Georgia CTSA CPTR Graduate's Anti-Inflammatory Drug Selected for International Phase 3 COVID-19 Trial

"What we have learned about inflammation for HIV is a foundation for streamlined effective approaches towards other diseases and viral infections including COVID," says Dr. Christina Gavegnano.

Christina Gavegnano, PhD, Assistant Professor, Emory University School of Medicine, and Georgia Clinical & Translational Science Alliance (Georgia CTSA) Certificate Program in Translational Research (CPTR) graduate, has been working with Baricitinib for the indication of HIV and shares the internationally issued patent for use for viral infections. Baricitinib has been selected by the National Institutes of Health (NIH) for a multi-country phase 3 study for COVID-19 treatment.

"We discovered this class of drugs, which are called Jak 1/2 inhibitors, had efficacy against HIV due to its anti-inflammatory properties and in some cases direct-acting antiviral effects as well. I was a student in the Georgia CTSA CPTR program several years ago when I was a graduate student. Now I'm an Assistant Professor at Emory, and the CTPR program has provided a solid foundation for me to be able to take drugs from the bench to the bedside in a literal sense; now we have done a multisite phase 2 with the NIH sponsored AIDS Clinical Trial Group with this class of drugs for HIV, and we are now in an international phase 3 study in over 65 countries for COVID-19 with Baricitinib. We’ve done extensive work with Baricitinib showing that it has efficacy for HIV, reverses neurocognitive impairment conferred by HIV, and also reduces the HIV reservoir. Now we’re seeing that it has additional efficacy against COVID. A group in London published a paper on artificial intelligence in The Lancet predicting that our drug would have great efficacy for COVID not only because of the anti-inflammatory properties but also it would be a potent inhibitor of key events that facilitate fusion and entry of COVID into host cells. Artificial intelligence met reality and provided great utility for our ability to help initiate the phase 3 clinical trial," comments Gavegnano.

The NIH selected Baricitinib, made by Eli Lilly, from over 25 drugs to use in a combination study with Remdesivir for the international phase 3 study that is already underway in many countries including the U.S. with several sites in Atlanta. There is also another phase 3 study in Canada and one in Italy. Several additional countries now have opened clinical studies for the indication of COVID.

"Vince Marconi, MD was the clinical PI for our HIV work and has been our clinical counterpart. Dr. Marconi and his team prescribed and administered Baricitinib for compassionate use to 15 patients in Atlanta with severe disease COVID. All 15 patients recovered and were eventually discharged. The study was not placebo controlled, and therefore warranted controlled clinical study, which is now underway. These data are submitted for publication currently.  Further, the recovery upon Baricitinib treatment was hallmarked by a decrease in markers of the ‘cytokine storm’ that has been shown to drive disease progression. At the same time, this drug has been predicted with artificial intelligence to demonstrate direct-acting antiviral activity.  Certainly, more work must be done to tease out the exact mechanisms of this agent," says Gavegnano. "A group from Italy who also read The Lancet paper prescribed Baricitinib to 12 patients with mild and moderate disease who were not ventilated, and they all also recovered. These publications are now starting to come out showing that the drug has great efficacy in humans. We are hopeful that the phase 3 study now in a controlled setting with appropriate arms will be able to provide the answers."

Dr. Vincent Marconi remarks, "My involvement with this class is owed to Christina and Ray (Raymond Schinazi, PhD) almost 8 years ago. We have worked very closely on clinical studies of this class for people with HIV, so were not surprised when this class was being considered as treatment of the cytokine release syndrome for COVID-19.  After seeing the results of the in silica study of Baricitinib against SARS-CoV-2, we were more encouraged to move ahead with clinical studies in light of how critical the situation had become in hospitals worldwide. This led us to explore off-label and clinical trial studies."

Gavegnano adds, "Sharing is key. Anyone who has worked on this class of drugs, even if it’s for another indication, knows it’s extremely important that we communicate our findings with each other. The findings for HIV are not in a silo; they have direct overlap towards understanding about the utility for COVID. Talking among each other and sharing what we already know in HIV has provided a strong foundation for our ability to move forward. Keeping the lines of communication open across viruses for people who have worked on this class of drugs is paramount. This is something our team has worked on for about 10 years for HIV, but it’s taken on a new exit ramp as it relates to this particular pandemic."

"Inflammation drives many things. We’re just beginning to pull back the covers to understand how important inflammation is for disease pathology. Inflammation holds the key to the immune system and being able to discern how and when you should control that says a lot about if you can treat someone successfully. As a whole, inflammation is a key driver of disease progression. We probably didn’t realize how much until we began to look at it for viral infections."

Gavegnano shares how the Georgia CTSA Certificate Program in Translation Research has guided her work, "I was drawn to the Georgia CTSA CPTR because of the ability to build a bridge from the bench to the clinic. I’ve always had a great interest in drug discovery and not letting drug discovery be the end, but instead the beginning. This program is a wonderful way to bridge the beginning to the end. For every person who is involved in drug discovery, it’s your dream for your drug to be used in the clinic. It’s a special moment when you know people are taking something that you invented. It doesn’t happen every day; it happens only a handful of times in your life if you’re lucky. Being able to know how to build that bridge properly is something that is especially highlighted in the CPTR program."

The Certificate Program in Translational Research (CPTR) is a formal 16-credit Emory Laney Graduate School program for trainees who seek to conduct research at the interface between basic and translational science and clinical medicine. The CPTR enhances and transforms translational research training for predoctoral PhD and PharmD students, postdoctoral fellows, and junior faculty at Emory, MSM, Georgia Tech, and UGA College of Pharmacy.

The Georgia CTSA is a statewide partnership between Emory, MSM, Georgia Tech, and UGA and is one of over 60 in a national consortium striving to improve the way biomedical research is conducted across the country. The consortium, funded through the National Center for Advancing Translational Sciences (NCATS) and the National Institutes of Health's Clinical and Translational Science Awards, shares a common vision to translate laboratory discoveries into treatments for patients, engage communities in clinical research efforts, and train the next generation of clinical investigators. For more information, visit GeorgiaCTSA.org.