How Lanifibranor works
The hallmark of scleroderma (also known as systemic sclerosis) is widespread tissue scarring and thickening, a phenomenon known as fibrosis.
The exact trigger for this fibrosis is not known, but proteins called perioxisome proliferator-activated receptors (PPARs) are thought to play a role. PPARs belong to a family of transcription factors (protein that can control the activity of genes) that are able to act directly on fibrosis-related genes. There are three known subtypes of PPAR receptors: alpha (α), gamma (γ), and delta (δ).
Lanifibranor is a pan-PPAR receptor agonist, meaning that it works by increasing the effects of all three PPAR receptors. It is hoped that by acting on all PPAR receptor subtypes, Lanifibrinor will be more effective in reducing fibrosis than PPAR receptors that only act on one receptor subtype.
Lanifobranor in clinical trials
Lanifibranor showed good tolerability, safety, and efficacy in Phase 1 and 2a studies in healthy volunteers and type 2 diabetic patients. The treatment’s anti-fibrotic efficacy was also demonstrated in in vitro and in vivo preclinical studies, with Lanifibranor inducing the regression of pre-existing fibrotic damage in the liver and in the skin, and preventing the further development of fibrosis.
A Phase 2b proof-of-concept study (NCT02503644), called FASST, is now underway in 145 patients with diffuse cutaneous systemic sclerosis at sites in 10 European countries. This randomized and double-blind study’s objective is to compare two doses of oral Lanifibranor (400 mg and 600 mg capsules, given twice daily) against placebo over 48 weeks of treatment. During this time, assessments will be made to monitor the treatment’s efficacy and safety, with a primary goal — change in measures of skin thickness — determined by the Modified Rodnan Skin Score (MRSS).
Top-line results from the trial are expected in early 2019. The FASST study is being led by Professor Yannick Allanore at the Hôpital Cochin in Paris and Professor Chris Denton at University College London.
Lanifibranor received orphan designation for the treatment of scleroderma from both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The company’s clinical development plan has been validated by the EMA and the treatment has recently received a positive review by the Data Safety Monitoring Board (DSMB).
Lanafibranor is also undergoing a Phase 2b clinical trial (NCT03008070), called NATIVE, investigating its efficacy in patients with NASH, a chronic liver disease.
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