ARAMCHOL RESULTS QUICK ANALYSIS


Corrected because of an initial misreading of 400mg results

The figures provided by GALMED in their communicate are not very detailled, so this quick analysis will be completed as soon more data will be available.

To be complete one should know that patients  baselines in GALMED trial were differents from the other known trial to compare with

Mainly, patients recruited had :

  1. Liver fat concentration in the liver of 5.5% or more as measured by NMRS.
  2. Known type II Diabetes Mellitus or pre-Diabetes 


  • 30% of patients had a NAS  score =4
  • 70% of patients had a NAS  score >=5


  • 60% of patients has a F2 or F3 fibrosis grade


Data provided on fat reduction are mesured by NMRS and provided in absolute, it mean that we'll need the absolute Liver fat concentration at baseline to estimate the  improvement in percentage as provided one week ago by MADRIGAL.


The design published in clinicaltrial.gov announced  240 patients in 3 arms.  247 patients were recruited and data are published to date on 214 patients, we dont know if data are published on ITT or PP population


We will concentrate our analysis on consensual NASH trials endpoints and on results statistically significant ( p<=0,05)

BUT I FOUND NONE !


NASH reversion without worsening of fibrosis

We can compare the NASH reversion endpoint with the two other phases 2b trial published using the same endpoint. 

because of strong differences in baselines caracteristics between trials, to compare similar populations we should use post analysis of GOLDEN and FLINT trials,  including balanced centers as they designed their Phase 3

FLINT definition of NASH reversion was not defined at start but in a post hoc study they applied the new definition on a sub group of patients with well-defined steatohepatitis at baseline. 

Because of that we will compare  here the figures based on PP populations and not ITT populations.


Results of NASH reversion according to new definition. Drug result vs placebo results


ARAMCHOL 600 mg     16,5%  vs   5%     RR= 3,3  non significant

MGL 3196                  27%  vs    6%    RR = 4,50

OCA                            19%  vs    8%     RR = 2,37

ELAFIBRANOR*     26%  vs    5%     RR = 5,20

*  3 arms centers as defined in Ph3 protocol 

 Aramchol 600mg result is considered NOT significant because p>0,05 (not far from it p =0,0514) 

Looking at the Relative Ratio values, one can see that ARAMCHOL is below main other compounds in terms of efficacy.

On ITT population, the figures should be ( estimation)

ARAMCHOL 600 mg     13 %  vs   4,3%     RR= 3,02  non significant


NASH improvement of fibrosis without worsening of NASH

Regarding this endpoint the results of the both doses of ARAMCHOL , 400mg and 600 mg are clearly not stastistically significatives (p= 0.8425 and p = 0.2110) as were the results of MGL3196 a week ago!

As in MGL3196 trial the spontaneous fibrosis reduction in placebo arm is high !  this is surprising !  


NAS Score reduction

We can't compare the NAS Score reduction by 2 pts with the  other phase 2b trial because GALMED did not provide the results on that protocol defined secondary endpoint, just telling us that results were not stastistically significatives (p>0,05) another miss !


Conclusion

Result on all population is far from good, no  consensual NASH endpoint results are statistically significant, it is a global miss, and MRS fat mesures are difficult to read with a reverse dose response effect!  

But, as usual in NASH trials, nothing is black and white and it will take time to isolate sub groups of NASH patients, responding statistically to ARAMCHOL in a way  to prepare a phase 3 design FDA compatible.




G Divry

Notice that I am neither a physician nor a biologist or financial analyst, 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


Annexe : published  data’s 

ARAMCHOL




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