2018,  THE NASH LANDSCAPE


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April 2018, what is the updated NASH landscape ?



§ OCALIVA (INTERCEPT) :

This drug suffered from a bad start in PBC, the agreement of the drug by the FDA was not obvious and it seems that patients associations pushed hard to obtain it. Last September a warning was published by the FDA after 21 deaths of patients under treatment. For many of the fatal events, link with the treatment could not be established but FDA regards some with suspicion.

At the end of 2017, the number of deaths raised to 63. FDA asked for a ‘blackbox' warning on the OCALIVA package but with limited restrictions. 

To my opinion, it is difficult to assess is the degree of risk carried by OCALIVA treatment for PBC patients because they are mainly in bad condition with a bad pronostic therefore some deaths are likely to occur. We need more analysis to estimate the actual risk.

Nevertheless, the bad safety profile of the drug seems confirmed. To me, it should withdraw OCALIVA from the list of potential 'backbone' treatments of NASH ( and also because of the induced prurit which reduces the compliance of the treatment)

The Phase 3 trial recruitment for interim results was reduced by Intercept from 1400 patients to 750 patient one year ago (ie early 2017). But two months ago (ie in November 2017), the total amounts of patients to recruit in the trial has been changed from 2000 patients to 2350 patients with no further explanations. To date we don’t know whether this change will have any impact (or not) on the interim trial result timeframe. 

OCALIVA is classified by NashBiotechs.com as possible treatment complementary to another 'backbone' treatment.


§  ELAFIBRANOR (GENFIT) :

No bad news for Elafibranor, the DSMB supported the pursuing of the trial: no safety problem has been detected. The interim result recruitment of 1000 patients is supposed be completed by end of T1 2018.

If the positive results of Phase 2b are confirmed in Phase 3, ELAFIBRANOR might become the first backbone treatment for NASH on the market by 2021.

ELAFIBRANOR is classified by NashBiotechs.com as possible NASH ‘backbone' treatment.

GENFIT's biomarker diagnosis programm is the key for a fast growing market !

 

§  GR-MD-02 (GALECTIN)

The published results of the Ph2b were not good at first reading: the primary endpoint has not been reached and I was negative on the future of the compound. However,after an attentive reading of data's published , I changed my mind. 

Actually, GR-MD-02 got some good results, reducing portal pressure on cirrhotic patients without varices.  It means that they can target a lucrative market, about 50% of cirrhotic patients (NASH or other induced diseases). If those results are confirmed by a Phase 3, GR-MD-02 might become a blockbuster on cirrhosis. 

GALECTIN announced that they will start discussions soon with FDA to launch a Phase 3 in cirrhosis.

GR-MD-02 is classified by NashBiotechs.com as possible treatment complementary to another backbone treatment.

 

§  MGL-3196 (MADRIGAL)

Madrigal published interim results at the end of 2017. Those good results were only on liver fat reduction. They were a little bit better than the GILEAD GD0976’s results on that point. One has to wait for Q2 2018 to see if fat reduction is associated with NASH resolution and fibrosis improvement. If it is the case, and if the results are confirmed by a future phase 3, MGL-3196 could become a backbone treatment for NASH on the market by 2025. A presentation is planned on April 13 at EASL.

MGL-3196 is classified by NashBiotechs.com as possible backbone treatment.

 

§  SELONSERTIB (GILEAD)

Selonsertib potential is mainly based on expectations because the phase 2 used as reference to claim its antifibrotic potential is far from academic, with a very small amount of patients and no trustworthy placebo (Simtuzumab was used as placebo by default).

GILEAD decided to push their luck a bit and to push forward directly a Phase 3 with a short duration (11 months). I doubt that it will work, because their compound is an ASK1 reducing globally apoptosis of cells in the body and some specialists seem concerned by a possible cancerigen-induced effect. So, if they get some good results on fibrosis in 11 months, the delay would be too short to evaluate a possible cancerigen adverse effect, and regulation agencies could ask for more time before giving any agreement.

To my opinion the short duration of their trial jeopardizes a possible subpart H. In this case, the drug access to the market could be postponed by 2 years.

SELONSERTIB is classified by NashBiotechs.com as possible complementary treatment to another backbone treatment.

 

§  IMM124E (IMMURON)

Last Immuron interim results of Phase 2 showed mainly nothing, no real difference with placebo. Last results published in March 2018 show improvements for LPS and CK18 serum levels  but only on a sub group of patients, the primary and seconday endpoints are not reached on ITT population.

Detailled analysis of IMM-124E results by NASHBIOTECHS is here

It is not sure that they have a future on the NASH market. Waiting for the complete results and the publication to confirm this point of view.

IMM124E is classified by NashBiotechs.com as possible backbone treatment.


§  EMRICASAN (CONATUS)

Apr-4-2018  Conatus annonced results from Phase 2b POLT-HCV-SVR Clinical Trial, this trial was not targeting NASH but liver transplanted patients with residual fibrosis or cirrhosis. The primary Endpoint on fibrosis improvement was not reached on ITT population but the trial show some improvements on a small sub population. 

It is difficult to see if those results prefigures the results expected on NASH population in ENCORE -PH, ENCORE-NF and ENCORE-LF trials, but they are not encouraging !

ENCORE -PH results are expected H2 2018

ENCORE-NF results are expected Q1 2019

ENCORE-NF results are expected H2 2019

EMRICASAN is classified by NashBiotechs.com as possible complementary treatment to another backbone treatment.


§  CENICRIVIROC (ALLERGAN)

Last results of CENICRIVIROC Ph2 trial at 2 years  are not good at all ! All noticed benefits on fibrosis at one year, disappeared at two years. 

With humor, we can bet on a one year treatment!  No many chances to reach the market!  We have to wait for the Ph 3 results to make an opinion.

CENICRIVIROC is classified by NashBiotechs.com as possible complementary treatment to another backbone treatment.


§  ARAMCHOL (GALMED)

Results of ARRIVE Ph 2a (evaluated the safety and efficacy of Aramchol™ at 600mg/day versus placebo in 50 patients with HIV-associated lipodystrophy and non-alcoholic fatty liver disease) were published the Feb 14 2018 and the primary endpoint ( improvement of liver fat at 12 weeks, as measured by MRI-PDFF) was not reached !

Results of ARREST (phase 2b  study with 248 NASH patients assessing Aramchol™ 400 and 600mg/day following 52 weeks treatment, with endpoints measured by MRS and liver biopsies)   are expected Q2 2018. 

If results are good and confirmed by a phase 3, ARAMCHOL could become a backbone treatment for NASH on the market by 2024.

ARAMCHOL is classified by NashBiotechs.com as possible backbone treatment.


Except an hypothetic fast approval of the selonsertib, only two drugs could dominate the market from 2020 to 2025, OCALIVA and ELAFIBRANOR. 

As ELAFIBRANOR is supposed to be a backbone treatment and OCALIVA a complementary treatment, they will not be in real competition. 

It is interesting to see that both GENFIT and INTERCEPT will present positive data’s on OCA and ELAFIBRANOR combo studies at EASL 2018.



to follow …  the (almost) full list of compounds targeting NASH is HERE and a free forecast market survey is HERE



G Divry

Notice that I am neither a physician nor a biologist, my point of view is only that of an enlightened amateur, so it must be taken for what it is, a questionable point of view


Thanks to Julian for its useful English reading and corrections !



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