Monoclonal antibodies are complex and expensive to produce, meaning poor countries might be priced out.
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As the race to develop a vaccine against COVID-19 rages on, some researchers are focused on a short-term way to treat people with the disease: monoclonal antibodies. Rather than wait for vaccines to coax the body to make its own antibodies, these scientists want to inject designer versions of these molecules to directly disable the SARS-CoV-2 coronavirus. But mass-produced antibodies, routinely used to treat diseases such as cancer, are complex to manufacture and come with a hefty price tag. That risks placing them beyond the reach of poor countries.
That warning comes from a report released on 10 August by two leading public-health charities: the International AIDS Vaccine Initiative (IAVI), a non-profit research organization in New York City, and Wellcome, a research funder in London. It calls for boosting the global availability of therapeutic antibodies against COVID-19 and other diseases by developing regulatory pathways, business models and technologies to lower the cost of the pricey medicine.
It is a tall order, acknowledges Mark Feinberg, president of IAVI. “But COVID-19 really forces the issue in a major way,” he says. “The pandemic demands that this dialogue take place, and that solutions for this challenge be created.”
A vaccine against COVID-19 is likely still months away, and it will be months after that before many people are able to receive it. Even then, some people, including the elderly, might not respond strongly to immunization, and others may refuse it altogether.
Those factors make it important to develop therapies against COVID-19. Physicians still don’t have many ways to treat the disease. The antiviral remdesivir has been shown to shorten hospital stays for some patients, but it is expensive and in short supply. And a steroid called dexamethasone, which is cheap and widely available, has been shown to benefit only people with severe infections.
So scientists are increasingly focusing on monoclonal-antibody drugs in the hope that they will harness the immune system’s natural response to viral invaders, says Jens Lundgren, an infectious-disease physician at the University of Copenhagen and Rigshospitalet, one of the city’s hospitals. “The science around this has been exploding,” he says. “It’s very compelling.” Lundgrenis leading a large, multinational trial of an antibody developed by Eli Lilly in Indianapolis, Indiana; AbCellera in Vancouver, Canada; and the US National Institutes of Health (NIH).
In this approach, researchers isolate antibodies from recovering patients and identify those that best ‘neutralize’ the virus by binding to it and keeping it from replicating. They then produce these antibodies in bulk in the laboratory. If the treatment is found to be effective, companies will scale up production, using cells grown in giant bioreactors.
This differs from ‘convalescent plasma’ treatments, composed of a complex mixture of antibodies and molecules taken directly from the blood of people recovering from COVID-19 and used to treat other patients. The effects of both of these approaches are short term: neither type of treatment will produce a long-lasting immune response.
IAVI estimates that more than 70 antibody therapies are being developed to treat and prevent COVID-19, and several clinical trials are underway.
But past experience suggests that if such treatments are developed against COVID-19, they might not find their way to much of the world. Monoclonal-antibody therapies are generally more expensive to make than small-molecule drugs are, they must be injected rather than taken orally and they are difficult for generic-drug makers to duplicate. About 80% of global sales of licensed therapeutic antibodies — which treat autoimmune diseases, among other ailments — are in the United States, Europe and Canada. The median price for antibody therapies in the United States is US$15,000–$200,000 per year of treatment, according to the IAVI–Wellcome report.
Feinberg says that the pandemic could spur technological innovation to find easier and cheaper ways to make large quantities of antibodies. It could also prompt business arrangements between the companies that develop therapeutic antibodies and other manufacturers — akin to the makers of generic versions of small-molecule drugs — that could try to copy the process and distribute the drugs more widely. And it might force regulators in low- and middle-income countries to become more familiar with antibody therapies and better able to approve their use.
“I don’t know that any one of those will provide the solution,” says Feinberg. “But if you combine them, then hopefully you’ll have significant synergy.”
No one has yet completed a large, randomized study of an antibody therapy against COVID-19, but results from such trials are expected in the coming months. Lundgren’s trial, announced on 4 August, aims to enrol 1,000 people with COVID-19. Another large trial, sponsored by the NIH and Regeneron, a biotechnology company in Tarrytown, New York, launched on 6 July and will test a cocktail of two antibodies against SARS-CoV-2. Results are expected in late September.
Although these antibodies all target the same virus, each interacts with SARS-CoV-2 differently: some will bind more strongly to the virus than others, for example, or will target sites on its surface that shut the virus down more efficiently. And although antibodies are a natural means of defence, there are safety concerns, Lundgren notes. Researchers will be looking out for signs of “antibody-dependent enhancement”, a troubling phenomenon in which some antibodies can help viruses to gain entry into human cells, rather than prevent infection. Although there are no signs yet that this will be the case for SARS-CoV-2, a large trial is needed to convincingly settle the matter, Lundgren says.
If those hurdles are cleared and the antibodies prove effective, it will be a matter of manufacturing enough and distributing them to a world in crisis. As with other new therapies and medical technologies, the access gap will not just be between rich and poor countries, cautions Eduardo Cazap, president of the Latin American and Caribbean Society of Medical Oncology in Buenos Aires. “You have underserved populations in rich countries and also wealthy populations in poor countries,” he says. “This is a global issue.”