Therapeutics to treat COVID-19 could be a key element to plans to reopen the US economy; hundreds of trials are underway. Candidates in development could provide clinical symptom relief, shorten hospital stays or reduce the risk of death. But as the crisis abates in certain parts of the world, it also reveals the challenge in pulling this off—getting the trials fully enrolled.
The flurry of clinical trials for therapeutics to treat COVID-19 is unmatched by previous epidemics in the past decade. Still, it remains unclear, as always, how many, if any, drug candidates will prove safe and effective.
ClinicalTrials.gov lists over 350 clinical studies related to COVID-19, and the World Health Organization (WHO) has a link to over 400 studies in various countries. The FDA has granted a narrow EUA for chloroquine/hydroxychloroquine, and on March 31, the agency launched the Coronavirus Treatment Acceleration Program. The program is intended to provide feedback to companies designing studies to treat COVID-19, review new trial protocols and analyze any new data on potential therapeutics in a rapid fashion.
According to BioCentury, as of April 1, at least 72 therapeutic candidates were in clinical or preclinical testing to treat COVID-19. Among these, 30 are drugs already approved in the US for another indication; nine are approved outside the US.
Anti-infectives make up the largest proportion (30%) of already approved drugs that might be repurposed for COVID-19, followed by cancer treatments (19%) and autoimmune drugs (19%).
Among the 33 agents being studied via an EUA, expanded access or in Phase IV or Phase III testing, an analysis by HRI of the primary endpoint being measured in the trial shows that 32% of the trials are looking at whether the agent has an effect on clinical symptoms such as fever or oxygenation improvement, while 24% are using an event-driven primary endpoint such as changes in mortality, reductions in the time spent in the hospital or patients breathing without a ventilator.
Change or elimination of SARS-CoV-2 viral RNA is the primary endpoint for 16% of these late-stage trials, though they frequently assess the clinical endpoints or outcomes as secondary endpoints. For agents with multiple trials included in ClinicalTrials.gov, HRI limited its analyses to those with trials that were enrolling or active.
The number of drug candidates being tested to treat COVID-19 is much higher than those evaluated during the Ebola crisis in 2014. As of June 2015, about 30 drug candidates were under development to treat Ebola, with five in the clinic. No drugs have yet to be approved to treat Ebola, and one of the challenges, according to the FDA, was that the virus abated, making it difficult to fully enroll trials to understand the efficacy of a given agent.
An HRI analysis of the COVID-19 trials listed by WHO shows that the largest percentage of trials to evaluate a treatment for the virus are in China (70%), which has largely started to reopen its economy after a shutdown to contain the virus in January. The total number of patients required to enroll in all of the trials in China is 36,362. As of April 7, there were fewer than 5,000 active cases of COVID-19 in China.
The US, which, as of April 9, has the largest number of active cases at about 366,000, is home to 15 clinical trials, according to WHO, including three multi-country studies. The total enrollment number for these trials is 12,583. Among the 366 trials listed on ClinicalTrials.gov, only 16 are fully enrolled and not recruiting any more patients; 10 are completed; seven have been withdrawn; and 170 are not yet recruiting patients.
With the US government’s plan of physical distancing to slow the spread extended until April 30, a few emerging plans provide advice on a stepwise approach to reopening the economy and easing the social distancing requirements. Therapeutics are key to some of the most prominent plans.
American Enterprise Institute (AEI) resident fellow Dr. Scott Gottlieb, former commissioner of the FDA, published a plan on March 29 that included multiple considerations and milestones for the transition, including the availability of therapeutic and preventive treatments for patients who could continue to get sick as restrictions are lifted.
To begin to relax physical distancing measures, Gottlieb recommended the acceleration of the R&D, production and distribution of therapeutics that could receive Emergency Use Authorization (EUA). These could serve as prophylaxes to help prevent infection in patients at greatest risk or those at risk of bad outcomes and could come in the form of antibodies that target virus surface antigens or antivirals that target how the drug replicates, Gottlieb wrote.