When vaccines fall short in offering relevant immune protection in the Immunocompromised, what really works? When such suboptimal immune protection wanes a lot faster in comparison to that immunocompetent individuals, is there a better option?
“Ready-made”, sustainable Immune Protection perhaps?
Well that’s exactly what Evusheld ® – drugmaker AstraZeneca’s “New Kid on the Block” in the long-acting monoclonal antibody drug combo can potentially offer.
The USFDA granted Evusheld ®, Emergency Use Authorization (EUA) on December 8th, 2021. The Authorization is based on findings from the PROVENT clinical trial. This is the first ever preventive, long-acting monoclonal antibody drug for “pre-exposure” prophylaxis in the arsenal to counter the COVID19 menace. These “readymade” antibodies will potentially prove beneficial for individuals with a weak immune system who are unlikely to mount an optimum and sustained immune response to the existing COVID19 vaccines. Patients with advanced CKD, those on Dialysis & Kidney Transplant recipients on anti-rejection medicines form a prominent cohort among those with immunocompromise. So, it is worthwhile for the kidney patient community to get the right facts about this option.
(Conflicts of interest: None)
WHAT IS EVUSHELD ®?
Evusheld ® is a long-acting antibody (LAAB) combination drug made of two monoclonal antibodies — Tixagevimab & Cilgavimab. These antibodies are a result of initial sourcing & development of B-cells from patients recovering from SARS-CoV-2 virus by researchers at Vanderbilt University Medical Centre (VUMC). Further, the antibodies were chemically modified by in-house technology at AstraZeneca to extend their circulation time in an individual’s bloodstream. This is the first such pharmacological immune protection option offering optimum “passive immunization” against COVID19.
Evusheld ® continues to be studied under the PROVENT Trial as a candidate for pre-exposure prophylaxis in unvaccinated immunocompromised. The study due to be completed in June 2022 recruited over 5000 volunteers with immunocompromise owing to different conditions including, but not limited to CKD & Solid Organ Transplant recipients.
Unlike the short-acting antibody cocktails in-use to treat COVID-19 infection, Evusheld ® shots are for uninfected individuals (like vaccines). It aims to provide “ready-made” immune protection in those with immunocompromise where vaccines are unlikely to help. As per PROVENT trial data, this drug offers robust, stable and still continuing immune protection at 6 months. Looking at how bodies process the drug, this protection will potentially remain for upto 12 months. As per Phase III trial data, Evusheld ® slashes the risk of contracting symptomatic COVID19 by an encouraging 83% in the immunocompromised volunteers who were given the drug as compared to Placebo (those not given the drug).
WHO IS ELIGIBLE TO RECEIVE EVUSHELD ®?
As per US FDA, Evusheld ® does not replace COVID19 vaccines in immunocompetent people who respond well to vaccines.
This drug combo is specifically for:
• Individuals with moderate to severe immunocompromise where COVID vaccines are unlikely to provide optimum immune protection. Eg: Organ Transplant recipients.
• Individuals with H/o allergy to COVID vaccines who couldn’t complete their primary series dose schedules and have remained unprotected.
HOW DOES EVUSHELD ® WORK?
Vaccines provide immune protection by coaxing a person’s healthy immune system to generate an antibody response against the specific microbe. In people with immunocompromise, this mechanism falls short. So “readymade” antibodies in Evusheld ® help by offering sustained immune protection without having to depend on the person’s immune system to respond.
Like most COVID vaccines in use, these antibodies target the COVID19 Spike Protein too. So, like vaccines, effectiveness of Evusheld ® against Omicron variant is under assessment as well. Will update in due course.
POTENTIAL PROS & CONS
1. Stable, adequate antibody protection from COVID19 for immunocompromised patients who may not derive optimum protection from vaccines (Pharmacological need of the hour!)
2. The documentation by AstraZeneca states that Evusheld ® shows “reduced Fc receptor binding“. Fc receptor binding is associated with the pathology of kidney diseases like IgA Nephropathy. This could mean that Evusheld ® may have significantly less chances of causing a flare up IgA Nephropathy when compared to IgAN flare-ups post COVID19 vaccines currently in use. However, pharmacovigilance studies will be crucial in concluding on this topic.
3. If suitably updated for added Omicron effectiveness, it is theoretically a better self-protection option in immunocompromised than repeated immune challenge with Vaccine Boosters
1. Expensive, check with your insurance if it plans to extend their coverage for the related cost
2. Cardiac adverse events (heart-related side-effects) were reported by a small number of trial volunteers with prior history of heart ailments. (No information on kidney related side effects yet)
TAKE HOME MESSAGE:
All things said and done, please note one thing.
The primary goal of preventive pharmacological tools against COVID19 namely Vaccines and Long Acting (monoclonal) Antibodies like Evusheld ® is to ensure self-protection from severe disease and death from the virus. Just like vaccines, these LAABs may not completely prevent viral transmission. Also, like vaccines, LAABs are in need of regular “upgrades”. This is to enable them to be effective against all circulating COVID19 mutant strains of concern, as and when these surface. This is similar to how annual flu shots get an upgrade every year to cover for new flu virus strains.
Therefore, even if you:
- Have received your vaccine primary dose(s)
- Got an extra primary or a booster dose
- Received Evusheld shot as a volunteer in its clinical trial
- Are unvaccinated due to a pre-existing medical condition like IgA Nephropathy that is likely to flare-up post vaccination
- Are unvaccinated due to allergy to any of the vaccine ingredient(s)
choose to stick to wearing a proper face mask covering your nose and mouth in public. This is to effectively block any potential exposure to the virus and diminish viral transmission among your contacts. Goes without saying, a strict hygiene protocol and avoiding crowds (indoors and outdoors) are a must add.
Unless all the above measures are rigorously adopted for at least another year, complete protection from the COVID19 will remain elusive.
Presenting a comparative analysis between COVID19 vaccines, Evusheld ® and Mask + Hygiene protocols in case of kidney patients with moderate to severe immuno-compromise here.
Stay sensible, logical, vigilant, responsible and safe all of you! 🙂
Deep gratitude for your continued interest in All Things Kidney Official.