Monoclonal antibodies may be a COVID-19 game changer. But will they be accessible to everyone ?
Collaboration is key to developing an antibody cocktail that is affordable and available in all countries in need.
Julien Potet, MSF Access Campaign Policy Advisor, NTDs and Vaccines
At a time when, every day, we read about new developments in the race to develop a new vaccine against COVID-19, there’s another very significant race against the virus under way that has not been adequately put in the media spotlight.
Anti-SARS-CoV-2 monoclonal antibodies, hereafter referred to as anti-SARS2 mAbs, are possible game changers to treat or even prevent COVID-19. And there’s currently a great deal of activity and excitement in the race to develop them — fast.
So what are these antibodies and how do they work?
Following infection with a virus, people produce an antibody response. Many different sorts of antibodies that bind to the virus in different locations are naturally produced by their immune system. Some of them are capable of ‘neutralising’ the virus and preventing the damage it does. Anti-SARS2 mAbs are synthetic ‘clones’ of these same, naturally occurring, neutralising antibodies.
There are two predominant ways to acquire these antibodies for research; a few research teams have managed to derive anti-SARS2 mAbs from animals immunised with a COVID-19 vaccine candidate, but most anti-SARS2 mAbs in the pipeline stem from convalescent COVID-19 patients who consented to donate samples of their blood for follow-on research.
Right now multiple research teams are focused on developing anti-SARS2 mAbs. Each team often has several antibodies in their portfolio. So that means there are at least 50 of these molecules currently working their way through the development pipeline, and probably many more.
Big pharma in pole position
Both the big pharmaceutical companies like Regeneron, Lilly, GSK and Amgen, and small biotechs and academic teams, are working as fast as they can to bring winning candidates through the pipeline to regulatory approval. Because of their capacity to mobilise resources quickly, the big companies have naturally been able to move ahead much faster.
However, the anti-SARS2 mAbs supported by pharma are not necessarily the most potent and effective against the virus. And this could be a problem if they end up being the first to market: a less potent mAb will require a very high dose to show clinical benefit. And this will have large cost implications.
For instance, we know it costs no less than US$50 to manufacture 1g of synthetic mAb for clinical use in large bioreactors. Imagine then that the required dosage for mAb ‘X’ in an adult is 0.5g and for mAb ‘Y’, also for an adult, is 5g because of their different potencies. The cost to manufacture a treatment course of mAb ‘X’ could be as low as $25 while it would be at least $250 for mAb ‘Y’. That’s a very significant difference. In addition, treatment courses of mAb ‘X’ could be produced much more rapidly because of the requirement for lower dosage. That’s why it is important to identify the most potent mAbs across the field at this early stage in order to prioritise their development and accelerate their availability for people.
This is precisely the objective of the Coronavirus Immunotherapy Consortium, CoVIC, established with the support of the Bill and Melinda Gates Foundation’s Therapeutics Accelerator and other stakeholders. It aims for an objective, blinded head-to-head comparison of all the pipeline mAbs, both in terms of their capacity to neutralise SARS-CoV-2, and also importantly in terms of ease of manufacture on a large scale. At the end of the day, these experiments will allow for the identification of optimal lower-cost cocktails of a couple of mAbs — using combinations in order to reduce the risk of the virus becoming resistant. But for this initiative to be successful and accomplish its objective, it is important that all mAb manufacturers agree to share their mAbs with CoVIC.
Is this going to happen? Nothing is certain. Several large pharma companies are already advancing their mAbs outside this collaborative effort. Regeneron and Lilly, among others, have started clinical trials on their candidates. The encouraging news is that ACTIV — the private-public partnership supported by the National Institutes of Health — is now requiring that anyone who wants to have their mAbs included in ACTIV-sponsored clinical trials, must also submit their samples to CoVIC, as well as a US government lab.
How can we ensure supply meets demand?
But there’s a further obstacle to overcome. Can manufacturing capacity possibly meet global demand? Duke University has noted that the needs in the US alone are likely to be huge. It’s becoming clear that big companies with anti-SARS2 mAb candidates have already secured deals with contract manufacturers, and agreements among themselves, in order to be able to rapidly expand production capacity once the results are out and a winner is declared. While contract manufacturers, at least those in high-income countries, have been ‘reserved’ by large pharma companies, other groups developing anti-SARS2 mAb may have difficulties in finding manufacturing partners for mass production.
There is of course also the significant likelihood that the available doses will be hoarded by rich country governments, as we have seen already in the US government’s attempt to ‘grab’ potentially useful drugs such as Gilead’s remdesivir. Let it be noted that Regeneron has already signed a US$450 million procurement deal with the US strategic national stockpile.
And finally, there’s also a very high probability that for-profit pharma companies will hike the prices well beyond actual manufacturing costs and put these drugs out of reach of people and governments in developing countries. We’ve seen this happening already with many mAbs for other indications, particularly for cancer.
So how can we try to ensure equitable access to these lifesaving new medicines?
There are a few things to be done:
First, we need to fine-tune the estimated global needs by identifying the high-risk groups within populations that will most benefit from anti-SARS2 mAbs. This could then allow the limited quantity of anti-SARS2 mAbs produced annually to be distributed equitably across the different countries in need.
Second, the WHO Access to COVID-19 Tools (ACT) Accelerator initiative, whose objective is precisely to deliver affordable effective medical tools for resource-limited settings, should focus its efforts on the most potent anti-SARS2 mAb candidates supported by academic research teams. These teams are more likely than private for-profit companies to agree to sell their mAbs at cost.
Finally, while there is limited manufacturing capacity in high-income countries, efforts should be stepped up to tap into the new mAb manufacturers that have been established in middle-income countries over the last decade, particularly in Latin America, India and China. This will require some technical and financial support to manufacturers in the developing world. But it is worth it in the short term, in order to increase global supply capacity of anti-SARS2 mAbs, and in the longer term to improve access to mAbs for other diseases in resource-limited settings.
Whatever the final therapeutic game changer against COVID-19 turns out to be — an anti-SARS2 mAb cocktail, a small molecule antiviral, an immune modulator, or a combination of these — we will need to strive for equitable access. We know the answers won’t all lie in the boardrooms of the pharma industry. What’s needed now more than ever is for governments to step up and make good on their public pronouncements about solidarity and equity in managing the pandemic. In a time of COVID-19, it is only through a firm and global political commitment to mechanisms such as the WHO’s Equitable Allocation Framework that we can hope to ensure equitable access for everyone to the medical treatment they need.