IMMURON - INTERIM ANALYSIS RESULTS - ??? UPDATED

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JULY 2017 ANNOUNCEMENT

MELBOURNE, Australia, July 10, 2017 (GLOBE NEWSWIRE) -- Australian biopharmaceutical company, Immuron Limited (ASX: IMC) (NASDAQ: IMRN), is pleased to announce safety and efficacy results of the interim analysis of its ongoing IMM-124E Phase II study in NASH.  The objectives of this analysis was to establish the safety of the compound and to provide a preliminary read on efficacy signals.

The NASH Phase II trial has enrolled 133 patients with the top-line results expected in 4Q2017.  The pre-planned analysis was triggered when 80 subjects completed treatment.

The demographics of the population analyzed in the interim analysis were balanced in all three groups (placebo, low dose -600mg- and high dose -1200mg-) including sex, race, age, height, weight, BMIs, HbA1c and baseline hepatic fat fraction (HFF). 

Highlights from the interim analysis are as follows:

  • IMM-124E was safe and there were no safety signals when compared to placebo.
  • The treatment was well tolerated and no subjects discontinued therapy due to side effects.
  • The IMM-124E 1200mg and  600mg groups, as well as the placebo group, all demonstrated a significant change of ALT at 24 weeks compared to baseline (p=0.0038, p=0.016 and p=0.0337).  However, no statistical difference was noted between the groups.
  • When accounting for all ALT values thoughout the study period, the area under the curve (AUC) was calculated, and when correcting for ALT baseline values (using ANCOVA), a trend (p=0.067) in improvement in ALT was noted in the 1200 mg group when compared to placebo 
  • When using the predicted ALT-AUC values, the overall AUC for ALT was statistically significantly lower for the 1200mg and 600mg groups (p=0.0036 and p=0.0075, respectively) when compared to placebo. 
  • The overall AUC for AST values, when corrected for baseline values, was also significantly lower in the 1200mg and 600mg dose groups (p=0.0036 and p=0.0098, respectively) when compared to placebo.
  • There was no evidence of systemic absorption of IMM-124E as assessed by circulating bovine immunoglobulin.
  • At the time of this interim analysis, no difference was noted in the hepatic fat fraction (HFF), which is  the study’s primary endpoint between the groups.  This is most likely attributable to the small sample size in this analysis.

Based on the results of the interim analysis, IMM-124E has demonstrated to be a non-absorbable, safe and tolerable compound in patients with NASH.  Early biochemical improvements in liver enzymes are noted, suggesting potential therapeutic benefit for treatment of NASH.  The DSMB recommendation was to continue the trial to completion, as there is no concern for safety or futility.


NASHBIOTECH INITIAL COMMENT ( AUG 2017)

Comments dones in august 2017

IMM124E is safe .. OK  

but no any action on ALT or fat in the liver was noted!  even the supposed improvement mentionned vs placebo after retreatment is not statistically pertinent. 

Nothing !

The good news is, at mid stage of the trial,  IMM 124E has no action on nothing , but it seems very safe and the paediatric trial initiated months ago can continue.  

Not sure that childs will benefit from the product, but it is safe !!

The bad news is, the IMM124 effect on NASH and even NAFLD seems null,  and patients would need to find another way to cure their disease !


MARCH 2018 ANNOUNCEMENT

SUMMARY: IMM-124E Clinical Trial Results

IMMURON PRESENTATION 

  • IMM-124E demonstrated good safety and tolerability on both doses
  • A statistically significant effect of IMM-124E to reduce serum levels of LPS
  • A statistically significant and clinically meaningful effect to reduce ALT levels by 30% or more in patients with elevated ALT at enrollment
  • Statistically significant reduction in mean AST compared to placebo.
  • Statistically significant effect to reduce CK-18 compared to placebo
  • IMM-124E was shown to remain in the gut and not cross into the bloodstream
  • No effect on liver steatosis 


NASHBIOTECH COMMENT ( UPDATED MARCH 2018)


IMM124E is still safe .. OK  

IMMURON enhance their results on LPS, AST and CK-18.

but if you look at their study design

FIRST YOU SHOULD NOTICE THAT DATA PUBLISHED ARE NOT DONE ON ITT POPULATION BUT ON BALANCED SITES (94 patients),  30% ot patients are excluded and no data is provided on ITT population( 133 patients). 

Only steatosis data are based on PP population (102 patients)


Primary Outcome Measures  :

  1. Body Temperature [ Time Frame: 24 Weeks ]

Changes in body temperature   NO DATA 

Percentage Fat Content of the Liver [ Time Frame: 24 Weeks ] 

Mean change from Baseline in Percentage Fat Content of the Liver measured by Magnetic Resonance Imaging (MRI) at Week 24 NOT REACHED ON PP Population

Adverse Events [ Time Frame: 24 weeks ]

Number of patients with adverse events OK DATA 

Adverse Events [ Time Frame: 24 weeks ]

Severity of adverse events OK DATA 

Respiratory Rate [ Time Frame: 24 weeks ]

Change in Respiratory Rate   NO DATA 

Pulse Rate [ Time Frame: 24 weeks ]

Change in Pulse Rate  NO DATA 

Systolic Blood Pressure [ Time Frame: 24 weeks ]

Change in Systolic Blood Pressure  NO DATA 

Diastolic Blood Pressure [ Time Frame: 24 weeks ]

Change in Diastolic Blood Pressure  NO DATA 

Hematology, Coagulation, Clinical Chemistry, Serum Lipids, Blood Glucose and Urinalysis [ Time Frame: 24 weeks ]  FEW DATA 

Change in Clinical Laboratory tests (Hematology, Coagulation, Clinical Chemistry, Serum Lipids, Blood Glucose and Urinalysis) FEW DATA 

Serum Alanine Aminotransaminase (ALT) [ Time Frame: 24 weeks ]

Mean change from Baseline in Serum Alanine Aminotransaminase (ALT) at Week 24  NOT REACHED ON ITT POPULATION NOR ON BALANCED SITE !


