- LAU-7b is safe and well tolerated by adult Cystic Fibrosis (CF) patients
- The pharmacokinetic profile fully achieved the protocol dose selection rationale
- Study drug shows a convergence of multiple promising pharmacodynamic trends
MONTREAL, QC, Canada - June 15th, 2015
Laurent Pharmaceuticals Inc. announced today positive topline results from a Phase 1b clinical trial with LAU-7b in adult CF patients. LAU-7b is a novel oral formulation of fenretinide, a synthetic retinoid investigated for its lipid modulating properties and potential to address the aberrant inflammatory response in CF. The study was conducted at the McGill University Health Centre (MUHC). The trial demonstrated that LAU-7b administrated orally in ascending doses up to 300mg, during three cycles of 21 consecutive days, was safe and well tolerated by adult CF patients. The pharmacokinetic profile of LAU-7 fully achieved the targeted blood levels and dose selection rationale. The treatment also normalized the lipid imbalance and decreased oxidative stress in a vast majority of patients, causing a shift towards an anti-inflammatory pattern particularly at the highest dose tested.
"These results showed a good safety and pharmacokinetic profile of LAU-7b in adult CF patients”, said Dr. Elias Matouk, MD, principal investigator in the study and a clinician-researcher in Respiratory Health at the Research Institute of the MUHC. “We also observed a promising protective effect on certain pharmacodynamic markers, and potential association with stability of clinical parameters, especially during pulmonary exacerbations. LAU-7b is certainly a promising drug candidate for CF and we look forward to its advancement in Phase 2 clinical development.”
The Phase 1b study was a randomized, double-blind, placebo controlled, dose-escalation clinical trial conducted on a single cohort of 15 adult CF patients chronically infected with Pseudomonas aeruginosa. The primary objective was to evaluate the safety, tolerability and the pharmacokinetic profile of a once a day regimen of LAU-7b oral capsules. The secondary objectives of the study included the determination of the doses for the Phase 2 clinical trial, the assessment of pharmacodynamic markers of biologic activity for safety and mechanistic evaluation, and the exploration of pre-specified clinical parameters. Three (3) ascending oral doses of the study drug were administered once a day, in the morning with breakfast, during cycles of 21 consecutive days, followed by a drug-free period.
“We are very pleased with the results of the Phase 1b study and the collaboration with the research team from MUHC. Despite the great advances in the treatment of CF, the aberrant inflammation is still an area of high unmet needs, and is at the core of the inflammation-infection vicious cycle leading to irreversible lung damage”, said Dr. Radu Pislariu, MD, the President and CEO of Laurent Pharmaceuticals. “The few current anti-inflammatory drugs showed limited benefits in CF, thus disease-modifying concepts, such as lipid modulation, could have a better chance to address the still enigmatic link between genetic defect and the compromised host response.”
The Phase 1b study was undertaken following promising preclinical evaluation conducted by RI-MUHC researchers. Oral administration of fenretinide corrected the imbalance between key fatty acids in lungs and plasma of a specific animal model of CF, resulting in reduced lung inflammation and significant decrease in the severity of pulmonary infections with Pseudomonas aeruginosa, a bacterium involved in perpetuating the inflammation-infection vicious cycle in CF.
About Cystic Fibrosis
Cystic Fibrosis is the most common fatal hereditary disease among Caucasians, affecting an estimated 70,000 people worldwide. CF is caused by mutations in the CFTR gene and is characterized by viscous secretions in different exocrine tissues and an aberrant inflammatory response manifested by excessive but inefficient inflammation, leading to pulmonary chronic infection and loss in lung function over time. Severe pulmonary dysfunction is the usual cause of death in CF. 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 plays a major role in the infection-inflammation vicious cycle that leads to respiratory failure.
About Laurent Pharmaceuticals
Laurent Pharmaceuticals is a Montréal-based private biopharmaceutical company. Laurent has a clinical stage lipid modulator (LAU-7b) addressing the compromised immune-inflammatory response in Cystic Fibrosis (CF). LAU-7b is a novel oral solid dosage form of fenretinide, an investigational synthetic retinoid. Preclinical research showed that oral administration of fenretinide corrects the lipid abnormalities in lungs and plasma of specific animal models of CF, resulting in reduced lung inflammation and a dramatic decrease in the severity of pulmonary infections with Pseudomonas aeruginosa, a bacterium involved in perpetuating the inflammation-infection vicious cycle in the lungs of CF patients.
SOURCE: Laurent Pharmaceuticals, Inc.
RELATED LINKS: www.laurentpharma.com