More than 70 clinical trials have registered with the Food and Drug Administration.
With coronavirus infections and deaths mounting in the United States, the race to find treatments and vaccines is accelerating. There are now 72 registered clinical trials ongoing in the U.S. and abroad, according to the Food and Drug Administration. Here’s a rundown of how this process is taking shape, and the key results expected in the coming months.
Gilead’s experimental antiviral drug was developed to treat Ebola but failed for that purpose. Now, remdesivir has been repositioned as a potential coronavirus therapy. The hype around the drug has grown after the New England Journal of Medicine published promising but anecdotal results from compassionate use and STAT News reported on leaked data from a clinical trial in Chicago. The first official results from clinical trials are expected by the end of the month.
Gilead is running two Phase III trials in the U.S., Asia and Europe. One aims to enroll 6,000 severely ill patients, while the second is seeking 600 moderately ill participants. Both are “open label,” meaning that both doctor and patient know which treatment the patient is receiving. The severe trial is expected to report results in late April, with data from the moderate trial coming in late May.
The National Institute of Allergy and Infectious Diseases — the agency run by Anthony Fauci — has launched the first randomized, controlled trial of remdesivir, enlisting about 1,060 patients worldwide. Results are expected in late May.
Two Chinese trials were halted this month because of a lack of enrollment, purportedly due to a lack of patients with Covid-19 as China’s outbreak wanes.
Outside of the trials, Gilead is still allowing patients to access the intravenous drug via a compassionate use program. It’s donating 1.5 million doses — enough to treat more than 140,000 patients — for use in clinical trials and compassionate use programs.
Approved in Japan in 2014 to treat the flu, Fujifilm’s antiviral — brand name Avigan — never hit the market because of concerns it could cause birth defects. It’s now being tested against the coronavirus in Japan and the U.S. The Japanese government is also stockpiling 2 million treatment courses of the drug, betting that it will be effective because it disrupts the process by which the coronavirus, and related viruses, replicate.
Fujifilm launched a Phase III clinical trial in Japan on March 31 to assess favipiravir’s safety and efficacy. The company did not provide any further details on the trial’s design or duration.
The company also started a Phase II trial this month for about 50 patients at three Boston-area hospitals, including Brigham and Women’s Hospital, Massachusetts General Hospital and the University of Massachusetts Memorial Medical Center.
Zhang Xinmin, an official at China’s science and technology ministry, told the China Daily last month that favipiravir produced encouraging results in clinical trials of 340 patients in Wuhan and Shenzhen.
First approved by the FDA in 2010 to treat rheumatoid arthritis, Roche’s drug — marketed as Actemra — blocks a type of severe inflammation, called a “cytokine storm,” seen in the lungs of some coronavirus patients. Studies from China have shown that neutralizing cytokine storms helps to reduce deaths in severe cases of Covid-19. Last month, China approved the use of Actemra to treat Covid-19, but clinical trials of the drug are continuing.
Results from an open-label trial in France showed improved outcomes for people taking the drug who had moderate or severe Covid-19 pneumonia. The trial compared 65 participants randomly assigned to receive tocilizumab and 64 who were given standard care.
Roche is sponsoring a Phase III trial of 330 hospitalized patients with severe Covid-19 pneumonia in the U.S. and Europe. It will evaluate the efficacy and safety of tocilizumab compared with a placebo in combination with standard treatment. A Roche spokesperson said the results could be released in early summer.
The National Cancer Institute of Naples has enrolled 2,111 people across Italy in a Phase II “single-arm” trial — which means that every patient will receive tocilizumab, and there is no control group. The researcher leading the trial told POLITICO that results are expected in the next three weeks.
At least four other trials are ongoing at hospitals across China, Roche said, but they are not placebo-controlled.
Approved by the FDA to treat rheumatoid arthritis, this Eli Lilly drug — a.k.a. Olumiant — was identified as a potential coronavirus treatment by a U.K.-based artificial intelligence system. Lilly initially expressed caution about using baricitinib in Covid-19 patients because it suppresses the immune system, according to The New York Times, but eventually agreed to test the medication because doctors had started using it off-label. The drug company is working with the National Institute of Allergy and Infectious Diseases to study baricitinib as part of a placebo-controlled trial in the U.S., Europe and Asia that also includes Gilead’s remdesivir. Data on baricitinib is expected in the next two months, according to Lilly.
AstraZeneca’s drug, also known as Calquence, is approved to creat a pair of blood cancers: chronic lymphocytic leukemia and mantle cell lymphoma. Now it’s being eyed as a treatment for coronavirus patients in the grip of cytokine storms. The drug company said last week that it will undertake a randomized, controlled trial of Calquence. NIH Director Francis Collins said this week that he was surprised by the early clinical data, but he also said he’ll wait for the trial results before drawing any conclusions about the drug’s usefulness.
Convalescent plasma is a decades-old treatment that involves giving sick patients the antibody-rich blood plasma of people who have recovered from the same illness. The approach has a mixed track record, but it’s being tried again with the coronavirus — as is a treatment known as hyperimmune globulin, which is derived from convalescent plasma and also contains high levels of antibodies.
New Jersey-based Hackensack University Medical Center is running a Phase IIa study with 55 participants to determine the best dosing for convalescent plasma treatment.
Erasmus University Medical Center in the Netherlands is recruiting 426 patients for a Phase II trial to compare convalescent plasma with the standard of care.
Nine hospitals in Spain will enroll 278 hospitalized patients with Covid-19 to compare convalescent plasma with the standard of care.
The FDA is also helping to coordinate a study of hyperimmune globulin that will be conducted by the National Institute of Allergy and Infectious Diseases.
