The Race To Keep Antibody Treatments One Step Ahead Of Covid-19 Variants


Antibody therapies have been a key tool in keeping patients out of hospitals, but drug companies are fighting to stay ahead of coronavirus mutations.

Last year, as the Covid-19 pandemic raged across the country, filling hospitals beyond capacity, biotech companies raced to develop new treatments and vaccines. Pharma company Eli Lilly, for example, partnered with Vancouver-based AbCellera to develop an antibody treatment. That partnership began in February 2020, and by May the new drug,  bamlanivimab was already in clinical trials. Six months later, in November, the company received an emergency use authorization from  the FDA, and the Federal government contracted for 950,000 doses of the treatment at a price of $1.2 billion.  

Antibodies are naturally generated proteins that attack ‘invader’ proteins such as virus particles, which the body doesn’t recognize as its own. When exposed to a particular disease, everybody develops different antibodies, some of which are much more powerful than others. Biotech researchers take advantage of this by scouring thousands of antibodies generated in response to a particular disease in order to identify one that might work as therapies, which are commonly used against cancer and chronic diseases. For example, Abbvie had over $19.8 billion in 2020 sales on Humira, an antibody treatment for a type of inflammatory bowel disease and Merck’s sales of its Keytruda, its antibody therapy, reached $14.4 billion in 2020.  

But while antibodies for cancer and chronic disease can pay off for years, viral mutations can nullify a highly effective treatment for infectious disease. That was the case with Eli Lilly’s bamlanivimab. In clinical trials, the drug appeared to reduce viral load in Covid-19 patients within 11 days of treatment. But in March 2021,  its distribution as a therapy by itself was stopped by the U.S. government after it was found to be less effective against several circulating coronavirus variants that are monitored by the CDC, such as the B.1.427/B.1.429 variants that comprise over 50% of cases in California, though it remains effective against others like the B.1.1.7 variant that originated in the U.K. On Friday, the company asked the FDA to revoke the EUA for bamlanivimab as a solo treatment. 

As more variants of the SARS-CoV-2 virus are cropping up globally and making their way in the U.S., the pharmaceutical companies developing and manufacturing  antibodies against Covid-19 are reshaping their strategies to fight off the mutants.

“So even if one of our antibodies completely loses efficacy against the variants, with other antibodies at our disposal, that we can start scaling up very, very quickly,” says Christos Kyratsous, head of infectious disease R&D at Regeneron.

Antibodies are pivotal in fighting against the evolving virus, say health experts, even as vaccines continue to roll out, because there are populations who are likely to remain vulnerable to Covid-19. “There’s also a group of people who decline taking the vaccine and then there’s also another population whose immune systems may be compromised,” says Dr Sean Liu, medical director of Mount Sinai’s Covid Clinical Trials Unit. “Even if they get vaccinated, their vaccine may not be as effective for them.”

To keep ahead of the variants, earlier this month, the NIH updated its antibody treatment guidelines. The new recommendations call for a “cocktail-based approach” meaning that more than one anti-Covid antibody should be administered to patients. For example, the NIH recommends using bamlanivimab with another drug produced by Lilly called etesevimab, after a study showed this combination produced an 87% reduction in risks of hospitalization and death for Covid patients. Eli Lilly received an EUA for this antibody cocktail in February 2021.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Lilly’s Chief Science Officer Daniel Skovronsky said in a statement.’ 

Regeneron Pharmaceuticals was granted emergency use authorization for its cocktail of two antibodies, REGEN-COV, in November 2020. More recently, it asked the FDA for clearance to use this cocktail as a preventive treatment for Covid-19, since new data showed that it reduced risk of infection among people exposed to the virus. That’s on top of the 70% reduction in deaths and hospitalizations it saw with 4,500 patients during clinical study.  

In the face of circulating variants, researchers at the company have already started scanning its bank of antibodies to counter new mutations. “So even if one of our antibodies completely loses efficacy against the variants, with other antibodies at our disposal, that we can start scaling up very, very quickly,” says Christos Kyratsous, head of infectious disease R&D at Regeneron.

So far, Regeneron’s laboratory studies have shown that one of their antibodies was partially ineffective against the South African variant B.1.351, says Kyratsous, but both the antibodies together suppress the virus, he adds. “We are retaining full efficacy, against all the variants of concern.” However, there is still no data on the potency of the antibodies in vivo or in patient bodies, says Kyratsous.

Other companies working to develop Covid antibody treatments are working on ways to reduce the risks of mutation. For example, GlaxoSmithKline has partnered with the San Francisco-based startup Vir Biotechnology to develop its ‘dual action’ monoclonal antibody VIR-7831, for which the companies submitted an application for an EUA  last month. Vir’s antibody was isolated from the blood of a survivor of the SARS outbreak in 2002. The coronavirus that caused SARS is closely related to the one that causes Covid-19, and this antibody targets a site common to both viruses. This site doesn’t mutate nearly as easily as the parts of the coronavirus that have led to new variants, says Amanda Peppercorn, vice president clinical trials at GSK, which means it should theoretically be more able to handle new versions of the coronavirus.

Clinical trials of VIR-7831 showed an 85% reduction in hospitalization among 580 patients with Covid-19, says Peppercorn. However, the study had enrolled patients from August, 2020 to February 2021, when the currently circulating variants were not as prevalent. “At this point we don’t have sequencing data on the vast majority of our patients to know what our rates would look like in terms of variants of concern,” Peppercorn says. In lab studies, however, their antibody was found to be effective against variants of concern. “None of the variants have mutations in our binding site.”

Nevertheless, GSK is making preparations in case more variants show up and become resistant to VIR-7831. The company is working  with Eli Lilly to test it in combination  with Lilly’s bamlanivimab. “In a situation where we start to see resistance, for the long term we wanted the optionality for countries to be able to use VIR alone or in combination,” Peppercorn adds.

Yasmeen Long, a director at the Milken Institute’s FasterCures, which tracks Covid-19 vaccines and treatments, is optimistic. “Less than a year ago we were tracking less than 30 treatments,” says Long. Now there are 326 treatments currently in development. “I think things are looking positive on the horizon for us to mitigate this pandemic,” she says.

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