Pemivibart only option against ‘false reassurance’ of reduced SARS-CoV-2 virulence
The next phase of pre-exposure prophylaxis against SARS-CoV-2 currently rests on the shoulders of a single monoclonal antibody product — but it may not be enough for immunocompromised populations.
Pemivibart (Pemgarda, Invivyd) was granted emergency use authorization by the FDA in March 2024 for injectable use every 3 months in adults and adolescents aged 12 years or older who weigh at least 40 kg. It targets the spiked protein of the virus and can be used in individuals who are not currently infected with SARS-CoV-2 or who have not had contact with the virus.
Despite this advance, Leonard Calabrese, DO, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, and chief medical editor of Healio Rheumatology, believes that it may not be enough for the “hundreds of thousands” of immunocompromised patients treated by rheumatologists and other associated specialists.
Healio sat down with Calabrese to discuss the current state of COVID-19 prevention, the dual approaches of vaccination and monoclonal antibody treatment, and considerations for the FDA moving forward.
Healio: Where do we stand with antivirals for COVID-19 at the moment?
Calabrese: First off, the whole area of monoclonals and COVID-19 has been marginalized and, unfortunately, put into the background of what is going on in health care. We have been without an effective monoclonal to treat this virus for the most vulnerable of our patients, including those on B-cell depleting agents and other forms of immunosuppression like cyclophosphamide. Across all indications, that is hundreds of thousands of people.
There is this sense that everything is fine because of the decreased intensity of COVID-19 in its present form in a general population of people with a lot of background immunity — but this is a false reassurance. It leaves a very vulnerable group out. This is a small part of our practice but a very important one.
Healio: Can vaccination and treatment with monoclonals work together to protect this vulnerable population?
Calabrese: Because of the shifting evolution of the virus, it has been one step ahead of monoclonals.
Unfortunately, the FDA the has been totally out of touch on addressing this issue. New vaccines are updated and put into the population without additional clinical trials based on ex vivo analysis of activity. The same should be done and must be done for monoclonals.
Healio: Could you talk about how pemivibart fits into this equation?
Calabrese: This company has taken a big step forward. They just published in the New England Journal of Medicine a highly reproducible and valuable ex vivo testing system that gives us a read on the activity of the existing antibodies against the evolving strains of COVID-19. These are viruses that have entered the population after the product has been developed. The results showed us good residual activity that indicate that it can and should be used against this evolving virus.
So, now a conversation needs to take place. We need a wake-up call for clinicians and practitioners to refocus on that small but highly vulnerable population. We need to get them on monoclonals. This product is an infusion once every 3 months and is generally well tolerated.
Healio: What is happening in the pharmaceutical landscape in terms of developing more such products?
Calabrese: Big companies that have been in the monoclonal space have dropped out, not necessarily because of purely financial reasons, but because of regulatory roadblocks. The FDA needs to pay greater attention to immunocompromised populations.
It raises the question of why they approve new vaccines based only on ex vivo data but do not do the same for monoclonals. This can’t happen.
Healio: Do you foresee hope with this NEJM article?
Calabrese: Possibly. This ex vivo analysis was somewhat of a breakthrough, so I am hopeful that people will start paying attention. It is possible that this type of analysis could be accepted widely by the FDA for future monoclonals. It is a good step in that direction.
Healio: Shifting gears, do you see an overall fatigue with COVID-19 as part of the regulatory and development malaise surrounding products to protect patients from the virus?
Calabrese: Clearly that is absolutely happening. We are very grateful that the brunt of this pandemic is behind us, but at the same time there are still populations that are being increasingly forgotten.
This population is still at risk for severe complications like hospitalization, intensive care and death. This also puts them at risk for advanced forms of long COVID. We are finding it difficult to keep an interest up in this virus.
Healio: Did you find there to be COVID-19 fatigue at ACR Convergence 2024?
Calabrese: I would not call it fatigue, but it has definitely been placed in the background of our priorities. It is really time to rekindle an active interest and be proactive and get this medication to the small but most vulnerable part of our practice.
Reference:
Schmidt P, et al. New Engl J Med. 2024;doi:10.1056/NEJMc2404555.
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