Hospitals in China have used corticosteroids in an attempt to tamp down inflammation in coronavirus patients, but it’s not yet clear whether this strategy is effective, according to the Centers for Disease Control and Prevention. The agency has warned against using the drugs to treat Covid-19, because patients with the MERS coronavirus or flu who were given steroids were more likely to die than those didn’t get the drugs. Still, there are multiple trials now testing various steroids against the coronavirus.
A U.K. government-funded study of 5,262 Covid-19 patients at 167 sites that began in March is testing four different treatments, including a low dose of the steroid dexamethasone.
Scientists in South Korea are recruiting 144 people to investigate whether the steroid ciclesonide alone or in combination with hydroxychloroquine could help patients with mild Covid-19.
Hydroxychloroquine and chloroquine
The malaria drugs have been at the center of a media storm, after President Donald Trump and his allies began aggressively promoting them as coronavirus treatments despite a lack of data. Pharmaceutical companies have donated millions of doses to the U.S. Strategic National Stockpile, and almost 100 clinical trials have sprung up since the FDA issued an emergency use authorization in early April to distribute the both drugs to coronavirus patients.
At least one clinical trial of hydroxychloroquine was halted because the drug caused life-threatening cardiac side effects — a risk long known to doctors who use the drug to treat lupus and rheumatoid arthritis.
The NIH’s National Heart, Lung and Blood Institute is helping to conduct a blinded, placebo-controlled Phase III trial to evaluate the safety and effectiveness of hydroxychloroquine in 510 adults hospitalized with Covid-19. The trial began enrolling patients in Tennessee on April 2, and will extend to 44 sites nationwide. A spokesperson for Vanderbilt University Medical Center said results will come in “a couple of months.”
The University of Minnesota is conducting a Phase III trial in 3,000 participants to determine if hydroxychloroquine can help prevent or treat Covid-19. Results are expected about two weeks after the trial is fully enrolled, a university spokesperson said.
Trials at the University of Utah and Intermountain Medical Centerin Utah are comparing hydroxychloroquine and azithromycin in 300 patients hospitalized with Covid-19. The timing of its results depends on how quickly researchers can enroll participants, said Dr. Samuel Brown, Intermountain’s director of pulmonary and critical care research.
Three hospitals in New Jersey are conducting a 160-person randomized trial that will compare hydroxychloroquine alone and in combination with the antibiotic azithromycin to a control group that receives standard care for the first six days. After that point, any patients with symptoms of the coronavirus will receive the malaria drug.
The University of Pennsylvania is conducting a three-part trial that includes a randomized, controlled study of hydroxychloroquine as a treatment for home-bound coronavirus patients; a randomized trial testing different doses of the drug in hospitalized patients; and a randomized, controlled trial of low doses of hydroxychloroquine as a preventative treatment for health care workers.
Moderna’s mRNA vaccine
It took just 63 days from the time the company started designing its vaccine to launch the first clinical trial, a rapid pace made possible in part by Moderna’s use of genetic material called messenger RNA. When that mRNA is injected into a patient, it directs cells to make a protein found on the coronavirus — and stimulates the production of antibodies.
No mRNA vaccine for any disease has yet won approval, but the technique has tantalized public health experts because churning out doses using this technology would be cheaper and easier than making traditional vaccines. The U.S. government’s Biomedical Advanced Research and Development Authority has pledged up to $483 million to accelerate the Moderna vaccine’s path to FDA approval.
In March, the Kaiser Permanente Washington Health Research Institute in Seattle began enrolling patients in a Phase I safety trial. Emory University in Atlanta is also enrolling patients in the trial, which is aiming for a total of 45 participants across the two sites. Participants will receive two shots of the experimental vaccine approximately one month apart and will be followed for about one year.
Moderna is already ramping up production of the vaccine for a potential Phase II trial that could begin as early as June. A Phase III trial could begin next fall. If the early data is promising, the company says it could churn out enough doses by next fall to vaccinate health care workers and other priority groups.
CanSino Biologics and Beijing Institute of Biotechnology vaccine
This experimental vaccine, developed in China, was created to combat Ebola. It uses an inactivated version of a virus that causes the common cold to carry a gene that causes cells to make a protein found on the coronavirus — with the goal of sparking an immune response. Phase I testing began last month in China, and CanSino and the Beijing institute have enrolled almost 300 people with Covid-19. Based on preliminary data, the company says it plans to launch a Phase II placebo-controlled trial with 500 participants.
Johnson & Johnson, Beth Israel Deaconess Medical Center and BARDA vaccine
Johnson & Johnson is working with the Biomedical Advanced Research and Development Authority and Boston-based Beth Israel Deaconess Medical Center on a vaccine that uses an inactivated version of the common-cold virus to carry genetic material into cells. That material prompts the body to pump out proteins found in the coronavirus in the hopes of drawing an immune response. The company expects to kick off human studies by September at the latest. If the vaccine works, J&J says the first batches could be available for emergency use in early 2021.
Pfizer and BioNTech vaccine
The two companies — one American, one German — are partnering on an mRNA coronavirus vaccine. This week, German regulators approved a Phase I/II trial of the vaccine; its first stage will enroll 200 people. Pfizer is paying BioNTech $185 million upfront as part of the collaboration, and the companies said they have the potential to supply millions of doses by the end of 2020 if the vaccine is promising, and scale up to produce hundreds of millions of doses in 2021.
Sanofi and GlaxoSmithKline vaccine
This experimental vaccine combines Sanofi technology that produces a protein found in the coronavirus, which aims to trigger an immune response, with an adjuvant made by GlaxoSmithKline designed to heighten that immune response. The companies plan to begin Phase I trials of their vaccine in the second half of the year, and if the results look good, a vaccine could be available by the second half of 2021. Phase I clinical trials are expected to initiate in the second half of 2020 and, if successful, a vaccine could be available by the second half of 2021.