Secondary Outcome Measures  :

  1. Peak serum concentration (Cmax) [ Time Frame: 0, 4, 12 and 24 Weeks ]

Peak serum concentration (Cmax) of IMM-124E OK DATA 

Minimum serum concentration (Cmin) [ Time Frame: 0, 4, 12 and 24 Weeks ]

Minimum serum concentration (Cmin) of IMM-124E OK DATA 

Area Under the Concentration Time Curve (AUC) [ Time Frame: 0, 4, 12 and 24 Weeks ]

Area Under the Concentration Time Curve (AUC) of IMM-124E OK DATA 

Elimination Half Life (T1/2) [ Time Frame: 0, 4, 12 and 24 Weeks ]

Elimination Half Life (T1/2) of IMM-124E OK DATA 

Body Mass Index (BMI) [ Time Frame: 24 Weeks ]

Change from Baseline of Body Mass Index (BMI) at 24 weeks NO DATA 

Waist Circumference [ Time Frame: 24 Weeks ]

Change from Baseline of Waist Circumference at 24 weeks NO DATA 

Waist:Hip Ratio [ Time Frame: 24 Weeks ]

Change from Baseline of Waist:Hip Ratio at 24 weeks NO DATA 

Hemoglobin (HB)A1C [ Time Frame: 24 Weeks ]

Change from Baseline of Hemoglobin(HB)A1C at 24 weeks NO DATA 

Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: 24 Weeks ]

Change from Baseline of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at 24 weeks NO DATA 

Total Cholesterol [ Time Frame: 24 Weeks ]

Change from Baseline of Total Cholesterol at 24 weeks NO DATA 

Triglycerides [ Time Frame: 24 Weeks ]

Change from Baseline of Triglycerides at 24 weeks NO DATA 

Low density lipoprotein (LDL) [ Time Frame: 24 Weeks ]

Change from Baseline of Low Density Lipoprotein (LDL) at 24 weeks NO DATA 

High Density Lipoprotein (HDL) [ Time Frame: 24 Weeks ]

Change from Baseline of High Density Lipoprotein (HDL) at 24 weeks NO DATA 

Serum Alanine Aminotransaminase (ALT) [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]

Mean change from Baseline of serum ALT  GLOBALLY NOT REACHED ON ITT POPULATION NOR ON BALANCED SITE !

Serum Aspartate Aminotransaminase (AST) [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]

Mean change from Baseline of Serum AST   DECREASE 30% decrease NOT REACHED ON ITT POPULATION NOR ON BALANCED SITE !

Bilirubin [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]

Mean change from Baseline of Bilirubin NO  DATA 

Albumin [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]

Mean change from Baseline of Albumin NO  DATA 

Gamma Glutamyl Transpeptidase (GGT) [ Time Frame: 0, 4, 8, 12, 16, 20 and 24 Weeks ]

Mean change from Baseline of Gamma Glutamyl Transpeptidase (GGT) NO  DATA 

Serum Alanine Aminotransaminase (ALT) [ Time Frame: 24 Weeks ]

Number of patients with ALT within the normal reference range at Week 24(defined a <19 IU/L for women and <30 IU/L for men)  NO  DATA 


Other Outcome Measures:

  1. Inflammatory Cytokines and other markers [ Time Frame: 0, 4, 12 and 24 Weeks ]

Serum Concentrations of Lipopolysaccharide (LPS), C-Reactive Protein (CRP), CK-18 fragments, C-peptide, Adiponectin and Cytokines IL6, IL12, IFN gamma and TNF alpha  POSITIVE ON LPS, CK18  NO DATA ON THE OTHER INDICATORS

Regulatory T cells in Peripheral Blood Mononuclear Cells [ Time Frame: 0, 12 and 24 Weeks ]

Relative levels of Regulatory T cells in Peripheral Blood Mononuclear Cells NO  DATA 

Gut Microbiome from Fecal Samples [ Time Frame: 0, 4, 12 and 24 Weeks ]

Characterization of the gut microbiome from fecal samples by DNA extraction and Bacterial ribosomal DNA amplification and sequencing NO  DATA 

Gastrointestinal LPS levels [ Time Frame: 0, 4, 12 and 24 Weeks ]

Gastrointestinal LPS levels from fecal samples NO  DATA 


CONCLUSIONS

On published results for Primary endpoints 

Percentage Fat Content of the Liver NOT REACHED ON ITT AND PP POPULATION

Serum Alanine Aminotransaminase (ALT) 30% reduction NOT REACHED ON ITT (133) AND PP(102)  POPULATION NOR ON BALANCED SITES (94) BUT ONLY ON SELECTED SUB POPULATION

On Secondary Endpoint  

Mean change from Baseline of serum AST :   30% reduction NOT REACHED ON ITT (133) AND PP(102)  POPULATION NOR ON BALANCED SITES (94) BUT ONLY ON SELECTED SUB POPULATION

On Other Outcome Measures

Serum Concentrations of Lipopolysaccharide (LPS) : IMPROVED (>= 15% decrease) ON BALANCED SITES (94) NO DATA ON ITT AND PP POPULATION 

CK-18 fragments : IMPROVED (>= 15% decrease) ON BALANCED SITES (94) NO DATA ON ITT AND PP POPULATION 


Decrease in LPS and  CK18 where not primary targets of the trial, their decrease can be encouraging but one should notice that it is only on a sub part (70%) of the ITT population.

primary and secondary endpoints published are a failure except the for safety 

To my opinion those new results are well presented but not good by far !




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