Edesa finds a signal in severely ill Covid-19 patients

But other small biotechs are more advanced and still hope to play a role in the pandemic.

The doubling in value of tiny Edesa Biotech yesterday on mid-stage Covid-19 data in a handful of patients shows that there is still interest in new therapies for the coronavirus, particularly in the inpatient setting. 

Edesa is already making its plans for further trials and expedited review of its anti-toll-like receptor 4 MAb EB05. Other small biotechs are already testing assets with a range of mechanisms in phase 3 or large-scale phase 2 studies. Here, Evaluate Vantage looks at some upcoming readouts. 

TLR4 signalling mediates the lung inflammation that has been shown to be activated by the coronavirus, Edesa says. The phase 2 part of the phase 2/3 trial of EB05 enrolled nearly 400 adults hospitalised with severe Covid-19. They received a single infusion of the antibody, on top of standard of care. More than 90% of recruits received dexamethasone or other steroids as background, and more than 45% received Actemra as well.

28 days later

The trial was unblinded early because its independent data and safety monitoring board saw a marked mortality benefit in a subset of severely ill patients receiving extracorporeal membrane oxygenation (Ecmo) therapy. Another subgroup was seen with "robust signals for mortality reduction at 28 days", according to the press release, although further data has yet to be released. 

Interim data from Edesa's phase 2/3 trial 
  EB05 Placebo
28-day death rate* 14.3% (2/14) 36.8% (7/19)
Reduction in risk of death vs placebo 68.5%  
Stats HR=3.17; p=0.15
*In critically severe patients on ECMO therapy. Source: company release. 

According to Edesa, the monitoring board said this was a “clinically important efficacy signal”, and stated that the study had met its objective. Despite the clear survival delta in favour of EB05 in this group, it is known known whether the trial was a success on any intent to treat analysis. As such, this finding seems likely to be only exploratory. 

The signal also needs to be confirmed in a larger trial. Edesa says it is moving to update the protocols covering the phase 3 portion of the trial to focus on critically severe patients, as well as other populations that might show the strongest efficacy signals. It also hopes to apply for expedited regulatory review in the US and Canada.

Up and coming

Several other independent biotechs are aiming for the same prize, and some will have phase 3 data before Edesa. 

One of the next important readouts in hospitalised patients will come from the phase 3 Sprinter trial of Synairgen’s SNG001. The inhaled project will be given once a day for two weeks, with the aim of showing a benefit over placebo on time to discharge from hospital and time to recovery. Data could come by the end of the year, and if they are positive the interferon beta formulation might very well beat Edesa’s candidate to market. 

Before Sprinter reports, however, Sorrento’s Brazilian phase 2 study of its oral kinase inhibitor AC0010, or abivertinib, will yield data: the company has said this will come by the end of September. The trial’s endpoint concerns the proportion of patients alive and discharged from hospital by day 29. AC0010 is one of no fewer than eight Covid-19 therapies on which Sorrento is working. 

Two more phase 2s, from the private groups Implicit Bioscience and Atriva Therapeutics, could yield data by the end of the year, though the start of 2022 is probably more realistic. And results from Veru’s phase 3 trial of sabizabulin could come in roughly the same time frame. 

Another oral project, sabizabulin is a tubulin inhibitor, believed to have antiviral activity by disrupting the intracellular transport of the virus particles along microtubules. Veru also says it has anti-inflammatory effects that could combat the cytokine storm seen in severe Covid-19 patients. The trial’s primary endpoint is mortality after two months’ treatment. 

Despite a huge clinical effort to find treatments for Covid-19 few have won approval, and notably none used widely in severely ill patients are novel agents. That could still change, of course, and Edesa's share price jump shows that some investors are still playing the opportunity. 

Selected trials of Covid-19 therapies for hospitalised patients
Company Project Mechanism RoA Trial details
Edesa Biotech  EB05 Anti-toll-like receptor 4 MAb IV Ph2, 360 pts, PCD Apr 21
Sorrento Therapeutics AC0010 BTK and EGFR inhibitor Oral Ph2, 400 pts, PCD May 21
Synairgen SNG001 Interferon beta 1a regulator Inhaled Sprinter, Ph3, 610 pts, PCD Oct 21
Implicit Bioscience IC14 Myeloid cell surface antigen CD14 MAb IV Ph2, 300 pts, PCD Nov 21
Atriva Therapeutics ATR-002 MAPK inhibitor Oral Ph2, 220 pts, PCD Dec 21
Veru Sabizabulin/
Tubulin polymerisation inhibitor Oral Ph3, 300pts, PCD Jan 2022
PCD=primary completion date. All trials are recruiting. Source: Evaluate Pharma, clinicaltrials.gov. 

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