The Status of COVID-19 Therapeutic and Vaccine Trials

For clinicians on the front lines treating patients with COVID-19, it has been a long and winding road to determine therapeutics that are effective in reducing the severity of illness, shortening hospitalizations or through other indicators of effectiveness, reducing the morbidity and mortality of this novel disease. At the time of our “The Search for a Solution” blog on March 24, the U.S. National Library of Medicine was tracking seven active trials being conducted in the U.S., including six therapeutics and one potential vaccine.  A little over seven months later, some 866 studies are underway in this country alone, with another 2,941 trials being conducted worldwide. 

So, what lessons have scientists learned from the over 47 million cases and 1.2 million deaths that have been identified and recorded this year?

Mitigating COVID-19’s Impact with Therapeutics

Three therapeutics have been approved to treat COVID-19: 

•  Dexamethasone in the United Kingdom and Japan 
• Avigan (favilavir) in China, Italy and Russia
• Veklury (remdesivir) in the United States, Japan and Australia

Many other treatments have been tested in hospital settings under emergency use authorization or via investigational new drug applications. For example, convalescent plasma may be used in the U.S. to treat hospitalized patients, however updated guidance from the Food and Drug Administration (FDA) notes that “Adequate and well-controlled randomized trials remain necessary for a definitive demonstration of COVID-19 convalescent plasma efficacy and to determine the optimal product attributes and appropriate patient populations for its use”.

Hydroxychloroquine, an immunosuppressive and anti-malarial drug received considerable media attention and was once considered a leading candidate, however evidence has shown it can cause more harm than benefit in patients with COVID-19.

Collaborative Methods

The pandemic has created unprecedented speed and collaboration among researchers and scientists from the international community. One of the largest international randomized trials for COVID-19 treatments, sponsored by the World Health Organization (WHO) and partners is called Solidarity, enrolling almost 12,000 patients in 500 hospital sites in over 30 countries.

The Solidarity Trial is evaluating the effect of drugs on three important outcomes in COVID-19 patients: mortality, need for assisted ventilation, and duration of hospital stay. The Solidarity Trial published interim results on October 15, 2020. It found that all four treatments evaluated (remdesivir, hydroxychloroquine, lopinavir/ritonavir and interferon) had little or no effect on overall mortality, initiation of ventilation and duration of hospital stay in hospitalized patients. The Solidarity Trial is considering evaluating other treatments, to continue the search for effective COVID-19 therapeutics. Per the WHO Solidarity Trial site, so far, only corticosteroids have been proven effective against severe and critical COVID-19.

Corticosteroids appear to be associated with benefit among critically-ill patients with COVID-19 whether they are receiving mechanical ventilation or oxygen without mechanical ventilation. A meta-analysis conducted to review standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome or Middle East respiratory syndrome indicates that administration of steroids is clearly associated with benefit among critically-ill patients with COVID-19, although the exact threshold at which an individual patient should be prescribed corticosteroids remains unclear.

Many Vaccine Candidates in the Pipeline

With so much research underway on therapeutic approaches, and only a handful of effective treatments being identified, a parallel and concerted effort continues in the development of vaccine candidates for COVID-19. Fifty-one candidate vaccines are undergoing Phase 1-3 clinical trials as well as candidates in pre-clinical stages of development and research according to the Regulatory Affairs Professional Society’s COVID-19 Vaccine tracker. Operation Warp Speed, a collaboration of several U.S. federal government departments and the private sector has selected three vaccine candidates to fund for Phase 3 trials. Other key international research collaborations such as COVAX and the new National Institutes of Health sponsored COVID-19 Prevention Trials Network are working around the clock to enroll thousands of volunteers in large-scale clinical trials testing a variety of investigational vaccines and monoclonal antibodies intended to protect people from COVID-19. 

This Herculean effort suggests that a fast-tracked vaccine could come to the market anywhere from the end of 2020 to the middle of 2021. In this unprecedented year, it is comforting to know hundreds of thousands of scientists, physicians, patients and researchers are working around the clock to pursue both effective therapeutics to mitigate the impact of COVID-19 illness and to develop vaccines that will hopefully provide protection against this deadly pandemic.