EDSA: Phase 3 study in ARDS expanded to include mechanically ventilated patients…

By David Bautz, PhD

NASDAQ: EDSA

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Commercial Update

Phase 3 study in ARDS expanded to include patients on mechanical ventilation

In May 2022, Edesa Biotech, Inc. EDSA announced the start of enrollment of a second cohort of patients for the Phase 3 Phase 2/3 trial of EB05 in a critical condition of COVID-19 patients with Acute Respiratory Distress Syndrome (ARDS). The first cohort consists of critically ill COVID-19 patients who receive extracorporeal membrane oxygenation (ECMO) and/or invasive mechanical ventilation plus organ support, defined as Level 7 on the COVID-19 Severity Scale of the World Health Organization. The second cohort will be composed of hospitalized COVID-19 patients on invasive mechanical ventilation alone (WHO level 6).

The primary endpoint for the level 7 cohort will be 28-day mortality. Secondary endpoints will assess ventilator-free days and 60-day mortality. The protocol approved by Health Canada provides for the enrollment of approximately 315 evaluable subjects.

The primary endpoint for the level 6 cohort will be the number of ventilator-free days at day 28. The secondary endpoints will include ventilator-free days at day 60 as well as the 28- and 60-day mortality rates The protocol for the Level 6 cohort calls for the enrollment of approximately 500 evaluable subjects.

The inclusion of Tier 6 and Tier 7 patient populations has already been approved by regulatory bodies in Canada, Colombia and Poland. Edesa initially focused on Level 7 patients, as they are the most severe cohort with the most urgent medical need. Enrollment of the two cohorts being assessed will take place in parallel and each cohort will be assessed independently.

The company has filed a similar protocol with the US FDA and is currently in discussions with the agency on the design of the final Phase 3 protocol.

In September 2021, Edesa announced positive results from the Phase 2 trial which included approximately 360 patients, ages 24 to 93, from clinical trial sites in the States United States, Canada and Colombia. The Independent Data and Safety Monitoring Board (DSMB) identified a large treatment effect on 28-day mortality in which treatment with EB05 in addition to standard of care (SOC) resulted in a reduction of 68, 5% risk of death compared to placebo and requested that the study be unblinded as a preventive measure. The Phase 2 study was originally designed to guide patient stratification and statistical feeding of the Phase 3 trial, but the DSMB noted that "a clinically important signal of efficacy" has been detected as well as the fact that the study "achieved its objective". . In addition, the DSMB has recommended that the study continue in a confirmatory phase 3 trial.

In October 2021, Edesa announced additional Phase 2 results from the ongoing Phase 2/3 clinical trial of EB05:

• The DSMB noted a mortality benefit in 136 hospitalized COVID-19 patients receiving supplemental oxygen (28-day mortality rate of 8.2% [5/ 61] in the EB05 + SOC arm vs. 12.0% [9/75] in the placebo + SOC arm; HR = 1.52). In this group, there was a strong signal for patients with severe acute respiratory distress syndrome (ARDS) at baseline (defined as PaO2/FiO2 < 100 mm Hg). The DSMB concluded that patients with severe ARDS receiving supplemental oxygen at baseline had "a clinically important signal of efficacy" with a 28-day mortality rate of 16.7% (2/12) in the arm EB05 + SOC versus 42.9% (6/14) in the placebo + SOC arm. This corresponds to a 66.0% reduction in the risk of death at day 28 for subjects treated with EB05 + SOC compared to placebo + SOC (HR = 2.94, 95% CI: 0.59 - 14.60 ; P=0.19) when using the Cox proportional hazard model.

• Efficacy signals were also noted in the 190 patients with mild to moderate ARDS at baseline (28-day mortality rate of 7.8% [7/90] in the EB05 + SOC arm vs. 11.0% [11/100] in the placebo + SOC arm; HR = 1.46). Among this group, patients with mild to moderate ARDS receiving oxygen beyond supplemental oxygen had a 28-day mortality rate of 10....