Laurent Pharmaceuticals Initiates Phase 1 Clinical Study Of “Orphan Drug” Fenretinide in Cystic Fibrosis

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by Charles Moore |

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Montreal-based biotech startup Laurent Pharmaceuticals Inc. announced Wednesday that the Research Institute of the McGill University Health Centre (RI-MUHC) in Montreal has begun enrolling patients in an investigator-initiated clinical trial evaluating the safety, tolerability and pharmacokinetics of a novel oral formulation of Fenretinide in adult subjects with Cystic Fibrosis (CF) and Pseudomonas aeruginosa lung colonization.

The study will be conducted at the Montreal Chest Institute at the MUHC in Montréal, with financial support from McGill University, MSBi Valorisation and Laurent Pharmaceuticals.

The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and health-care hospital research centre. Research is organized by eleven research axes (or programs). Located in Montreal, Quebec, Canada, the Institute is the research arm of the McGill University Health Centre affiliated with the Faculty of Medicine at McGill University.


This initiation of clinical development follows years of extensive preclinical research conducted at RI-MUHC, showing that oral administration of Fenretinide, a vitamin A derivative, corrects the lipid imbalance in lungs and plasma of specific animal models of CF, resulting in reduced lung inflammation and dramatic decrease in the severity of pulmonary infections with Pseudomonas aeruginosa, a bacterium involved in perpetuating the inflammation-infection vicious cycle in CF. Pseudomonas aeruginosa is the main cause for difficult-to-treat chronic infection in CF, and is associated with lung insufficiency and reduced survival.

The Phase 1 trial, entitled “Safety Study of Fenretinide in Adult Patients With Cystic Fibrosis” is a randomized, double-blind, placebo controlled, intra-patient dose-escalation clinical trial that will enroll a minimum of 16 adult CF patients chronically infected with Pseudomonas aeruginosa.

Fenretinide will be administrated orally as 100 mg capsules, one dose per day for 21 consecutive days, in up to three treatment cycles of ascending doses, with a minimum of 7-day drug-free period between cycles. Twelve (12) patients will be on Fenretinide.

The primary objective is to establish the safety and tolerability of a once a day regimen of Fenretinide oral capsules. More information about the trial can be found at: Search for: NCT02141958. The study is currently recruiting participants.

The study outline provided by McGill University Health Center notes that patients with cystic fibrosis have an innate imbalance of essential fatty acids, with increased arachidonic acid (AA) levels, decreased docosahexanoic acid (DHA) levels, and elevated AA/DHA ratio. An increasing amount of evidence suggests that this lipid imbalance is a primary effect in CF, playing a major role in the infection-inflammation vicious cycle that leads to respiratory failure. Fenretinide, a derivative of vitamin A, was shown to correct the AA/DHA imbalance in lungs and blood plasma in specific animal model of CF, resulting in reduced lung inflammation and decrease in the severity of pulmonary infections with Pseudomonas aeruginosa.

The Research Institute of the McGill University Health Centre (RI-MUHC) is a world-renowned biomedical and hospital research centre. Located in Montreal, Quebec, the Institute is the research arm of the McGill University Health Centre affiliated with the Faculty of Medicine at McGill University. The Research Institute offers a dynamic multidisciplinary research environment that fosters collaboration and leverages discovery aimed at improving the health of individual patients across their lifespan.

The RI-MUHC was built to facilitate investigator-initiated and discovery-driven research that creates new knowledge in healthcare research along the whole spectrum of investigative activities. This involves fundamental biomedical research, patient-oriented and applied clinical research, research on health services and health systems, as well as population and health promotion research, including societal and cultural effects on health.

MSBi Valorisation (MSBiV) is an early stage group that provides capital, manpower and business sense to monetize promising technologies developed within McGill University, Université de Sherbrooke and Bishop’s University and their affiliated research centres. The company is instrumental for creating spin-offs as well as technology opportunities ready to be licensed to existing companies.

On April 23, 2013, MSBi Valorisation announced the creation of Laurent Pharmaceuticals, a new, private, biopharmaceutical company specializing in in drug development for orphan diseases.

Laurent has a lead program focusing on Fenretinide, an intensively explored but never commercialized synthetic retinoid derivative, as novel therapy for Cystic Fibrosis (CF) patients suffering from lung infection with Pseudomonas aeruginosa.

RadziochDThe research involving Fenretinide in CF was led by Dr. Danuta Radzioch, Professor at the Departments of Medicine and Human Genetics at McGill’s Faculty of Medicine, and received financial support from the Quebec’s Ministère de l’Enseignement supérieur, de la Recherche, de la Science et de la Technologie (MESRST), the Canadian Institutes of Health Research (CIHR), and MSBiV. Dr. Radzioch and her team demonstrated that Fenretinide corrects the AA/DHA lipid imbalance in lungs and plasma of CftrKO mice, resulting in reduced lung inflammation as well as the frequency and severity of lung infections from Pseudomonas aeruginosa, the bacteria responsible for excessive lung inflammation and the primary cause of mortality in CF.

“These data confirm the increasing amount of evidence suggesting that the fatty acid imbalance is part of the pathogenic mechanism by which the defective gene leads to the symptoms in CF patients, and not a reflection of the disease manifestations”, said Dr. Radzioch, who is also a researcher with the RI-MUHC. “I am really excited to continue the development of this extremely interesting technology in the context of the newly created Laurent Pharmaceuticals”.

In 2010, the U.S. Food and Drug Administration granted McGill the “Orphan Drug Designation” for the use of the drug Fenretinide for the treatment of pulmonary infections caused by Pseudomonas aeruginosa in patients with Cystic Fibrosis (CF). McGill and Laurent plan to start a Phase I clinical trial in adult CF patients by the end of 2013.

“The concept of using Fenretinide in CF has the potential to become an important disease-modifying oral treatment in a market dominated by symptomatic inhalation therapies. I’m very pleased with the support received from MSBiV and its academic partners in the creation of this start-up as the commercialization vehicle for the technology developed by Dr. Radzioch and her team”, says Dr. Radu Pislariu, MD, President and CEO of Laurent Pharmaceuticals. “The once-neglected field of rare diseases is now gaining increasing attention from the pharmaceutical industry and I’m confident that Laurent is well positioned to establish a strong presence in this sector.”

LARoseAM“MSBi Valorisation is excited to be part of this entrepreneurship initiative, which is at the core of our business model”, says Dr. Anne-Marie Larose, the President and General Manager of MSBiV. “We have been long-time supporters of the technology developed by Dr. Radzioch and her team, constantly helping through our expertise and network, and we are eager to continue in providing our support and added value to Laurent, which we strongly believe is on its way to becoming a valorisation success here in Quebec”.
Laurent Pharmaceuticals
MSBi Valorisation
The Research Institute of the McGill University Health Centre (RI-MUHC)

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