Covid-19 drugmakers are hunting for new antibodies after warnings that some treatments may prove ineffective against rapidly spreading variants of the coronavirus.
Antibody treatments — such as the one given to Donald Trump when he contracted the virus in October — are used to bolster the immune systems of patients struggling to mount their own response. Trial data suggest the drugs, also known as monoclonal or “designer” antibody treatment, could also be used as a preventive measure in high-risk settings such as nursing homes.
But new studies show their effectiveness may be “severely” diminished by mutated strains of the virus, warned Anthony Fauci, chief medical adviser to the White House, this week.
A paper from scientists at Columbia University, yet to be peer-reviewed, said US drugmaker Eli Lilly’s treatment had failed to neutralise the 501.V2 coronavirus variant that first emerged in South Africa. The drug is one of two antibody treatments with US emergency approval and government contracts for hundreds of thousands of doses.
Unlike vaccines, some of which could be reformulated in weeks, companies producing such treatments would have to start the process from scratch if new variants evade their chosen antibodies, which can take months to grow. They would also have to win new authorisations from regulators.
Eli Lilly has already selected a potential 501. V2 treatment and said this week it was preparing to enter clinical trials in humans.
The company believes its development may be faster than the six months it took to create the original Covid-19 treatments. But it warned that it could still take that long to scale up to significant production levels.
“That's why we need to start working on variants as quickly as possible so that manufacturing can be scaled,” said Dan Skovronsky, chief scientific officer.
Antibody therapy is one of the fastest-growing fields of biomedical research and is used widely in the treatment of cancer and autoimmune diseases such as rheumatoid arthritis and Crohn’s.
It has been a scientific success in a process that has turned up few good drugs for Covid-19. However, treatments can be costly and tricky to administer, as they are an infusion, not a pill.
The median price in the US for a year’s antibody treatment for diseases such as cancer ranges from $15,000 to $200,000, according to the Wellcome Trust, a British research charity. As a result, 80 per cent of such therapies are sold in the US, Europe and Canada.
In the US, the government contracts mean the drugs are for now free of charge, although patients may face bills for the hospitals administering them.
The Columbia paper found the combination of two monoclonal antibodies from Regeneron, which also has a US emergency use authorisation, is active against the 501. V2 variant, even though one of the antibodies’ potency was reduced.
If it does need to adapt in the future, Regeneron said it already had a number of antibodies waiting in the wings that were not used in the final cocktail.
Eli Lilly is working with the UK’s GlaxoSmithKline and San Francisco-based Vir Biotechnology in an unusual collaboration to launch a trial of a cocktail of all of their antibodies.
George Scangos, Vir chief executive, said “every company that makes antibodies anticipated that escape mutations would happen”, and warned that the virus may now start mutating at a more rapid rate.
“This is the tip of the iceberg, these are the first ones,” he said. “As more people get vaccinated and recover then the virus comes under selective pressure.”
Dr Scangos said his team was testing hundreds of different antibodies to identify ones that work against the new variants.
Seattle-based Adaptive Biotechnologies, which is also developing antibody treatments, is in discussions with regulators about what would be needed to bring forward promising therapies without having to undergo the same onerous studies.
“Once you’ve built up that manufacturing capacity you’re committed to that, and it’s very hard to pivot without having a big impact on delivery,” said Lance Baldo, chief medical officer at Adaptive.
The UK regulator has not yet approved any antibody treatments for emergency use but the government has an in-principle agreement to secure access to 1m doses of an antibody cocktail being produced by AstraZeneca, pending trial results.
In the US, Dr Fauci said he planned to work with companies to develop alternatives or boosters for antibody treatments that would use the same platforms rather than replace products completely.
“We will always want to be a step or two ahead of what might be a problem in the future,” he said.