This was originally published here, in French (link).
We provide this translation for your convenience. Practical aspects may differ where you live.
DTG-25 mg episode 2
By Charles-Edouard!
You are spoiled for choice! In Paris, there is a plethora:
https://charles-edouard-ma-liberte.blogspot.com/p/medecins-allegeurs.html
You have to wonder where you can be so stupid as to say that Eviplera is not for this: 100% success in ANRS-4D, and very popular practice in Paris/Marais.
The trauma of multi-dose rosuvastatin
This post follows our first episode: DTG-25 mg ep.1
Here is a story that every pharmaceutical manager should know. To get 50% more effect, sometimes you have to double, triple, quadruple the dose. In chronic diseases, this will increase the cost of the treatment quite a bit. And when it's a metabolic manipulation without any proven clinical interest, it may be a problem for the FDA, the health insurance company and the insurance company. To prevent them from looking too closely, the industry has found a way to avoid this: charge the same price whatever the dose. It increases its market share, without any problem for the health insurance company or the patients...
As long as it is reimbursed at 100%.
No chance, the medication is of a questionable and contested utility. It is only partially reimbursed or not at all... This is the case of statins, of which the most powerful(no one says useful) is rosuvastatin, a drug that inhibits blood sugar at a very high rate, but whose effect is not proportional to the dose. It inhibits more at 40 mg than at 5, but not eight times more... Whatever, they will market it at the same price. You can find the prices in the USA, for the different doses, on this comparative site. We can see that, more or less, the 40 mg is at the same price as the 5 mg.
So what did the smart guys do? They were prescribed 40 mg and cut the tablets in 4! And as the association of retirees echoed, all American retirees, forced by an iniquitous system, started to do it! That's as much loss of profit for AstraZeneca: they collected 5-7 billion dollars per year, but the price fouling must have cost them between 500 and 800 million per year! When you like it, you don't count, but when you count, you don't like it!
So, multi doses, yes, at a pinch, but the crushing of the price especially not! do you understand the logic?
You can offer multiple doses without cutting into your profits, what they really need to do is avoid price gouging. ViiV is going to work on this... The same dose/price strategy can be seen in the Bictegravir component (Gilead). To understand how extortion is the order of the day in this industry, just read this article: Decoding Big Pharma's Secret Drug Pricing Practices
DTG and the famous specifications
Even if it defends itself for reasons of responsibility, it is, to our knowledge, the only document from an administrative authority that can serve as a guide to the industry. As a result, this document is established as the one and only specification (CoP). If your file is satisfactory according to the CoP, you are in an ideal position to obtain the Holy Sesame (American MA). This is normal, after all.
The French approach, which simply comments after the fact, is doomed to failure: the Transparency Commission will certainly slap you on the wrist, you will be awarded an ASMR that is sometimes very unfavourable, and it will only cost you during the economic negotiation, but your MA will nevertheless be granted. So, because of the lack of construction, the ANSM cannot protect you in any way: they are pissing in a fiddle. The FDA is something else...
The FDA document expresses the expectations, and these expectations reflect the state of the art: it inhibits any progress, including in terms of dose. Under the pretext of protecting you, it protects the FDA, the industrialist, at the cost of an inescapable overdose, because it is the FDA document that orders the overdose.
To be considered worthy of FDA approval, the new molecule/drug must bring an anti-retroviral benefit to 3 groups of patients: these groups are
- treatment-naive, susceptible patients
- multidrug-resistant patients in therapeutic impasse
- multi-resistant with possible options
very precisely:
Group 1: Fully susceptible to all approved drugs, treatments, or prior therapies with a well-documented treatment history demonstrating no virologic failure.
Group 2: Drug resistance to multiple drugs and multiple drug classes. Unable to construct a treatment regimen capable of suppressing HIV RNA to levels below the limits of quantification of the test.
Group 3: Drug resistance present and able to construct a regimen capable of suppressing HIV RNAs to levels below the limits of quantification of the test.
(In some ways groups 2 and 3 are somewhat confusing)
In addition, the FDA does not consider that a new ARV can be used alone. All this is very restrictive and DTG developers will have no choice but to comply...
To be convinced, let's take the example of an Absolutegravir, whose definition we recall: a molecule against which no resistance develops, whatever the dose. An Absolutegravir is used like an insulin... Too low a dose, the CV goes up without developing resistance. In other words, the barrier to new resistance is infinite in height.
This Absolutegravir is an ideal situation and allows us to imagine variants. Here is a definition for a type of Quasi-Absolutegravir.
Under this QAG, and even in case of under-dosing, it is impossible to develop a new AMR (mutation associated with resistance); the eventual rise of CV only reflects an insufficient dosage. On the other hand, it has a (small) defect: there is a mutation that makes it 100% ineffective. This mutation cannot be acquired under QAG but may have been acquired under earlier, weaker X-gravir.
Such a molecule would be of phenomenal interest for Group 1, but of no interest at all for Group 2: this hypothetical QAG does not meet the CoC of the FDA: it cannot be marketed!
What a shame! Because it would be damn useful ! But even if it did exist (and we can even reasonably assume that it does) it would, in the long run, mark the end of profits for the manufacturer, who will only offer it as a very last resort.
Let's take another QAG-2. With this QAG-2, and even in case of under-dosing, it is impossible to develop a new AMR (mutation associated with resistance); the possible rise in CV only reflects an insufficient dosage. On the other hand, it has a (small) defect: there is a mutation that makes it 50% ineffective. This mutation cannot be acquired under QAG-2 but may have been acquired under earlier, weaker X-gravir. Here, this QAG-2 will meet the FDA CoC: it meets the needs of group 1 but also of the other groups, even if only partially. It will pass the review with flying colors. Obviously, we have to propose a dosage that meets the needs of group 2&3. This is exactly what the development team is going to do: in a presentation (see here, the source is here), they explain perfectly this double objective:
Frankly, you don't care about taking the right dose for a Genvoya® -resistant patient(and even then... it's not always right) when you don't have to!
Do you want to go into treatment with rescue Pentatherapy? No, that's ridiculous... So why take such a huge dose of DTG?
We'll see in a future post, how ViiV went about maximizing, at your expense, its financial efficiency, with impunity...
Judiciarization
Opioid crises in the United States: pharmaceutical officials prosecuted(Le monde)
In the news
- Plosmedecine protests against trials for the sole benefit of industry and to the detriment of a healthy scientific discussion: The Ethics of Switch/Simplify in Antiretroviral Trials: Non-Inferior or Just Inferior?
- Doravirin ® is ultimately not terrible: DRIVE-AHEAD Trial's results and the need of a right comparator drug.
The French genius
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good weekend, good stuffing and not too many meds ... Huh?
