MANILA — There is increasing interest in antibody-based treatments as the world continues to search for a cure to COVID-19. Countries like the United States are investing millions of dollars to help advance research and development on some of these therapies, including those involving monoclonal antibodies.
Just last week, the Biomedical Advanced Research and Development Authority awarded Regeneron Pharmaceuticals over $450 million — the largest award it has given to one company working on a COVID-19 treatment — to support the advance manufacture of the company’s investigational antibody-based treatment that uses a combination of two monoclonal antibodies. The goal is to ensure the availability of large doses of the treatment, if and when clinical trials are able to show its efficacy.
Doctors closely follow the research on vaccines and therapeutics against COVID-19. But what do they do in the absence of solid evidence of drug efficacy and safety?
There are also other monoclonal antibody-based treatments in development, or under planned clinical trials. Close to 40 studies, mostly in the U.S. and Europe, are currently registered on ClinicalTrials.gov looking into the use of monoclonal antibody therapies for COVID-19.
What is it? And why the interest in this treatment?
The human immune system produces antibodies in response to harmful, foreign substances. But not all of these antibodies would be able to prevent an infection spread. In the case of SARS-CoV-2 — the virus causing COVID-19 — what’s critical, is finding the specific antibody or antibodies that would block the virus from entering the human cell.
Under a monoclonal antibody-based therapy, that specific antibody, referred to as a neutralizing antibody, is replicated in large quantities in the laboratory and administered to patients intravenously. The idea is that it will be much more potent — than giving a broad range of antibodies — in blocking SARS-CoV-2 and preventing it from replicating, said Candela Iglesias Chiesa, founder and director at Global Health Advisors and COVID-19 taskforce lead for Women in Global Health Norway.
It’s called “monoclonal” because the process clones numerous copies of a specific antibody targeted to protect a person from infection, she said.
Nick Cammack, lead of the COVID-19 Therapeutics Accelerator at Wellcome, told Devex that the interest in the therapy for COVID-19 “is predicated on the direct specificity for the virus and the known safety of monoclonal antibody therapies in general.”
This therapy also has a potentially shorter timeline from development, testing to approval compared to chemical-based drugs, Francis Collins, director of the U.S. National Institutes of Health, wrote in a blog post in May.
How effective is it against COVID-19?
There is no evidence of effectiveness yet, but a few clinical trials are planned or underway. Researchers are closely following the investigational therapies by Regeneron and Eli Lilly.
Eli Lilly launched phase 1 studies of two of its investigational monoclonal antibody-based treatments for COVID-19 last month, referred to as LY-CoV555 and JS016. Both are evaluating the safety of the treatment but on different sets of participants. LY-CoV555 is being tested in hospitalized COVID-19 patients, while JS016 is being tested for safety in healthy volunteers.
Meanwhile, Regeneron’s double monoclonal antibody treatment, REGN-COV2, is currently under several trials. The cocktail therapy is in two phase 2/3 clinical trials for COVID-19 treatment, and one phase 3 trial as a COVID-19 prevention therapy.
“Our primary objective is to understand the safety and treatment value of monoclonal antibodies and to that end, we are following the progress of the frontrunners from companies such as Regeneron & Lilly, and then validate that output as data from other monoclonal antibodies is revealed,” Cammack said.
There are other monoclonal antibody-based treatments used and approved for other conditions, such as rheumatoid arthritis, that are also under study for their potential therapeutic value in patients with COVID-19. This includes tocilizumab and sarilumab. But these work differently to other treatments. In some COVID-19 patients, there is an overreaction of the immune system, leading to severe inflammation in the lungs. Due to this, these treatments are being tested to see whether they help reduce the inflammatory response to SARS-CoV-2 — instead of blocking the virus — to improve patient outcomes.
However, a phase 3 trial of sarilumab in critical COVID-19 patients in the U.S. was stopped early July, after 80% of patients that received the treatment experienced adverse side effects.
What are the potential challenges?
One of the potential challenges of having monoclonal antibody-based therapies is the ability to produce them in large quantities. Dr. Daniel Skovronsky, Eli Lilly’s chief scientific officer, told Reuters in June that manufacturing capacity for this kind of therapy is limited, noting that if treatment requires two antibodies, “half as many people will get treated.”
Global Health Advisors’ Chiesa said: “I think the first thing people are thinking about [monoclonal antibodies] is for treatment, because then you would not need as much, right? In prophylaxis, you need it for all the people who are not infected, and in treatment, you just need it for a certain few who are infected or have severe disease and so on.”
Another potential limitation, or question, is the treatment’s bioavailability, she said. Normally, monoclonal antibody therapies are injected through the bloodstream.
“We know that the most important parts of the infection of coronavirus happens in the lungs … So how much of that antibody that you inject into the bloodstream will actually make it to the place where most of the infection is playing out, which would be the lungs,” she continued.
Then there’s the cost. It’s too early to know how much such treatments will be priced — if they end up being effective in treating COVID-19 patients — and how global initiatives to ensure equity to COVID-19 treatments will affect those discussions.
Experts Devex has spoken to argue that monoclonal antibody treatments for cancer, for instance, run in the thousands of dollars. The annual price of these treatments for cancer and hematologic disorders was at $100,000, according to a study published in the American Journal of Managed Care in 2018.