Here’s Exactly Where We Are with Vaccines & Treatments for COVID-19

Here’s Exactly Where We Are with Vaccines & Treatments for COVID-19

06/05/2020

healthline.com

With confirmed COVID-19 cases worldwide surpassing 6.4 million and continuing to grow, scientists are pushing forward with efforts to develop vaccines and treatments to slow the pandemic and lessen the disease’s damage.

Some of the earliest treatments will likely be drugs that are already approved for other conditions or have been tested on other viruses.

“People are looking into whether existing antivirals might work or whether new drugs could be developed to try to tackle the virus,” said Dr. Bruce Y. Lee, a professor at the CUNY Graduate School of Public Health & Health Policy.

As of May 8, three medications had received emergency use authorization (EUA) from the Food and Drug Administration (FDA) — the anti-malaria drugs chloroquine and hydroxychloroquine, the anti-viral remdesivir, and a drug used to sedate people on a ventilator.
A EUA allows doctors to use these drugs to treat people with COVID-19 even before the medications have gone through the formal FDA approval process. In mid-May, the small biotech company, Sorrento Therapeutics, announced it has an antibody-drug that has been effective in early testing in blocking the virus that causes COVID-19. They say the drug could potentially be used to treat people with COVID-19 as well as help prevent infection.
These drugs are still being tested in clinical trials to see if they are effective against COVID-19. This step is needed to make sure the medications are safe for this particular use and what the proper dosage should be.
So it could be months before treatments are available that are known to work against COVID-19. It could be even longer for a vaccine. But there are still other tools we can use to reduce the damage done by the novel coronavirus.
“Even though technological advances allow us to do certain things more quickly,” Lee told Healthline, “we still have to rely on social distancing, contact tracing, self-isolation, and other measures.”

Searching for Effective Treatments

Drug development is sometimes described as a pipeline, with compounds moving from early laboratory development to laboratory and animal testing to clinical trials in people.
It can take a decade or more for a new compound to go from initial discovery to the marketplace. Many compounds never even make it that far.
That’s why many medications being eyed as potential treatments for COVID-19 are drugs that already exist.
In a recent review in the British Journal of Pharmacology, scientists from the United Kingdom called for wider screening of existing drugs to see if they might work against the coronavirus.
They identified three stages of infection at which the coronavirus could be targeted: keeping the virus from entering our cells, preventing it from replicating inside the cells, and minimizing the damage that the virus does to the organs. Many of the drugs being developed or tested for COVID-19 are antivirals. These would target the virus in people who already have an infection.
Lee says antivirals work better if you administer them sooner, “before the virus has a chance to multiply significantly.” And also before the virus has caused significant damage to the body, such as to the lungs or other tissues.Dr. Robert Amler, dean of the School of Health Sciences and Practice at New York Medical College and a former chief medical officer at the Centers for Disease Control and Prevention (CDC) Agency for Toxic Substances and Disease Registry (ATSDR), says both antivirals and vaccines will be valuable tools in combating COVID-19.
However, he told Healthline that “antivirals are likely to be developed and approved before a vaccine, which typically takes longer.”

Antivirals

Remdesivir: Developed a decade ago, this drug failed in clinical trials against Ebola in 2014. But it was found to be generally safe in people. Research with MERS showed that the drug blocked the virus from replicating.
The drug is being tested in many COVID-19 clinical trials around the world. This includes studies in which remdesivir is being administered alongside other drugs, such as the anti-inflammatory drug baricitinibTrusted Source.
In late April, the drug’s manufacturer Gilead Sciences announced one of its trials had been “terminated” due to low enrollment. Gilead officials said the results of that trial had been “inconclusive” when it was ended. A few days later, the company announced that preliminary data from another trial of remdesivir overseen by the National Institute of Allergy and Infectious Diseases (NIAID) had “met its primary endpoint.”Dr. Anthony FauciTrusted Source, the institute’s director, told reporters the trial produced a “clear cut positive effect in diminishing time to recover.” He said people taking the drug recovered from COVID-19 in 11 days compared to 15 days for people who didn’t take remdesivir. More details will be released after the trial is peer reviewed and published.
Gary Schwitzer, founder of HealthNewsReview.org, though, said that the researchers changed the primary endpoint two weeks before Fauci’s announcement. Schwitzer compared that to moving football goalposts closer to make it easier to get a touchdown.
At the same time, another study published in The Lancet reported that participants in a clinical trial who took remdesivir showed no benefits compared to people who took a placebo. Despite the conflicting results, the FDA issued an order on May 1 for the emergency use of remdesivir.
Kaletra: This is a combination of two drugs — lopinavir and ritonavir — that work against HIV. Clinical trials are being done to see whether it also works against SARS-CoV-2. One small study published May 4 in the journal Med by Cell Press found that lopinavir/ritonavir did not improve outcomes in people with mild or moderate COVID-19 compared to those receiving standard care. Another study, published May 7 in the New England Journal of Medicine, found that the drug combination was not effective for people with severe COVID-19. But another study found that people who were given lopinavir/ritonavir along with two other drugs — ribavirin and interferon beta-1b — took less time to clear the virus from their body. This study was published May 8 in The Lancet.
Favipiravir: This drug is approved in some countries outside the United States to treat influenza. Some reports from China suggest it may work as a treatment for COVID-19. These results, though, haven’t been published yet. Japan, where the medication is made, is sending the drug to 43 countries for clinical trial testing in people with mild or moderate COVID-19.
Arbidol: This antiviral was tested along with the drug lopinavir/ritonavir as a treatment for COVID-19. Researchers reported in mid-April that the two drugs didn’t improve the clinical outcomes for people hospitalized with mild to moderate cases of COVID-19.

