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Oral Covid-19 Antiviral Candidate LAU-7b Demonstrates 100[percnt] Reduction of the Risk of Progression to Mechanical Ventilation and Death in Hospitalized Moderate-to-Severe Covid-19 Patients
American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927923
ABSTRACT
Rationale LAU-7b is developed as a broadly effective oral COVID-19 therapeutic targeting membrane lipids to exert dual antiviral and inflammation-controlling activity. SARS-CoV-2 reprograms host cellular lipid metabolism to favor entry and replication, a mechanism shared by all lipid-enveloped viruses. LAU-7b decreases host cell membrane lipids fluidity, inhibits de-novo cell lipogenesis, and modulates phospholipid signaling promoting resolution of inflammation. Due to its host-directed mutation-agnostic mechanism, LAU-7b utility could span across future variants, as demonstrated in-vitro against multiple SARS-CoV-2 strains and MERS-CoV. RESOLUTION, a large Phase 2/3 study evaluating LAU-7b in hospitalized COVID-19 patients, is ongoing in the US and Canada, and preliminary Phase 2 results are presented.

Methods:

RESOLUTION is a placebocontrolled study of oral LAU-7b, once-a-day for 14 days on top of standard of care, in hospitalized COVID-19 patients at risk of developing pulmonary complications. The Phase 2 portion of the study randomized 148 patients with moderate-to-severe COVID-19 and 84 patients in critical condition, but not on invasive ventilation. Key endpoints included proportion of patients alive and free of respiratory failure at Day 29, rates of progression to mechanical ventilation and all-causes death by Day 60, time to recovery and length of hospitalization.

Results:

Both study arms were highly comparable in terms of mean age, number of comorbidities and concomitant medications. LAU-7b demonstrated a 100% reduction in the risk of progressing to mechanical ventilation or death by Day 60 in moderate-to-severe COVID-19 patients. None of the 76 patients on LAU-7b required mechanical ventilation and none died, while 5 out of 72 patients on placebo progressed to mechanical ventilation (6.9% difference, p=0.025), and 4 patients died (5.6% difference, p=0.053). LAU-7b group also showed an increase of 6.9% (p=0.055) in the proportion of patients alive and free of respiratory failure at Day 29, versus placebo. Patients on LAU-7b tended to recover more rapidly and leave hospital faster. LAU-7b was well-tolerated, with safety comparable to placebo. Critically ill patients treated with LAU-7b did not show improvement over placebo, suggesting that COVID-19 patients in respiratory failure at baseline are too severely affected to benefit.

Conclusion:

LAU-7b showed positive results in the trial's Phase 2 portion on both survival and avoidance of mechanical ventilation in moderate-to-severe COVID-19. The confirmatory Phase 3 portion was triggered and received approval from the FDA and Health Canada, focusing on moderate-to-severe COVID-19 and using the “Proportion of patients requiring mechanical ventilation and/or death by Day 60” as primary efficacy endpoint.
Keywords

Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: American Journal of Respiratory and Critical Care Medicine Year: 2022 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: American Journal of Respiratory and Critical Care Medicine Year: 2022 Document Type: Article