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A silent liver disease epidemic

As nonalcoholic steatohepatitis, or NASH, stealthily becomes a leading cause of liver transplants, drug companies are racing to develop treatments

By Lisa M. Jarvis

this article by Lisa M. Jarvis was published on NASH in C&EN

(Chemical and Engineering News) 

Volume 94 Issue 39 | pp. 46-52

Issue Date: October 3, 2016

This article is well writed, interesting because exploring many problematics of the disease but ...

When you read it you discover that, following the author, the only serious way to treat NASH seems to be the FXR agonists ( OCA and followers)

There is only a chapter "Beyond FXR" that let you imagine that some other exotic pathway to cure the disease exist. In this chapter GILEAD (again mainly on FXR), Bristol Myers Squibb, Galecto, Promedior, Allergan,Tobira and Arkana are mentioned.

But some most advanced drugs in the NASH pipeline like PPAR agonists, are not even mentionned ! 

Is it a deliberate and oriented choice, a lack of knowledge on the subject or a simple misfit ?, difficult to know, the author contacted by mail did not answered yet . 

The author can complete her knowledge on the NASH most promising drugs in reading the full list of trials on this site.  

Relying on the INTERCEPT's CEO interview promoting FXR agonist seems not enough to propose a complete NASH landscape to the readers.

If the author need more information on the not mentioned competitors like GENFIT  (in phase 3 as Intercept) , GALMED, CONATUS OCTETA, SHIRE , reading this site is a good option.

if PPAR potential is not clear for readers,  it would be interesting to look at the poster to be presented at the AASLD in november 2016, published by some of the most competent NASH specialists in USA,  they look to believe in the potential of  PPAR agonists (alpha delta).

In Hepatology, another poster abstract is also enhancing the promising effect on NASH of PPAR delta MXB-8025 from CymaBay therapeutics.. 

PPAR alpha, delta and gamma seems as promising as FXR agonists for future NASH treatment.

So,it seems impossible to me to publish an article on NASH in 2016 with no any mention of PPAR agonists therapeutic pathway.

Until correction , this article is a good candidate to be pinned in the NASH publications 'Hall of Shame'.


Akiva FELT from Oppenheimer is pinned for a brilliant analyse on NASH competitors 


"The analyst views Gilead’s drug wich sould have data from the NASH and cirrohtic NASH trials in Q4, as the most advanced competitive therapy to Intercept’s Obeticholic acid.. »

Oppenheimer Analyst  must change his glasses 

GILEAD Study should have data from its Phase 2b in Q4 2016, It means they will not able,at the best , to start a phase 3 before Q3 / Q4 2017, which mean some phase 3 intermediary results not before 2020, and maybe a subpart H Agreement in 2021 ..

1 - GENFIT plan to be on the NASH market in 2019 .. GILEAD ine 2021.. who is the most advanced ?

2 - Simtuzumab is not targeting NASH disease but cirrhosis and advanced fibrosis induced by NASH .. it seems easy at Oppeinheimer to compare carrots and apples, not for me !

3 - Due to their Phase III design, far more heavy than the GENFIT one, ICPT is more likely to reach the NASH market after GENFIT.

To have a look on real data’s on NASH competitors you can start here

Or take the updated list here


The website BIDNESS ETC is pinned for a second time on the hall of shame for a full off errors article on GILEAD and Intercept 

Error N°1  :

"One of its most promising drug candidates is simtuzumab, a monoclonal antibody for the treatment of hepatic non-alcoholic steatohepatitis (NASH), a non-alcoholic fatty liver disease (NAFLD) affecting 2-5% of all Americans. »

Before writing, they could check the target of Simtuzumab..

Simtuzumab is not targeting the treatment of NASH but the treatment of cirrhosis and advanced fibrosis induced by NASH . they target one of the consequences of  the disease, not the disease ..

Error N°2 :

"However, note that Gilead has a strong competitor aiming for the NASH market. Intercept Pharmaceuticals Inc.'s (NASDAQ:ICPT) lead drug candidate, obeticholic acid (OCA), has completed two successful Phase 2 trials in NASH and NAFLD. »

INTERCEPT is not the leader in the NASH market race for months, Genfit took the lead with their very favorable Phase 3 design.

 And Intercept never completed two successful Phase 2 trial in NASH, 

  • The first Phase 3 study on OCA in NASH  was FLINT which showed some NAS score and fibrosis improvements but never reached the FDA required endpoint in the incoming phases 3 : "Reversion of NASH without worsening of fibrosis"
  • The second one was conducted by Sumitomo which was a complete failure : no any improvement in fibrosis , no reversion on all doses , and a small improvement on NAS score only for the higher 40 mg dose, balanced by an heavy prurit (50%)

Next time you want to publish on NASH .. take the time to read this site before !!!


