Every day, researchers work to develop safe, effective therapies for a variety of diseases. That work is especially in the spotlight during the fight against SARS-CoV-2, the virus that causes COVID-19. One promising treatment involves monoclonal antibodies (mAbs).
UCLA Health researcher and infectious disease specialist Kara Chew, MD, MS, is helping to develop a monoclonal antibody therapy for COVID-19 through a clinical trial. She explains how mAbs might be used to prevent complications and worsening of the disease.
What are monoclonal antibodies?
Antibodies are an essential component of our immune system. They form when foreign cells, such as bacteria and viruses, enter the body:
- These foreign bodies release or have on their surface substances called antigens.
- The antigens bind to certain types of white blood cells known as B lymphocytes (or B cells).
- It’s this bond between antigen and B cells that triggers the body to secrete antibodies.
- Antibodies are proteins that seek out and block the foreign invader from spreading. Antibodies also stimulate other arms of the immune system to fight it.
“Monoclonal antibodies are synthetic antibodies manufactured in a lab using the natural antibody as a model,” says Dr. Chew. “The model antibodies are selected because they can home in on a specific region of a foreign or threatening cell to prevent it from causing harm. Scientists then replicate the antibody to turn it into a treatment.”
How can mAbs be used in the fight against COVID 19?
“The mAbs bind to the spikes (proteins) on the SARS-CoV-2 virus,” says Dr. Chew. “By binding to that protein, the virus cannot infect cells and replicate. As a result, mAbs may prevent COVID symptoms from worsening.”
Monoclonal antibody therapy for COVID-19 is not yet widely available, but it is being actively studied. The study Dr. Chew is involved in, called ACTIV-2, is exploring the effectiveness of mAbs for people who have tested positive for COVID-19 and have symptoms, but aren’t so sick that they require hospitalization. The study will examine several different mAbs and other drugs simultaneously. It is currently studying one made by the pharmaceutical company Lilly.
“When people sign on to participate, they will receive a one-time infusion,” says Dr. Chew of her trial. “Though it’s given just once, the treatment lasts for several weeks. Clinicians will follow the volunteers and track symptoms closely for the first 28 days through at-home or in-clinic visits.”
The U.S. Food and Drug Administration, on October 22, approved its first treatment for COVID-19. The antiviral drug Veklury (remdesivir) is for use on adults, as well as children age 12 or older and weighing at least 88 pounds, who require hospitalization for the virus.
“For people who aren’t sick enough to be hospitalized, we currently have no treatment options that target the virus directly,” says Dr. Chew. “We advise people who test positive to isolate at home and treat their symptoms, but we have no way of preventing the virus from progressing. It’s a waiting game to see if or when the person will become sick enough to need hospitalization. Through this trial, we have the potential to prevent COVID-19 from progressing — and ultimately save lives.”
Monoclonal antibody therapy: Where is it headed?
The monoclonal antibody currently being studied is in phase 2 of a three-phase process. Phase 2 aims to determine whether the treatment is safe and potentially effective enough to test on more volunteers. Researchers look to prove efficacy with these measures:
- Shorter duration of symptoms
- Loss of detectable virus with a nasopharyngeal swab
- Maintained blood oxygen levels
“For phase 2, we need roughly 220 volunteers for each new drug that enters the trial. Half of them will receive the mAbs and the other half will receive a placebo,” says Dr. Chew. “Because of the importance of COVID-19-related research and the design of the study, we can move to phase 3 for each drug as soon as we have enough data to show safety and suggest effectiveness.”
Phase 3 of the study will involve an additional 890 volunteers to receive the treatment and 890 to receive the placebo. The goal is to prove that mAb treatments reduce hospitalization and deaths.
“The research is funded by Operation Warp Speed, the U.S. government’s effort to speed up the development of treatments and vaccines for COVID-19, and under the umbrella of the National Institutes of Health’s ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines),” says Dr. Chew. “ACTIV is a public/private partnership to take on the coronavirus in a coordinated way.”
Researchers are targeting 100 sites across the globe. Currently, more than 30 sites are activated in the U.S., including UCLA Health.
If you recently tested positive for COVID-19 and have symptoms, you may be eligible to participate in the ACTIV-2 study. If you experience symptoms of COVID-19 but have not received a test, contact your primary care provider.
