NASH ! TREATMENT’S STRATEGIES AND COMPETITION (by Gery DIVRY)

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The NASH disease is not homogenous, it grows on a fertile ground which is steatosis, may worsens, and induces fibrosis which may extend to cirrhosis.


Drugs candidates have different strategies and Labs can claim targeting NASH when, in facts, they do not ! 

 NASH is a complex disease that scientists are only beginning to understand the contours and whose definition changes with the advance of scientific knowledge.

It is the consequence of a metabolic disorder that finds its soil in fatty liver(NAFL), a disease previously regarded to this day as benign, as reversible with a change in lifestyle.

If we list all the most advanced laboratories having made an announcement on NASH, it seems difficult for non specialists to evaluate the treatment strategy they promote.

In the purpose of popularization, i will try below to explain with analogies, who target what !

We can  compare the liver steatosis (NAFL) with the fertile soil. without it the NASH disease can’t prosper !

On that soil, a mushroom can grow up ! and we can compare the mushroom with NASH. Feet as ballooning and cap as inflammation !

When the mushroom is growing up, and after a while, some spots and scars appears on the mushroom cap. The older the mushroom is, the more spots ans scars increase.

As an analogy, the spots and scars can be compared to fibrosis and cirrhosis.

The purpose of the demonstration is to explain what are the most advanced drugs strategy and targets.


  • Some of the drugs are targeting mainly steatosis .. they argue that removing the fertile soil will prevent mushroom to grow and it seems logical, but what about the existing mushrooms. The most advanced drugs in this category are Aramchol (GALMED)  and Victorza (NOVONORDISK) and maybe OCA (INTERCEPT)


  • Some of the drugs are targeting mainly inflammation and ballooning .. they argue that removing the existing mushroom and preventing new mushrooms to appear will prevent consequences, no mushroom, no scars. The most advanced drug in this category is Elafibranor (GENFIT) but some of drugs are targeting inflammation only in a way to prevent fibrosis (they are mentioned below)


  • Some of the drugs are targeting only advanced fibrosis and cirrhosis, they act on inflammation consequences to clean the scars and spots on the cap, preventing liver death but they do not impact the fertil soil and the mushroom. as soon they stop the treatments, the scars can prosper again !  The most advanced drugs in this category are Simtuzumab (GILEAD), Cenicriviroc (TOBIRA), GR-MD-02 (GALECTIN),Emricasan (CONATUS) and maybe OCA (INTERCEPT)


The OCA (INTERCEPT) efficacy is debated .. One study seems to show effects on steatosis and fibrosis but very few effects on ballooning and inflammation (no significant NASH reversion). The other study (Japan) reveal no significants effects on fibrosis and NASH reversion. 



champignon analogy explain 2


The treatment strategy would be a combinaison of the targets depending of the severity of the disease.

  • A patient with advanced fibrosis or cirrhosis  would need an emergency treatment to stop the fibrosis, a chronic treatment to reduce or resolve NASH and a drug (or way of life modification)  to reduce steatosis.


  • A patient with mild or advanced NASH with no fibrosis or mild fibrosis  would need  a chronic treatment to reduce or resolve NASH and a drug (or way of life modification)  to reduce steatosis.


  • A patient with steatosis and suspicion of mild NASH could take a drug (or way of life modification) to reduce steatosis.


So some drugs candidates, presented as competitors by Analysts, are in fact complementary. 

The real competition is between the drugs presents in the same treatment strategy’s segments.

 





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