MONTREAL--(BUSINESS WIRE)--Laurent Pharmaceuticals Inc. (the “Company”), a clinical-stage biopharmaceutical company developing LAU-7b (oral fenretinide) as a first-in-class inflammation-controlling drug candidate for Cystic Fibrosis (CF), announces the presentation of results from its placebo-controlled Phase 2 APPLAUD 24-week clinical study in adults with CF at the North American Cystic Fibrosis Conference (NACFC) currently held in Philadelphia, United States.
Study results achieved a statistically significant treatment difference in favour of LAU-7b in the absolute change in the percent predicted forced expiratory volume in one second (ppFEV1), the primary variable, through 24 weeks (1.23 percentage points; p=0.0486) in people that completed at least five months of treatment (Per Protocol population, N=122), and a clinically meaningful reduction of 49% in the loss of lung function at 24 weeks, relative to placebo. Statistically significant clinical benefit was also observed in the relative change in ppFEV1 through 24 weeks (2.34 percentage points; p=0.0351), as well as in the plasma levels of C-reactive protein (p=0.029), an important marker of systemic inflammation. Pre-specified subgroup analysis suggests a higher benefit in subjects with ppFEV1 greater than 70% at baseline, and the effect appears to be maintained in the subgroup of subjects already receiving CFTR modulators, including TRIKAFTA®. The results also passed robustness analyses, despite heterogeneous study population and pandemic interference. The study confirmed that LAU-7b has a predictable and acceptable safety profile, with no unexpected serious adverse events reported.
“The potential clinical benefits of reducing the loss of lung function demonstrated with LAU-7b in the APPLAUD study, especially when administrated on top of CFTR modulators, are very promising and represent a first with a drug candidate addressing inflammation in adults with CF,” said Michael Konstan, MD, Vice Dean for Translational Research at Case Western Reserve University School of Medicine in Cleveland, and Co-Lead Investigator for the study.
“It is really exciting to see this significant progress toward bringing medicines targeting loss of lung function in people with CF, an important and rather neglected aspect of this disease,” added Larry Lands, MD, PhD, Director, Pediatric Respiratory Medicine at McGill University Health Centre in Montreal, and Co-Lead Investigator for the study. “These results showed that the proposed LAU-7b treatment approach is complementary to CFTR modulation, confirming earlier preclinical research by McGill researchers demonstrating LAU-7b’s potential to rescue and preserve CFTR modulator’s effect during cellular stress.”
“These results underscore the important clinical benefit potential of LAU-7b and Laurent’s commitment to delivering the next scientific breakthrough in this disease,” said Radu Pislariu, MD, President and CEO of Laurent Pharmaceuticals. “We want to thank all study participants and their families who put their trust in us, the staff at the clinical sites, the Cystic Fibrosis Foundation, and all our collaborators for their support and partnership throughout this study, conducted in unprecedented pandemic conditions.”
The key outcomes from the study are presented in NACFC Poster #168, and were selected for oral presentation as part of the Session W21 (Evidence Based Medicine - Update on Clinical Trials in CF).
About the Phase 2 APPLAUD clinical study
APPLAUD was a double-blind, placebo-controlled study in adults with CF, randomized (1:1) to LAU-7b or placebo for 6 months. The goal of the study was to evaluate the safety of LAU-7b and its effect on preservation of lung function by reducing inflammation. Eligible subjects had ppFEV1 between 40% and 100% at screening and had had at least one pulmonary exacerbation (PEx) in the prior year. The study drug was administered orally once daily, in addition to standard of care, including all commercially available CFTR modulators. The primary efficacy endpoint was the absolute change from baseline in ppFEV1 at 24 weeks. Secondary endpoints included parameters related to PEx, systemic inflammatory and lipidomic biomarkers, and quality of life. Study randomized 166 adults with CF at 40 sites in the US, Canada and Australia, of which 122 completed a minimum five months of study medication (Per Protocol population). Both arms were very comparable in terms of age, BMI, gender distribution and lung function at baseline. The safety and efficacy profile in this study supports the use of ppFEV1 as the primary efficacy variable for confirmatory studies, with longer treatment duration.
About Cystic Fibrosis
Cystic Fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people worldwide. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene and is characterized by viscous secretions in different exocrine tissues, and an aberrant inflammatory response leading to chronic pulmonary infection and loss in lung function over time. Severe pulmonary dysfunction is the primary cause of death in CF.
About LAU-7b
LAU-7b (oral fenretinide) is a novel drug candidate that acts on cell membrane lipids to modulate inflammation signaling and protein trafficking. Membrane lipid imbalance is believed to play a role in aberrant pulmonary inflammation in individuals with CF, leading to irreversible lung damage over time. Fenretinide was shown to correct the levels of certain membrane phospholipids and sphingolipids in multiple in vitro and in vivo models of CF, improving resolution of inflammation and the stabilization of CFTR in the epithelial apical membrane during inflammatory stress, a self-protective mechanism complementary to CFTR modulators.
About Laurent Pharmaceuticals
Laurent Pharmaceuticals is a clinical stage biotech company focusing on the modulation of cell membrane lipids for addressing life-threatening diseases. The company’s lead drug candidate, LAU-7b, is a proprietary oral formulation of fenretinide, an atypical retinoid with a well-documented safety profile established in more than 3,000 patients. Existing data suggest that low-dose fenretinide has the potential to modulate certain membrane lipids and exerts antiviral, inflammatory-controlling, and antifibrotic properties. LAU-7b is currently being evaluated as a potential therapeutic for COVID-19 and Cystic Fibrosis. For more information, please visit www.laurentpharma.com.