Other Treatments

Scientists are also looking at other ways to target the virus or treat the complications of COVID-19. Among them is ibuprofen. In early June, scientists started a clinical trial to see if the pain medication could be used on people hospitalized with COVID-19. Their theory is ibuprofen’s anti-inflammatory qualities could help ease breathing difficulties associated with the illness.

Hydroxychloroquine and chloroquine: These drugs received emergency use authorization from the FDA at the end of March. At that time, manufacturer Novartis donated about 30 million doses of hydroxychloroquine and one million doses of chloroquine to the nation’s Strategic National Stockpile. Clinical results, though, have been, at best, mixed.

In late May, the World Health Organization announced it was halting its clinical trials of hydroxychloroquine due to safety concerns. Around the same time, officials in France, Belgium, and Italy stopped the use of hydroxychloroquine for COVID-19 treatment due to safety concerns.

In early May, the authors of an observational study in the New England Journal of Medicine reported that patients who had been given hydroxychloroquine didn’t benefit. The medication didn’t harm the participants who took it, but the drug also didn’t lessen their need for ventilators or reduce their risk of death.

Another study in JAMA published in May also found that hydroxychloroquine, with or without the antibiotic azithromycin, didn’t help people with COVID-19. Given the scarcity of good data, the authors of an opinion piece in the journal Annals of Internal Medicine questioned the use of these medications. In late April, the FDA issued a warning against the use of both hydroxychloroquine and chloroquine outside of medical facilities. The agency stated there were “serious and potentially life-threatening heart rhythm problems” connected with the drugs.

Monoclonal antibodies: These drugs trigger the immune system to attack the virus. Vir Biotechnology has isolated antibodies from people who survived SARS. The company is working with Chinese firm WuXi Biologics to test them as a treatment for COVID-19.AbCellera has isolated 500 unique antibodies from a person who recovered from COVID-19 and is set to start testing them.
Blood plasma transfers: Along the same lines, the FDA has announced a process for medical facilities to conduct trials on an experimental treatment that uses blood plasma from people who have recovered from COVID-19. The theory is that the plasma contains antibodies that will attack this particular coronavirus. In late March, the New York Blood Center began collecting plasma from people who have recovered from COVID-19. In early June, researchers reported that 19 of 25 people with COVID-19 who were treated with convalescent plasma transfusions at Houston Methodist Hospital in Texas had improved. Eleven of those patients have been released from the hospital.
Stem cells: Athersys Inc. began a phase II/III clinical trial that will examine whether the company’s stem cell treatment could potentially benefit people with acute respiratory distress syndrome (ARDS). This condition occurs in some people with severe COVID-19. Mesoblast has also developed a potential stem cell treatment for ARDS. The company is enrolling people with moderate to severe ARDS into a phase II/III clinical trial in the United States.
Immune suppressants: In some people with COVID-19, the immune system goes into overdrive, releasing large amounts of small proteins called cytokines. Scientists think this “cytokine storm” may be the reason certain people develop ARDS and need to be put on a ventilator. Several immune suppressants are being tested in clinical trials to see whether the drugs can quell the cytokine storm and reduce the severity of ARDS. These include baricitinib, a drug for rheumatoid arthritis; CM4620-IE, a drug for pancreatic cancer; and IL-6 inhibitors. The FDA has also approved a device that filters cytokinesTrusted Source out of the blood of patients.