The website BIDNESS ETC is now pinned on the hall of shame for a surrealist article on Shire and Intercept 

The small paragraph below is a pure delirium

«  By the end of 2015, shares of Intercept Pharmaceuticals surged 17% on reports that Shire could be a potential suitor. Intercept, a $4 billion company, has a lead candidate drug obeticholic acid (OCA), which is close to becoming the first ever treatment option for non-alcoholic fatty liver diseases (NAFLD), including NASH, a condition affecting nearly 5% of the total US population. Intercept is currently Shire’s main rival in the NASH treatment market. Intercept is also developing treatments for other chronic liver diseases, which could serve as a golden entry ticket for Shire in the liver disease treatment market. »

BIDNESS ETC readers should know that Shire  is not active on the NASH treatment market and Intercept, which do not lead anymore in the NASH treatment race, cannot be the Shires’s main Rival. 

The Intercept’s main rival in NASH is Genfit ($GNFTF)

If you want to have updated data on the nash market and actors , you’ll better have to go there 


The article published by Transparancy Market Research was corrected.. and so removed from the hall of shame


 Cowen analyst Ritu Baral note published the 18 of november 2015

«  Ms Baral also noted that competitor GenFit will be starting a Phase 3 trial for GFT505, a competing pipeline drug. The design of the study is similar to that of Intercept’s Regenerate trial, though the analyst is “surprised by the study’s one dose design given the primary endpoint miss in GOLDEN.” In the GOLDEN trial, GenFit’s drug did not show significant improvement in the primary NASH resolution endpoint. She adds, “We also note that this trial is generally smaller than REGENERATE, although final trial details and powering is still tbd.”  » 

  • 1-   So Ms Baral declares herself «  “surprised by the study’s one dose design given the primary endpoint miss in GOLDEN.” In the GOLDEN trial, GenFit’s drug did not show significant improvement in the primary NASH resolution endpoint »

Maybe Ms BARAL was on the north pole for month or was unable to read the presentations relayed by the world best known spécialists of NASH during the last AASDL meeting in SF.

She probabely missed the evolution of the consensual definition of NASH supported by the KOL’s and the FDA. 

This new definition of reversion was applied to GOLDEN datas and the new consensual criteria show a significant statistical reversion of NASH, this was presented by an US NASH specialist the Dr Sanyal in plenary presidential session of AASLD.  To him,  the 120 mg dose of the GENFIT Phase 3 seems accurate.

Two days before Ms Baral financial advice the Professor Arun Sanyal, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, commented: “The Phase 2b GOLDEN-505 study demonstrated that, in patients with clearly established NASH with high disease activity, Elafibranor safely led to resolution of steatohepatitis as well as improvement in cardiometabolic risk factors. Of particular importance is the efficacy of Elafibranor on the new consensual definition of resolution of NASH without worsening of fibrosis. Using this new consensual definition which emphasizes the role of cell injury and inflammation as the main drivers of fibrosis evolution, the GOLDEN-505 trial demonstrated that Elafibranor-treated patients who cleared their NASH also experienced a significant reduction in liver fibrosis. Thus, the design of the Phase 3 trial is optimal to confirm the good efficacy/safety ratio of Elafibranor on resolution of NASH at an interim analysis after 72 weeks, and on prevention of cirrhosis in the long-term.” 

But Ms Barad neglected to read it or decided to hide the fact ?.

  • 2- Ms Baral declared also “We also note that this trial is generally smaller than REGENERATE, although final trial details and powering is still tbd.

Dishonesty or incompetence .. my heart balances … Ms Baral well noticed that the GENFIT study is 'one dose designed' so with two arms ( one placebo and one 120mg/day of Elafibranor) on 1800 patients.

I hope that, covering INTERCEPT PHARMACEUTICAL, she noticed the 3 arms design of their Phase 3 (10 mg/day of OCA, 24 mg/ day of OCA, placebo) on 2000 patients.

I hope so that, as a good scientist , she knows what is an arithmetical  division ?

if you divide the 1800 patients of GENFIT P3 study by the number of arms of the study (2) you’ll obtain 900 patients per arm.

if you divide the 2000 patients of INTERCEPT «  REGENERATE » P3 study by the number of arms of the study (3) you’ll obtain 666 patients per arm.

In Facts GENFIT explained that the arms would be unbalanced -

2 elafibranor : 1 placebo

It means that the Elafibranor arm will screen 1200 patients to compare with each OCA arms (666)

The number of patients par arms in the GENFIT Study is 35% bigger than in the REGENERATE study and the final trials details will be a lot better for GENFIT study than INTERCEPT study .

Ms Baral assertion on a GENFIT trial generally smaller than REGENERATE is a big mistake or a big lie, depending your opinion on the misleading or not of this analyse.

It is maybe time to explain to this senior 'biotech Analysts’ that, before writing false or biased informations on a company, it would be better to have a look on specialist's advices (maybe Ms Baral finds herself more competent, I am interested to examine all the publications she produced on the subject) and maybe to follow the consensual evolutions supported by the FDA.


coming soon : another analyst misleading note



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