“We had all of that information and background data and government funding to go into human testing for influenza and bam, coronavirus emerges out of Wuhan,” said David Perryman, COO of DRIVE.
Currently, there are no approved medications to treat or vaccines to prevent the novel coronavirus, which causes the disease COVID-19. As the virus has spread worldwide, infecting more than 212,000 people and killing at least 8,727, researchers have scrambled to come up with therapies.
On Thursday, President Trump said he directed the Food and Drug Administration to see whether hydroxychloroquine, a drug used for malaria patients, could be used to treat COVID-19. He said the drug could be made available almost immediately, though it hasn’t been approved by the FDA for the novel coronavirus and studies about its effectiveness are still underway.
Emory is among the Georgia-based universities and companies in the race to find a vaccine or treatment for the virus. Experts at Smyrna-based GeoVax Labs are working on a vaccine, as are researchers at the University of Georgia in cooperation with EpiVax. Japan’s Takeda Pharmaceutical Co. said it is working on a plasma-derived therapy for high-risk individuals and that it would begin producing the therapy in a segregated area of its Georgia manufacturing facility.
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The ability to rapidly bring any treatment or vaccine through clinical testing and to the market will depend in large part on access to funding, though. The review process with the FDA involves a dozen steps including pre-clinical animal testing and three phases of human testing. The median estimated cost of a clinical trial for a new drug is $19 million, with the highest estimated trial cost at $347 million, according to data in a 2018 JAMA Internal Medicine Study.
Emory launched a GoFundMe to help accelerate testing of its antiviral drug, while David Dodd, chairman and CEO of GeoVax traveled to Washington, D.C. last week to meet with members of Congress about the $8.3 billion in emergency coronavirus spending that President Trump approved earlier this month. About $3 billion of that spending is designated for research and development of treatments and vaccines. Dodd said it was unclear when funds would be disbursed.
FDA Drug Review Steps
The FDA says it is working with vaccine developers and other researchers and manufacturers to help expedite the development and availability of medications to treat and prevent COVID-19. However, even with an expedited program, developers must demonstrate the safety and effectiveness of therapies. The typical approval process involves these steps:
Preclinical testing conducted on animals
Investigational new drug application outlines what the sponsor of a new drug proposes for human testing in clinical trials
Phase 1 studies (20 to 80 people).
Phase 2 studies (a few dozen to 300 people).
Phase 3 studies ( several hundred to 3,000 people).
FDA and drug sponsors may meet before a new drug application (NDA) is submitted.
NDA submitted to formally ask the FDA to consider a drug for marketing approval.
The FDA has 60 days to decide whether to file the NDA so it can be reviewed.
If the FDA files the NDA, a review team is assigned to evaluate the sponsor’s research on the drug’s safety and effectiveness.
The FDA reviews information that goes on a drug’s professional labeling (information on how to use the drug).
The FDA inspects the facilities where the drug will be manufactured as part of the approval process.
FDA reviewers will approve the application or issue a complete response letter.
Source: U.S. Food and Drug Administration
“The sooner we receive notification of funding commitments, the sooner we can accelerate testing,” Dodd said. “The advantage is for a larger entity, but sometimes the innovation is from a smaller company.”
Researchers at Emory’s Drug Innovation Ventures have focused on developing broad spectrum drugs that could work against different species of viruses. EIDD-2801 was on the verge of entering clinical tests for treatment of influenza, but based on the drug’s activity against the coronaviruses Middle East Respiratory Syndrome (MERS) and severe acute respiratory syndrome (SARS) in animal testing, researchers thought it would be a good candidate for novel coronavirus as well. The drug, which would be available in pill form, works by mimicking the building blocks of the virus’ genetic code. When the virus tries to reproduce with the false building blocks, it accumulates too many mutations and dies.
Getting over the funding hurdle has been a challenge. “When something emerges and the money is not already deployed, it takes time for the money to be deployed,” Perryman said. The nonprofit is seeking $5 million on its GoFundMe campaign, but only about $32,000 has been raised so far.
David Perryman is chief operating officer for Drug Innovation Ventures at Emory. He previously was CEO and founder of a biotech company.
One way to reduce the time and money traditionally involved in clinical testing of drug treatments is to find a new application for an existing drug, and university researchers are also working on applying an existing anti-inflammatory drug to treat COVID-19.
In February, a scholarly paper in the medical journal The Lancet proposed using the anti-inflammatory drug Baricitinib to fight novel coronavirus. The drug, which is being reviewed for the new application by Emory professor Christina Gavegnano, has been FDA approved for the treatment of rheumatoid arthritis since 2018.
Patients with novel coronavirus have two main issues, the virus rapidly reproducing then possibly moving into the lungs where it can cause inflammation. Baricitinib could also be used along with traditional antivirals to eliminate residual inflammation, researchers believe.
“We are currently testing Baricitinib in the lab and highly optimistic about its ability to block replication of the virus and eliminate inflammation that the virus causes which drives lung damage,” Gavegnano said.
In addition to these efforts, Emory is one of the sites hosting clinical trials for Remdesivir, the potential COVID-19 treatment that is farthest along in testing. Remdesivir, an IV treatment developed by pharma heavyweight Gilead Sciences Inc., was the first drug to land in the spotlight for treating COVID-19. It had previously been tested in Ebola-infected humans with disappointing results but showed more promise in animal models to treat coronaviruses, including MERS and SARS.
The view through a microscope at Smyrna-based GeoVax of one of the vaccine candidates for COVID-19 that the lab is working on. Bob Andres / email@example.com
The drug is now in clinical trials at up to 75 sites around the world including Emory and is being tested on hospitalized individuals who are infected with novel coronavirus and have moderate or severe disease.
Clinical trials for Remdesivir are adaptive, meaning that once a potential drug is deemed inferior, it is removed from the trial and the superior drug is tested against the next best option. Remdesivir is currently being compared to standard care for viral pneumonia, said Aneesh Mehta, principal investigator at Emory, but there is not enough data yet to evaluate the drug’s efficacy.
“The scientific community across the board is engaged on how to care for patients and communities facing COVID-19,” Mehta said. “A lot of therapeutic agents are bringing value. We should not put all our eggs in one basket.”
To help speed up development of COVID-19 treatments, the FDA has been working closely with drug sponsors, according to a spokesman for the FDA. That has included expediting initial reviews to allow clinical trials to begin as soon as possible.
Even with the sense of emergency created by a pandemic, it can take up to 18 months to develop a vaccine for a virus. GeoVax One believes it can trim six months from the process without compromising safety.
It began developing three coronavirus vaccines in January which are ready for animal testing, Dodd said. The vaccine duplicates the outer shell of the virus without the infectious element, causing a strong immune response in the patient with no risk of infection.
With the safety well known and validated, GeoVax can move forward with more speed, he said.
Dodd and other developers hope this experience with novel coronavirus demonstrates the need for the continued development of effective vaccines and treatments even after a perceived threat passes.
“We have to do a better job on our end letting people know pathogens are going to continue,” said Ted Ross, Director of the Center for Vaccines and Immunology at the University of Georgia. Ross is collaborating with EpiVax to design a vaccine for COVID-19 which is currently being tested on animals.
The future, he said, will require a response that is more forward thinking. “We need better types of technology that will deal with a strain of a pathogen that we don’t even know exists,” Ross said. “We need that instead of doing whack-a-mole after each outbreak.”