Next Steps for Treatments

While a lot of the focus is on developing new treatments for COVID-19, improvements in how doctors care for patients using existing technology are also crucial. “The things that we have to worry about with the novel coronavirus is that it can cause pneumonia and acute respiratory distress syndrome,” Lee said. “There are ways of treating those things that can reduce the effects, so doctors are trying to use those as well.”No company has offered a timeline for when its drug might be used more widely to treat COVID-19. This isn’t an easy thing to estimate.
After laboratory and animal testing, drugs have to pass through several clinical trial states before they can be approved for widespread use in people.
It’s also difficult to speed things up because scientists have to enroll enough people in each stage to have useful results. They also have to wait long enough to see whether there are harmful side effects of the drug. However, drugs can sometimes be given to people outside a clinical trial through the FDA’s “compassionate use” program. For this to happen, people must have an “immediately life-threatening condition or serious disease or condition.”Doctors at the University of California, Davis were able to secure this type of approval for a woman with severe COVID-19 to receive remdesivir. They reported she was doing well.
Many will take this as a sign that the drug works. But because the drug was given outside of a clinical trial to just one person, it’s not possible to know for certain. Also, other people may not have the same response to the drug. Improvements in testing can also reduce COVID-19 deaths by slowing the spread of the virus. As cities and states lift stay-at-home and physical distancing orders, increased testing will be needed to prevent large spikes in infections.
The FDA has granted emergency use authorizations for many diagnostic tests for coronavirusTrusted Source. Companies and universities around the world also continue to develop new ones. On May 8, the FDA announced the authorization of the first at-home saliva-based COVID-19 diagnostic test. The test, which was designed by Rutgers Clinical Genomics Laboratory, allows people to spit in a tube at home and mail it back to the Rutgers lab for testing.
This is the first at-home test approved involving saliva collection — all other approved at-home tests are conducted via a nasal swab. The Rutgers test will hopefully expand access to people unable to easily make it to a clinic or drive-by testing facility. The test is currently only available by prescription.
New guidelines were posted by the FDA in early May designed to expedite the development and approval of more at-home self-collection kits to further expand access to testing. Under the new guidance, test developers are encouraged to reach out to the FDA to ensure their kits and shipping methods are in compliance with the most up-to-date regulations.
One commercially-available test developed by scientists in Europe can show in 15 minutes whether someone is infected with coronavirus. The test uses a sample collected with a nasopharyngeal swab inserted into the nose.
A real-world analysis found that the test could detect 6 out of 10 people with coronavirus infection. It performed much better at identifying when an infection was not present. While the test is not 100 percent effective, it doesn’t require special reagents or trained laboratory staff to run. This would make it ideal for health clinics or in low- and middle-income countries with few clinical laboratories. But it would have to be part of a broader testing strategy.

