LAU-7b for Lung Inflammation in Cystic Fibrosis

LAU-7b is an oral form of the retinoid fenretinide, being developed by Laurent Pharmaceuticals. Retinoids are a group of compounds related to vitamin A. Fenretinide may help reduce the inflammatory response in the lungs of people with cystic fibrosis (CF).1 Administrated as a once-a-day, solid dose of fenretinide, LAU-7b is designed to correct the defective metabolism and modulate chronic inflammation due to the genetic defect that causes cystic fibrosis.2

How LAU-7b works

Arachidonic acid (AA) and docosahexanoic acid (DHA) are two essential fatty acids that play a key role in maintaining an effective immune-inflammatory response. The genetic defect that causes CF leads to exaggerated AA-mediated inflammation and low DHA-mediated resolution, causing lung infection and local tissue damage.

LAU-7b works by correcting the defective metabolism of AA and DHA, and controlling chronic inflammation via what the company’s calls “a pro-resolving mechanism” maintained by a relation to the expression of the CF genetic defect.

Resolution of inflammation is a new approach that uses the body’s own ability to modulate inflammatory responses, with the goal of addressing inflammation without inducing immunosuppression.

LAU-7b studies

LAU-7b was tested in people with cystic fibrosis in a dose-ascending Phase 1b (NCT02141958) trial, and demonstrated good safety and tolerability, as well as promising pharmacokinetic and pharmacodynamic properties.

The trial was a single-center, double-blind, and placebo-controlled study  of three increasing oral doses of LAU-7b compared to placebo. Treatment with up to 300 mg of LAU-7b for 21 days was found to be safe and well-tolerated by adults with CF, and achieved the proposed target plasma concentration in all participants at that dose level. LAU-7b normalized the blood levels of AA and DHA in almost all of the participants, leading to a more anti-inflammatory pattern in the patients, especially during pulmonary exacerbation, Laurent reported on its website.

A Phase 2 study in adults with CF, using the 300 mg dose level, is currently being prepared for the United States and Canada.4

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