The FDA is amping up work to accelerate COVID-19 therapeutics as multiple studies are expected to kick off in the coming weeks. As data trickle in on some of the first agents designed to specifically target the SARS-CoV-2 virus, infections are decreasing in some parts of the US while rising in others. This ebb and flow of the virus across the US likely will be a factor in the success of clinical trials of therapeutics aimed at SARS-CoV-2 and COVID-19.
According to BioCentury, the collaborative Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) is expected to start its first trials in June, with others following in July for both hospitalized and outpatient individuals diagnosed with COVID-19.
The public-private partnership includes the FDA, the National Institutes of Health, the Biomedical Advanced Research and Development Authority, the Centers for Disease Control and Prevention, the Defense and Veterans Affairs departments, and the European Medicines Agency (EMA), along with biopharma companies. The program is working with the White House’s Operation Warp Speed, which was launched last month to accelerate the development of therapeutics and vaccines for COVID-19.
ACTIV will use master protocols to test agents directed at different elements of the infection, including a study of immune modulating agents as well as a separate study assessing the benefits of anticoagulants in hospitalized patients with severe cases involving coagulation abnormalities.
Other studies coordinated by ACTIV will test antibodies that directly target the virus. Master protocols are considered to be an efficient means to conduct studies of multiple agents for a single condition and have been endorsed by the FDA and the World Health Organization to test therapeutics and vaccines for COVD-19.
The overwhelming majority of agents in the clinic to treat patients infected with SARS-CoV-2, which causes COVID-19, are repurposed drugs that were developed for another disease but which may, based on their mechanism of action, benefit patients infected with the virus (or prevent infection in the first place).
HRI’s analysis of the 170 therapeutics in the clinic as of June 15 found that 82 are approved for another indication in the US or elsewhere. Twenty percent of these agents are approved for infectious diseases; 16% for cancer; 13% for autoimmune indications; and 13% for cardiometabolic conditions. The analysis excludes agents offered under expanded access or planned trials.
However, in the past few weeks, antibodies developed to target specific proteins on the SARS-CoV-2 virus have entered the clinic (see here, here and here). Early safety data for some of these programs could start to emerge later this month.
The acceleration in new therapeutics for COVID-19 comes as the FDA has revoked the first Emergency Use Authorizations (EUAs) it granted for therapeutics—chloroquine and hydroxychloroquine—leaving one other agent and one device available for treatment under separate EUAs for COVID-19.
Nonetheless, FDA Commissioner Stephen Hahn said on June 1 that more than 144 clinical trials had been started for COVID-19 therapies in the US and that the agency was working with drug developers to “explore, expedite and incentivize the development of these products.”
The rush to develop therapeutics to treat COVID-19 has outmatched previous efforts for infectious disease outbreaks. But as other countries tamp down the infection and many states continue to see cases level off, researchers could wind up being able to test fewer agents to completion.
The number of therapeutics in the clinic now for COVID-19 has more than doubled since April, when there were 72, and far outpaces the 30 drug candidates that were under development to treat Ebola during the 2014 crisis.
However, none of the Ebola therapeutics were developed to completion because the virus subsided.
As of June 16, among the 1,233 interventional trials for COVID-19 listed on ClinicalTrials.gov, 488 were not yet recruiting while 29 were suspended, withdrawn or terminated, eight of which listed an inability to recruit patients as the reason.
According to the Johns Hopkins University of Medicine COVID-19 dashboard as of June 17, some of the harder-hit regions of the US, such as Illinois, New Jersey and New York, continue to see a drop in the number of daily cases just as parts of the southern US are starting to see an increase, including Arizona and Texas. However, only 15 of the COVID-19 trials recruiting or not yet recruiting patients on ClinicalTrials.gov were in Arizona; 34 had sites in Texas.
An April policy from CMS incentivizes some providers to enroll COVID-19 patients into trials, but new data showing the first evidence of a drug to reduce mortality for COVID-19 patients on ventilators could make physicians hesitant to enroll patients in a trial where the outcome is uncertain.