jumping your king on the very next move? These strategies are all set up and ready to go as attested to by BP employees, and they’re legal, and make good business sense.
Does anyone want to win this “game”? I think Missling does. Does anyone want to think longer term and patiently to guarantee we still have options to succeed and win 10 moves down the road? I think Missling does.
Don’t move until you see it, right?
Looks like a lot of smaller pieces are coming together for a marvelous end game to me. Never mind the middle ground - that’s where most people/players/drug developers/BP CEO’s have made their fatal errors in the past.
Just mvho,
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