Antibodies are the proteins the body makes to fight infection.
Since the Victorian era, scientists have harnessed this natural protection for treatments.
During the 1918 flu pandemic, doctors proved convalescent plasma — antibody-filled blood plasma from patients who recovered from the disease — could fight flu. Convalescent plasma has been used to treat severe flu, MERS and SARS and now some US doctors are starting to see some success treating Covid-19, too.
Since there isn’t enough donated plasma to treat all patients, modern medicine can fill in the gaps and maybe even improve the process. Scientists can create what are called monoclonal antibodies: lab-made antibodies created specifically to target an infection.
Vaccines have the advantage of working longer than an antibody treatment. Antibody therapies potentially last a month or two and then wear off, but they can be used to temporarily protect vulnerable populations such as nursing home residents or healthcare workers or people with chronic conditions. The therapies could also treat people who are already sick with Covid-19.
Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and a member of the White House coronavirus task force, said these therapies will be essential in the fight against Covid-19.
“Right now we have a major push on a program to develop monoclonal antibodies, convalescent plasma, and hyperimmune globulin, all of which are founded on the same principle of using an antibody that is directed against the virus for either prophylaxis or treatment,” Fauci said in an interview with JAMA on June 8. “I think you’re going to see it’s going to be for both. We’d like to have available for those who are at risk—the elderly and those with underlying conditions—either monoclonal antibodies or convalescent plasma. That’s a very, very high priority.”
Currently there are at least 102 Covid-19 antibody treatments in various stages of development, according to David Thomas, vice president of Industry Research at BIO, the trade association representing the biotechnology industry. Thomas does the research that goes into his organization’s Covid-19 therapeutic development tracker. He said there are so many treatments under development, it’s hard to keep up.
“I never looked at it to grow this big, this fast, and I’ve worked on all different therapeutic areas from Alzheimer’s to cancer, and to see a pipeline of this size and this breadth is amazing,” Thomas said.
Thomas said some therapies are designed to treat the secondary effects of Covid-19 such as inflammation. Others are being designed to kill the coronavirus itself.
Compared to other diseases, the research and development of Covid-19 treatments are moving at “light speed,” Thomas said.
Four monoclonal antibody treatments made to treat and possibly even prevent Covid-19 infection already went into human trials in June.
Indianapolis-based pharma giant Eli Lilly has two. One was developed in collaboration with AbCellera, a biotechnology company based in Canada. Another was developed with Junshi Biosciences.
The antibody Lilly developed with AbCellera called LY-CoV555 is now in a Phase 2 clinical trial of non-hospitalized patients. That study is currently enrolling patients. Lilly said in the future it will also test additional antibodies and experiment with different combinations to see which work best.
Regeneron is testing its antibody cocktail in patients in the US. The New York-based biotech company is enrolling hospitalized and ambulatory patients with Covid-19 in the initial safety/virology phase of the trial, spokesperson Alexandra Bowie said this week. The company hopes to have preliminary data in the next one to two months. They are scaling up manufacturing to create hundreds of thousands of doses by August 2020, dedicating their entire manufacturing plant in upstate New York to the effort.
There is also another effort from Tychan, a biotech company based in Singapore, that has launched a Phase 1 clinical trial in hospitalized patients there. The company said this part of the trial will take about six weeks.
It’s likely, if all goes well in the first phrases of the trials, therapies could advance to the next phases sometime this summer, the companies said, and treatments could potentially be available by the fall. Although, some scientists say, not everything works as planned in real life.
“Sometimes antibodies that work in the lab and neutralized really well aren’t as effective when they are used in animal models or humans, so it’s always a little bit tricky,” said Phyllis Kanki, a professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health. Sometimes it can take time to get the antibody cocktail right, Kanki said.
However, Thomas of BIO,said the industry has built up a lot of antibody therapy development expertise over the years in creating treatments to fight cancer and autoimmune disease.
In addition to therapies specifically designed to fight the novel coronavirus, companies are also looking to repurpose some of their existing monoclonal antibody treatments as potential Covid-19 treatments.
Novartis, for example, is in a phase 3 trial of the drug canakinumab against coronavirus. This interleukin-1beta blocker is FDA-approved to treat certain rare types of periodic fever syndromes, also called auto-inflammatory syndromes.
The company hopes canakinumab can be used to treat patients whose Covid-19 infection has caused a condition called cytokine release syndrome, or cytokine storm. where the body’s immune system overreacts to the infection and harms the body. That trial is currently enrolling patients in the US.
China-based biotech company I-Mab said it also hopes to have the results by August from its trial of an antibody therapy, which it is currently testing on cytokine storm patients, so it could potentially offer a treatment by early fall.
Humanigen’s lenzilumab also seems to be working against cytokine storms, according to a small study from scientists at the Mayo Clinic. That Phase 3 trial is ongoing.
Several other therapies are still being tested in the lab. A South Dakota company, SAB Biotherapeutics, said it plans to start human trials with its antibody treatment derived from the plasma of cattle in July.
Most experts think that the world could have an antibody treatment sooner than a vaccine, although vaccine development is moving along at a record pace, too.
“There’s a lot of excitement around what these antibody therapies can do, at the animal level anyway,” Thomas said. “They were showing neutralizing activity and we’re seeing a lot of positive data.”