Candidates: EB05 and EB06
Types: Monoclonal antibodies designed to inhibit the signaling proteins toll-like receptor 4 (TLR4) and CXCL10, respectively. Edesa has said EB05 is designed to suppress inflammation, fluid accumulation and lung injury, thereby reducing the number of patients admitted to intensive care units and intubation/ventilation procedures, thus saving lives.
2021 Status: Mortality Reductions Reported—Edesa said October 19 that EB05 demonstrated mortality reductions in multiple patient groups beyond the findings reported September 20 from the Phase II portion of an ongoing Phase II/III trial (NCT04401475).
The company reported that 136 hospitalized COVID-19 patients receiving supplemental oxygen showed a 28-day mortality rate of 8.2% (5/61) in the EB05 + standard of care (SOC) arm versus 12% (9/75) in the placebo + SOC arm. Within that group, a strong signal for patients with severe ARDS at baseline (based on the Berlin score) was studied by the trial’s Data and Safety Monitoring Board (DSMB) and was part of their decision to unblind the study.
Consistent with a signal previously reported in critically ill patients, the DSMB concluded that the severe ARDS patients receiving supplemental oxygen at baseline had “a clinically important efficacy signal” with a 28-day mortality rate of 16.7% (2/12) in the EB05 + SOC arm versus 42.9% (6/14) in the placebo + SOC arm. Survival Analysis using Cox’s Proportional Hazard Model in this group showed that the subjects treated with EB05 + SOC had a 66% reduction in the risk of dying when compared to placebo + SOC at 28 days.
Edesa also reported confirmatory efficacy signals were detected in other groups including 190 patients with mild to moderate ARDS at baseline, who showed a 28-day mortality rate of 7.8% (7/90) in the EB05 + SOC arm versus 11% (11/100) in the placebo + SOC arm. Within the group, patients with mild to moderate ARDS receiving oxygen support beyond supplemental oxygen showed a 50.7% reduction in the risk of dying in the EB05 + SOC arm compared to placebo + SOC at 28 days. The 28-day mortality rate was 10.8% (4/37) in the EB05 + SOC arm versus 20.5% (8/39) in the placebo + SOC arm. Patients treated with EB05 + SOC also had an increase of approximately 6.1 days alive and free of invasive mechanical ventilation (IMV) at 28 days versus those treated with placebo + SOC.
Edesa President Michael Brooks, PhD, said the company will focus its upcoming Phase III trial on critically ill patients, saying that approach could substantially reduce the number of additional patients needed for the study and “put the company in the position to potentially file for its first marketing authorization application sooner than anticipated.”
Positive Phase II Data—Edesa Biotech said September 20 that critically ill hospitalized patients treated with a single dose of EB05 plus standard of care showed a 68.5% reduction in the risk of dying compared to patients receiving placebo plus standard of care at 28 days, according to an initial analysis of the Phase II portion of an ongoing Phase II/III trial (NCT04401475) by the study’s Data and Safety Monitoring Board (DSMB). The efficacy signal was deemed strong enough that the DSMB requested the study be pre-emptively unblinded.
While the Phase II portion was primarily designed to refine patient stratification and statistical powering for the Phase III study, Edesa said, the DSMB concluded that the study met its objective since “a clinically important efficacy signal” was detected. The DSMB further recommended continuation of the study into its Phase III confirmatory portion.
The analysis reviewed data from approximately 360 patients, ages 24 to 93, from sites in the U.S., Canada, and Colombia. Edesa said it intends to file amendments with regulators in all three countries to update the Phase III protocol and set targeted enrollment.
More Than Double–Investors reacted to Edesa’s positive Phase II news on September 20 with a buying surge that sent the company’s stock price zooming 103%, to $11.92 at the close of trading, from $5.88 on September 17.
Enrollment to Continue–Edesa said June 18 that an independent Data and Safety Monitoring Board (DSMB) had completed an interim review of EB05 and recommended that the company’s international Phase II/III trial (NCT04401475) continue as planned. The DSMB conducted a pre-planned interim review of the first patient cohort participating in the trial, which is evaluating EB05 as a single-dose treatment for hospitalized COVID-19 patients. The DSMB assessed treatment data for safety and futility. After completing its analysis, the DSMB recommended that enrollment in the trial continue.
As of June 16, more than 370 subjects in the U.S., Canada and Colombia had been enrolled in the Phase II/III study. Edesa said it planned to perform the next interim analysis on 316 evaluable subjects once treatment is completed and subject data is validated and aggregated.
On March 15, Edesa said it completed enrollment of more than 50% of the patients planned for the Phase II portion of its ongoing Phase II/ III trial evaluating EB05 as a single-dose treatment for hospitalized COVID-19 patients with or at risk of developing Acute Respiratory Distress Syndrome (ARDS).
More than 160 of the expected 316 subjects in the study’s Phase II portion have been randomized and dosed with either EB05 or placebo at hospital sites across Canada, the U.S., and Colombia. Should EB05 show promising Phase II results, the company plans to continue with a pivotal Phase III study. To prepare for the Phase III portion, Edesa said, it plans to activate approximately 20 additional hospital sites in the next two months.
The Phase II/III trial is an adaptive, double-blind study designed to evaluate the efficacy and safety of EB05 in adult hospitalized COVID-19 patients.
2020 Status: Edesa said October 19 it received FDA clearance to begin the Phase II portion of its Phase II/III trial of EB05 in hospitalized COVID-19 patients. The adaptive, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of EB05 in adult hospitalized patients who have or are at risk of developing acute respiratory distress syndrome (ARDS). Patients will be infused intravenously with a single dose of EB05 or placebo. Should EB05 show promising Phase II results, Edesa said, it plans to continue with a pivotal Phase III trial.
The company has begun site initiation at U.S. hospitals for the trial, whose protocol has previously been approved by Health Canada.
In April, Edesa licensed EB05 and EB06 from Light Chain Bioscience (a brand of NovImmune), with plans to develop the signaling molecules as potential treatments for ARDS and lung injury resulting from viral respiratory infections, such as SARS=CoV-2, and other disorders. Edesa CEO Par Nijhawan, MD, noted that TLR4 and CXCL10 antagonists had been shown to rescue mice from lethal influenza infection and ameliorate virus-induced acute lung injury.
Edesa agreed to issue its Series A-1 Convertible Preferred Shares to Light Chain at an agreed value of $2.5 million with a fixed conversion price, and pay Light Chain up to $6 million near-term for drug product inventory and other milestone fees, plus up to $363.5 million in payments tied to achieving aggregate development, approval and commercial sales milestones. Light Chain is also eligible to receive royalties based on sales. Edesa agreed to oversee development, product registration, and commercialization, and has the option to purchase the candidates during the term of the agreement.
COVID-19: 300 Candidates and Counting
To navigate through the >300 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types:
● ANTIVIRAL
● VAX
● ANTIBODY
● RNA
