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Lanifibranor in NASH – a Pan-PPAR Agonist

Lanifibranor in NASH

lanifibranor in nash

Lanifibranor is a novel drug from the class of medicines called PPAR (Peroxisome
proliferator-activated receptors) agonists. Lanifibranor regulates the three cardinal processes involved in the pathogenesis of NASH (Non-alcoholic steatohepatitis). These are:

  • Inflammation
  • Fibrogenesis, and 
  • Metabolism

Lanifibranor regulates these functions by acting on nuclear receptors. It is a PAN-PPAR agonist and is considered to be more effective than single or dual PPAR agonists. 

Currently, the three different PPAR agonists that are being studied in the treatment of various metabolic diseases are:

  • PPAR alpha,
  • PPAR gamma, and
  • PPAR delta

These three PPAR agonists act on different receptors. The Pan-PPAR agonists are drugs that activate all three receptors and hence are considered more effective in reducing the expression of genes involved in inflammation and liver fibrosis.

Different drugs that act on the PPAR receptors are given in the table below:

 

Target Peroxisome Proliferator-activated Receptors

Drugs

Alpha

Gamma

Delta

Elafibranor & Lanifibranor

Yes

Yes

Yes

Muraglitazar

Yes

Yes

No

Lobeglitazone

No

Yes

No

Naviglitazar

No

Yes

No

Fibrates (Gemfibrozil, Fenofibrate etc)

Yes

No

No

Thiazolidenediones (Pioglitazone & Rosiglitazone)

No

Yes

No

Diabetes Medicines that Cause Weight Gain

Lanifibranor in NASH (Non-alcoholic steatohepatitis):

A recent trial published in the NEJM evaluated the effectiveness of Lanifibranor in the treatment of NASH (Non-alcoholic steatohepatitis) [Ref]. 

247 patients with moderately severe NASH were enrolled in the study in a 1:1:1 ratio. Patients either receive Linafibranor in a dose of 1200 mg or 800 mg, or a placebo medicine.

The primary outcome was a minimum of two-point reduction in the SAF-A score without worsening of fibrosis. More patients in the high-dose Lanifibranor group achieved the primary outcome compared to placebo.

Primary Outcome

Reduction in 2 points SAF-A score without worsening of fibrosis

Lanifibanor 1200 mg

55%

0.007

Lanifibranor 800 mg

48%

0.07

Placebo

33%

 

Table:1

Secondary Outcomes:

Outcome

Resolution of NASH without worsening of fibrosis

Lanifibanor 1200 mg

49%

Risk Ratio vs placebo: 2.2

Lanifibranor 800 mg

39%

Risk Ratio vs placebo: 1.7

Placebo

22%

 

Table 2

Outcome

Improvement in fibrosis of at least 1 stage worsening of NASH

Lanifibanor 1200 mg

48%

Risk Ratio vs placebo: 1.7

Lanifibranor 800 mg

34%

Risk Ratio vs placebo: 1.2

Placebo

29%

 

Table 3

Outcome

Resolution of NASH plus improvement in fibrosis stage of at least 1

Lanifibanor 1200 mg

35%

Risk Ratio vs placebo: 4

Lanifibranor 800 mg

25%

Risk Ratio vs placebo: 2.6

Placebo

9%

 

Table 4

Among patients treated with Lanifibranor, weight gain and peripheral edema occurred more frequently compared to placebo. Gastrointestinal side effects were also more common in the treatment group.

The levels of plasma adiponectin were elevated corresponding to the degree of weight gain. There was also an improvement in the lipid profile. Patients in the treatment groups had lower triglycerides and high levels of HDL (high-density lipoproteins) compared to placebo. Glycated hemoglobin improved by 0.4% each in the treatment group vs 0.1% in the placebo groups.

In Conclusion:

Lanifibranor, a Pan-PPAR agonist, when administered in a dose of 1200 mg once daily results in a significant improvement in the active NASH compared to placebo.

What do you think?

Written by Diabetes Doctor

I am an Internist practicing medicine for the last fifteen years. Over the years, I have learned that medicine is not about prescribing pills. True medical practice is helping people.
I do prescribe pills as well but the best results I get are when I motivate people to overcome their problems with little changes in their lifestyles.
Since most of my patients are obese, have diabetes, hypertension, high cholesterol levels, I am writing at dibesity.com when free.
Dibesity, I know the correct word is diabesity. Ignore this! Be with us.

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