Covid-19 research efforts slow
A few developers are still finding reasons to research novel pandemic treatments, though much of the ongoing work is focused on proven approaches.
As the coronavirus pandemic has slowly been brought under control, efforts to find effective treatments have inevitably dimmed. But not by as much as might be assumed.
Pandemic-related clinical activity peaked in April 2020, when more than 300 studies of potential Covid-19 therapies were registered on the registry clinicaltrials.gov. By April this year that had dropped to around 100, and activity has fallen again since. Industry-sponsored studies of unapproved agents represent a small proportion of these numbers, but this analysis finds that a handful of developers are still initiating work with novel projects.
Foresee Pharmaceuticals, for example, earlier this year started a phase 2/3 trial of its MMP-12 inhibitor FP-025 in severely ill patients with acute respiratory distress syndrome. And Pfizer is collaborating with an academic researcher on a trial of its Irak 4 inhibitor PF-06650833, again attempting to help very sick Covid-19 sufferers.
Projects classified as novel in the chart below were unapproved in any indication when the pandemic started, although some have since been authorised for Covid-19. The "All Covid-19 trials" grouping also includes studies of repurposed drugs and those sponsored by academic or government groups.
The vast majority of trials captured in this Evaluate Vantage analysis are of vaccines and monoclonal antibodies, many of which have now made it to market. These newly approved Covid-19 projects are considered novel for the purposes of this analysis.
And, while the bulk of the clinical work was started in 2020, this year has still been pretty active so far. By the end of August 165 trials of unapproved projects were listed on CT.gov. A caveat is that 51 of these have been registered but have not started enrolling – assuming that clinical trial entries are kept up to date – suggesting that the impetus for running these research programmes is waning.
A big proportion – 96 of these 165 – are testing vaccines and monoclonal antibodies. Small molecules are also being vigorously pursued, largely reflecting efforts to find an oral antiviral, and improve on the dubious efficacy of Gilead’s Veklury.
This week’s failure of Redhill's contender opaganib serves as a reminder of how tough oral antiviral development is proving. This setback followed Merck & Co’s decision to scrap work in hospitalised patients with the Ridgeback-partnered molnupiravir. Roche/Atea’s AT-527 and Novartis/Molecular Partners intravenous candidate ensovibep are other closely watched antiviral projects, and count for a good number of the trials in this analysis.
But what of attempts outside these main thrusts of research? The table below highlights a few notable large ongoing trials of unapproved agents. These are few and far between, however, and much of the ongoing research focuses on confirming and refining the efficacy signals seen with proven mechanisms.
Still, breakthrough infections and vaccine hesitancy mean that hospitals have plenty of very sick Covid-19 patients in need of care. Some developers apparently remain convinced that there are roles to find. Unfortunately, the high failure rate seen outside of vaccines and antibodies provides a constant reminder that, at its severest form, this remains a very hard-to-treat viral disease.
|Selected ongoing large trials of novel agents for Covid-19|
|Project||Mechanism||Company||Trial ID (Recruitment)|
|Novaferon||Inhaled interferon||Genova Biotech||NCT04669015 (914)|
|SNG001||Inhaled interferon-β||Synairgen||NCT04732949 (610)|
|FP-025||MMP-12 inhibitor||Foresee Pharmaceuticals||NCT04750278 (403)|
|AC0010||Anti-EGFR/BTK kinase inhibitor||Sorrento Therapeutics||NCT04528667 (400)|
|Upamostat||Serine protease inhibitor||Redhill Biopharma||NCT04723537 (310)|
|Source: Evaluate Pharma & clinicaltrials.gov.|