WHY BIOMARKERS BASED DIAGNOSIS WILL PROFIT TO GENFIT (by Gery DIVRY)

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After the announcement of the GENFIT success in biomarkers diagnosis program, it is interesting to consider the indirect effects of the arrival of this new screening method

Given the past few articles and publications the question of the real number of adult patients with NASH in industrialized countries is still debated 

The controversy over the true prevalence give us a large fork of values

12% to 17% according to the FDA

12% by GENFIT and INTERCEPT

2 to 5% by NIDDK  but their document is over dated to my opinion (2006)

6% according to other recents news

In fact it is difficult to get a clear view because the diagnosis is based on biopsy, few cases are diagnosed , and the prevalence given are usually based on studies performed on subpopulations of patients sometimes unrepresentative of the whole population (after autopsies CV accident, transplant donors, etc.)

The generalization of the diagnosis based on a simple blood test will reveal perhaps a panorama of much broader disease imagined to date.

I personally made the choice in my latest ratings from to rely on a 7.5% prevalence, and I looking forward to see what the first wide field testing will return.

The first gain for GENFIT and its competitors will be the easy diagnosis that will create the market.

But there is a second important benefit for GENFIT which is the preselection of ELAFIBRANOR responders before treatment.. 

Studies show that the expected gain for responding patients is very high

The results obtained in the study show that in the GOLDEN study population with NAS> 3 all parameters are excellent for responding patients. 

What is a reponding patient ? Regarding the definition used by GENFIT, a responding patient is a patient who reached the endpoint "NASH reversion without worsening of fibrosis ».

 It is not a compliant criteria, an histological improvement on NAS score by 2 pts could have been a more compliant way to selects responders but GENFIT criteria are generaly exigents

So we could say that it's normal to say that the results are good for the patient who has been cured  ! Demonstrate that the treatment worked well on patients for whom it worked can be seen as a taulological approach.  Notice that some financial analysts mentionned it.

As often what seems simple is not .. because there is some interest in determining the set of improvements of a drug for those who respond to treatment.

In an article in the 2012 World Gastroenterology Organisation Global Guidelines

On NASH we can read :

"The exact cause of NASH has not been formally clarified and it is almost certain that the etiology is not the same in all patients. Even if it is very closely linked to insulin resistance, obesity and metabolic syndrome, all patients who suffer do not show NAFLD / NASH and conversely all patients with NAFLD / NASH do not present insulin resistance, obesity and metabolic syndrome. "

To recall the philistines like me, etiology brings together the cause and the factors of a disease.

All NASH patients do not have the same cause or the same factors which implies to treat them with different medications.  What I remember from the GOLDEN study is that the  Elafibranor not intended to treat any type of NASH.

what is very intersting to notice is the lot of benefits of the ELAFIBRANOR treatment for respondig patients 

On histological parameters we can notice:

An average reduction of NAS score of 2.67 points, and in particular ballooning - 1.27

A drastic  improvement on fibrosis score  = - 0,67 pts  (the average improvement observed in all patients in the FLINT study treated with  OCA was only - 0.2 pts  in absolute and -0,3 pts relatively to placebo)..

Note that these two figures are not directly comparable, we should know the mean improvement in fibrosis score in the OCA responders only to compare. It is nevertheless an indicator showing the effectiveness of Elafibranor on fibrosis responders

 

Regarding serological improvements we note:

 

AST and ALP decreased significantly, the CK18  also which is an indicator of decreased cell death. The results are also good for diabetic and lipid balance.

In summary, the benefits liver, metabolic and cardio diabetes among responders are important. Elafibranor appears to be a drug designed to impact the metabolic syndrome as a whole.

But then, how to prescribe to patients who have NASH but whose etiology is sensitive to Elafibranor?

An ancient method would have been to prescribe widely and to have a look  after a certain time to see if there are improvements or not.

The problem with this method is that if only 35% of patients respond to treatment, we will raise unnecessary medication to 65% of the target population which poses a safety problem (risk / benefit bad) and an economic problem .

The cost of processing one million patients is high, especially if we know that we only cure 350 000. 

As yet this is what is practiced for many drugs, health  insurance negotiate a lower treatment costs in proportion.

Hopefully  GENFIT announces that it has developed a blood diagnostic «  a  Biomarker Compagnon »  that would identify, at an unspecified percentage but should be between 80 and 90% (if they are better than 90% that would be really excellent), the ELAFIBRANOR responding patients.

It is a revolution because there would be more than 10% to 20% of patients who would be cured for nothing and much less in terms of targeted general population.

Example:

Without prior diagnosis targeted a population of 1 million patients with NASH are treated, 350,000 are cared for and 650,000 are treated for nothing

With prior diagnosis only between 280,000 and 420,000 patients are treated with an uncertainty of 35 000 to 70 000 patients, who could be treated for nothing


This means that GENFIT, with what amazing diagnosis method , can go and negotiate a comfortable treatment prices with insurance agencies. It can guarantee them that 80% to 90% of patients, after selection, will actually take benefit from the drug. 

With this preliminary diagnosis, the treatment cost can be doubled while maintaining a still very important gain for the health system.


Do not doubt that the potential partners who discuss with GENFIT have already seen the interest of this diagnosis on the future drug prices and I think we will soon see the positive effects of this new paradigm on the value of the company.


A more complete analysis on biomarkers is available here  (by ALbert Wright):







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