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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 5

By Charles-Edouard!

Yes...It's been exactly 1000 days since 4/7 was authorized by the Morlat Report. Our practical guide dates from 2014: print it and put it under the nose of your doctors. At Homo Parisianus, 4/7 is becoming more and more common... For the 1/7, it comes slowly... Remain the province, the chicks, the disconnected of the Tout-Paris-Qui-Compte. One could have reproached Quatuor for a prejudicial waiting period: 3-4 years lost. Very formally, this is not the case: Morlat, who could have been blamed for this wait-and-see attitude, has in fact explicitly authorized 4/7, as early as 2017! Slow and proactive at the same time: Quatuor is here, in French: It's a flat-out success: we'll come back to it!

DTG-25 mg: Basic Dose (BD) and Rescue Dose

The FDA considers 3 groups: group 1: patients with no problems, group 2: multi-resistant patients, with no solution, group 3: multi-resistant patients, with options. Here, there is no need to dwell on group 3. Group 2, in the USA, is 5000 patients. Out of 1.1 million S+ patients, this is very few, even negligible. The manufacturer could very well want to concentrate its marketing choices on group 1: that would make sense. However, it would make sense...

Let's call DB (Basic Dose, in mg) the oral dose necessary to zap a wild virus (not mutated). This base dose will deliver a plasma dose roughly corresponding to the IC95 (or IC90), the 95% (or 90%, respectively) inhibitory concentration (for DTG: 64 nanograms/mL).

Let's look again at this table published by ViiV, but from the perspective of RAL (raltegravir, aka Isentress ®). There are several primary mutations in red, including one with an FM (Multiplier Factor, FC) of 85. For patients in group 1, i.e. 99.9% of the market, if you want to be sure of your chances, you have to cover the red zones, including the highest one, which invites you to choose a dose of 100 times the DB! It is no longer surprising to see Isentress HD dosed at ... 1200 mg;

For secondary mutations (table 2), it is clear that even at 100 DB, it is so red that it will not work: even at 12,000 mg... If we have resistances elsewhere, the deadlock is total.

Fast Track or... bankruptcy...

Offering a solution to group 2 is very hard, and at the cost of marginalization on the market. However... For ViiV, is an ABSOLUTE priority. Why is that? Because:
1 - it is possible, certainly the dose is high, but it is playable
2- it's urgent: ViiV is on the verge of bankruptcy: its drugs are old and will soon be genericized, ALL of them, which means a drop of 80 to 90% in turnover! Do you know many companies that are resisting to such a downturn?

Solving the problem of group 2 will save ViiV from a predicted industrial disaster: thanks to the (super) fast track, accelerated approval by the FDA. For ViiV, it is vital. On the other hand, we can observe that Gilead has been rather late to release the TAF. Big Pharma delays to perpetuate its profits, but sometimes accelerates to save its skin.

But let's look at the table of secondary mutations, for DTG this time, with 50 times the DB, that's enough! And moreover, in the clinic (SAILING trial), it will do it! For the FDA, for the DHHS (US guidelines), it's a great move! Whoever solves the problem of group 2 will not be objected to in the slightest. Translated into good French, the ASMR, delivered by the commission of transparency, will be rather nice! It is published here:


If you approach the MA with an ASMR of 5, you'll be passed over, with an ASMR of 4 you'll pass, but the economic committee will take its time. If you have an ASMR of 3 and a market price, it will go fairly quickly. This is in fact what happened, see the Efficiency Opinion (May 2014)

The naive patient... Indeed, quite naive!

So, you, patients of group 1, naively thought that the dose had been thought for you, and that by chance, by inflating a little, we solved the problem of group 2. Well, no... It is the opposite: we solve the problems of group 2, in priority, and by deflating a little, we will solve group 1(who can do more can do less), but regardless of the FM needed for group 1 (FM from 3 to 5).

INI	DTG	RAL	EVG
FM Max group 2	50	500	50000+
Dose for group 2	2 x 50 mg	unusable	unusable
FM Max group 1	3	90	500+
Dose for group 1	50 mg	1200 mg	with booster
Prior eligibility for group 1 (only)
7/7 Therapy	YES	YES	YES with booster
Bitherapy 7/7	YES	YES ?	NO
Monotherapie 7/7	YES	NO	NO
Eligible 4/7	YES	YES (?)	YES (?)
Eligible 3/7	YES	NO	NO
Eligible 2/7	YES	NO	NO
Eligible 1/7	YES (?)	NO	NO
Eligible half dose	YES	NO	NO

And this is how they will get a MA with a price of 600 Eu. for 25 DB (50 mg). In practice, this will make 1200 Eu. for the rescue treatment: the 50 mg at 600 Euros is the market price for the first line and, at 2 x 600, in the market price for the second. Nothing and nobody will find fault with this.

That is... 12 Euros per DB/month

You, patients of group 1, without the slightest risk to switch to group 2, you only need 5 DB (counting very large). But here's the thing, ViiV, they are not stupid: they are not going to propose a drug at 5 DB but at 25 DB... Of course, in vivo, one can obtain different results. And they are remarkably discordant: Mono-DTG which works very well here, in humans (and we'll watch what Morlat says about it), and, surprise, very badly in monkeys (Mesplède article). Whatever, what concerns us is us...

We'll see next time why and how ViiV is going to optimize its income a super max, at your expense. To get a head start, try to imagine the extraordinary loss of income for ViiV, if they had chosen 10 mg

In the news

- Stromae is better! A time forced to an artistic retreat after almost ending his life during a depressive episode triggered by a drug intolerance'I made a reaction to Lariam, an antimalarial, super super serious, he added in late 2017. I had a psychic decompensation. It's really not nice.' Really??? Does drug-induced depression exist? We don't even need Lariam, EFV, RPV, DTG are more than enough... Not to mention the interactions between drugs...

- Chlamydia: a vaccine is being developed. For an immunizing disease (you get over it, and then you don't get it anymore) such as measles or Ebola, it is well conceived. For non-immunizing diseases (HCV, HIV, Tuberculosis), it is already much less obvious! That the BCG is useless, they did not shout it from the rooftops! As for HIV, don't expect too much from the ANRS in this matter (given the mishmash of personal conflicts on the subject). On the other hand, finding an invariant, such as TAT OY, is already more encouraging: this is the BIOSANTECH approach. We will see...

The French genius

One can hold one's breath, but one comes out under high blood pressure! Film noir under a blazing sun, a dry hell under a torrent of sweat... No need for a big budget to make a cult film, a film that the Americans will remake. Well... Unless they remake QUATUOR, they'll let us have the exclusivity of the extraordinary economic gain, a real gold mine for us alone. That's just fine!

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good weekend, good stuffing and not too many meds ... Huh?