Vaccines

A vaccine is designed to protect people before they’re exposed to a virus — in this case, SARS-CoV-2, the virus that causes COVID-19. A vaccine basically trains the immune system to recognize and attack the virus when it encounters it. Vaccines protect both the person who’s vaccinated and the community. Viruses can’t infect people who are vaccinated, which means vaccinated people can’t pass the virus to others. This is known as herd immunity. Many groups are working on potential vaccines for SARS-CoV-2, with several backed by the nonprofit Coalition for Epidemic Preparedness Innovations (CEPI).
There are more than 100 projects around the world centered on the development of a vaccine for the coronavirus. As of May 11, eight candidate vaccines were being tested in clinical trials in people. An official at the National Institutes of Health said in mid-May that large-scale testing could begin in July with a vaccine potentially available by January. Other experts say the more likely timeline is summer or fall of 2021. Here’s a look at some of the projects:
  • Moderna:  In March, the company began testing its messenger RNA (mRNA) vaccine in a phase I clinical trial in Seattle, Washington. In mid-May, the company announced the vaccine had produced antibodies in all 45 trial participants in this initial clinical phase. The study included 45 healthy volunteers, ages 18 to 55, who are getting two shots 28 days apart. The company has developed other mRNA vaccines before. Those earlier studies showed that their platform is safe, which allowed the company to skip certain animal testing for this specific vaccine. In early May, the company received permission from the FDA to start a phase II study of its vaccine. The company expects to begin a phase III clinical trial in July. The FDA also agreed to fast-track regulatory review of this vaccine if it succeeds in a phase III clinical trial.
  • Inovio: When COVID-19 appeared in December, the company had already been working on a DNA vaccine for MERS, which is caused by another coronavirus. This allowed the company to quickly develop a potential vaccine for SARS-CoV-2. Company officials announced at the end of April that it had enrolled 40 healthy volunteers in its phase I clinical trial. It is preparing to start a phase II/III clinical trial this summer.
  • University of Oxford in England: A clinical trial with more than 500 participants began in late April. Oxford officials said the potential vaccine has an 80 percent chance for success and could be available as early as September. The vaccine uses a modified virus to trigger the immune system. The university has partnered with pharmaceutical company AstraZeneca. The company reported in mid-May the vaccine was effective against COVID-19 after it was given to six rhesus macque monkeys. The company expects to begin a late-stage clinical trial by the middle of this year. Officials said in mid-May that if the clinical trial is successful, they could deliver 30 million doses by September.
  • University of Queensland in Australia: Researchers are developing a vaccine by growing viral proteins in cell cultures. They began preclinical testing stages in early April.
  • Pharmaceutical companies: Johnson & Johnson and Sanofi are both working on a vaccine of their own. Pfizer has also teamed up with a German company to develop a vaccine. Their initial clinical trial with 200 participants was given the green light in late April. The two companies began human testing in the United States in early May.
Advances in genetic sequencing and other technological developments have sped up some of the earlier laboratory work for vaccine development. However, Fauci told reporters in March that a vaccine won’t be available for widespread use for at least another 12 to 18 months. This is the timeline to complete the phase III clinical studies. Fauci wrote in the journal Science in May that multiple successful vaccines may be needed to meet the demand of vaccinating billions of people worldwide.

Speeding Up Vaccine Development

Some scientists argue that a “human challenge trial” could speed up the vaccine clinical trials — potentially shaving months off the timeline.
In this type of trial, healthy volunteers are given a potential vaccine and then intentionally infected with the coronavirus. Usually, researchers wait for a person given a test vaccine to contract the virus naturally. Then they look at how well the person was protected by the vaccine.
There are no plans for this kind of study in the United States, but more than 16,000 people in more than 100 countries have signed up to take part. A human challenge trial raises many ethical questions. One is that there’s still a lot we don’t know about the coronavirus, including who will get very ill or die from COVID-19. That means people can’t really know the risks of participating in the study, so they wouldn’t be able to give high-quality informed consent. This is an essential part of modern clinical trials.
Given the scope of the pandemic, though, some experts think this type of trial will happen eventually. In preparation for this, the World Health Organization recently released ethical guidelines to navigate these tricky waters. Meanwhile, some clinical trials are underway in the Netherlands and Australia to see whether existing vaccines for tuberculosis might also protect against SARS-CoV-2.
The polio vaccine is another possible option. Scientists think these vaccines might boost the immune system just enough to fight off the new coronavirus, although there’s no evidence yet to confirm this theory.
There’s no guarantee any of the vaccine candidates will work. “There’s a lot of uncertainty with vaccine development,” Lee said. “Naturally, you have to make sure the vaccine is safe. But you also have to make sure the vaccine will elicit enough of an immune response.”Like drugs, potential vaccines have to pass through the same clinical trial stages. This is especially important when it comes to safety, even during a pandemic.“The public’s willingness to back quarantines and other public-health measures to slow spread tends to correlate with how much people trust the government’s health advice,” Shibo Jiang, a virologist at Fudan University in China, wrote in the journal NatureTrusted Source.“A rush into potentially risky vaccines and therapies will betray that trust and discourage work to develop better assessments,” he said.

Clinical Trial Stages

  • Phase I: The drug is given to a small number of healthy people and people with a disease to look for side effects and figure out the best dose.

  • Phase II: The drug is given to several hundred people who have the disease, looking to see whether it works and if there are any side effects that weren’t caught during the initial testing.

  • Phase III: In this large-scale trial, the drug is given to several hundred or even up to 3,000 people. A similar group of people take a placebo or inactive compound. The trial is usually randomized and can take 1 to 4 years. This stage provides the best evidence of how the drug works and the most common side effects.
  • Phase IV: Drugs that are approved for use undergo continued monitoring to make sure there are no other side effects, especially serious or long-term ones.

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