Laurent Pharmaceuticals Inc., a clinical-stage biopharmaceutical company developing LAU-7b, a first-in-class pro-resolving drug candidate, reported today topline results from its Phase 2 RESOLUTION clinical trial in hospitalized COVID-19 patients. This double-blind, placebo-controlled trial evaluated the efficacy and safety of once-a-day oral LAU-7b, administered for 14 days on top of standard of care. The trial randomized a total of 232 hospitalized patients with moderate, severe or critical COVID-19 disease, of which 148 patients had moderate-to-severe disease (not requiring oxygen or requiring low-flow oxygenation) and 84 were critically ill COVID-19 patients requiring high-flow oxygen but not mechanical ventilation.
In the overall moderate-to-critical patient population, the study did not meet its primary endpoint of improving the proportion of patients alive and free of respiratory failure on Day 29 (LAU-7b: 81/117 patients, 69.2% versus Placebo: 83/115 patients, 72.2%; p=0.74).
A clinically meaningful efficacy signal was achieved in the pre-specified subgroup moderate-to-severe COVID-19 patients (n=148, representing 64% of the overall study population), with LAU-7b plus standard of care demonstrating a 100% reduction in the risk of all-causes death and the risk of progressing to mechanical ventilation by Day 60, when compared to placebo plus standard of care. More specifically, none of the 76 moderately to severely ill patients treated with LAU-7b plus standard of care died or progressed to mechanical ventilation, while 4 patients died (4/72, 5.6%, p=0.053) and 5 progressed to mechanical ventilation (5/72, 6.9%, p=0.025) in the placebo arm. The study also showed an improvement of 6.9% relative to placebo (p=0.055) in the proportion of patients alive and free of respiratory failure at Day 29 treated with LAU-7b, in this moderate-to-severe COVID-19 patient population.
The results from the moderate-to-severe subgroup are very promising, suggestive of a potential clinical benefit of LAU-7b in COVID-19 patients that are not yet in respiratory failure, which also represents the patient population with the fewest treatment options”, said Radu Pislariu, MD, President and CEO of Laurent Pharmaceuticals. "An oral therapeutic that prevents serious COVID-19 illness and death, also allowing patients to continue the treatment at home after discharge from hospital, would be a powerful tool in the therapeutic arsenal against COVID-19”, added Dr Pislariu.
“Avoiding ventilatory support in this common subset of hospitalized patients is a very desirable goal as it prevents ICU overload and protects the patients from complications that may occur after ventilatory support is initiated”, said Dr Barry Meisenberg, MD, clinical investigator in the RESOLUTION trial. “Subsequent clinical development in a larger moderate-to-severe patient population will allow confirming the positive results observed with LAU-7b” added Dr Meisenberg, who is also the chair of the Department of Medicine of the Anne Arundel Medical Center in Annapolis MD, United States.
LAU-7b was well-tolerated, with a safety profile comparable to the placebo arm and consistent with the existing safety data. The concomitant standard of care was evenly distributed among the treatment arms. The subgroup analysis of critically ill COVID-19 patients didn’t show an improvement in the LAU-7b arm over placebo, suggesting that patients already in respiratory failure at baseline may be too severely affected by the disease to benefit from the LAU-7b treatment.
Based on these results, the company plans to focus its future development on patients with moderate-to-severe COVID-19 disease and on the key endpoints associated with the observed clinical benefit, and will seek guidance from the regulatory agencies on potential strategies moving forward, which may include amending and extending the RESOLUTION trial.
LAU-7b is a novel oral form of fenretinide, an atypical retinoid that acts on certain cell membrane lipids involved in both viral replication and immune-inflammatory responses. LAU-7b was initially developed for its potential to trigger the resolution phase of inflammation, a natural mechanism that keeps the inflammatory response under control, without inducing immune-suppression (a “pro-resolving” effect). More recently, fenretinide was shown to have antiviral activity in vitro against SARS-CoV-2 and synergistic potential when combined with remdesivir, evocative of different mechanism than typical antivirals. LAU-7b is believed to work by decreasing cell membrane fluidity required for virus entry and release, as well as reducing de novo lipid synthesis required for pathogen proliferation.
About Laurent Pharmaceuticals
Laurent Pharmaceuticals is a clinical stage biotech company focusing on the modulation of cell membrane lipids for addressing complex conditions caused by an unbalanced immune-inflammatory response. The company’s lead drug candidate, LAU-7b, is a proprietary oral formulation based on 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 inflammatory-controlling, antifibrotic and antiviral properties. LAU-7b is currently being evaluated as a potential therapeutic for Cystic Fibrosis and COVID-19. For more information, please visit www.laurentpharma.com.