In this latest MedCram video, Dr. Seheult discusses a promising new drug that is being added to the arsenal of treatments against COVID-19. It is a new monoclonal antibody called vilobelimab.
What does vilobelimab do?
This drug has been given emergency use authorization not only for COVID-19 but it may also be applied to other scenarios. This new medication is a monoclonal antibody drug but uses a completely different mechanism than previous monoclonal antibodies that were used during the COVID-19 pandemic. It does not involve the spike protein. This antibody is directed against proteins that are endogenous to the human body and not anything on a specific virus.
Ways to improve the immune system
MedCram has discussed multiple other modalities to improve your immune system such as sunlight, near infrared light, hydrotherapy, vitamin d, nutrition, oxidative stress, and fresh air.
What is ARDS?
ARDS (acute respiratory distress syndrome) is the final common pathway for many viral illnesses, not only SARS-CoV-2. ARDS can lead to fibrosis in the lungs which affects the ability for oxygen to diffuse across the tissues and the ability of the lung to stretch with breathing. This can cause permanent disability. The fibrosis is caused by a person’s own immune system due to it getting ramped up too much.
How does the complement cascade work in ARDS?
The innate immune system is a portion of the immune system that deals with antigens but in a way that is not dependent on a particular type of antigen. It is dependent on proteins within a protein complex known as the complement cascade. Within this cascade you come to a protein called C5b and C5a. C5b goes on to combine with C6,C7,C8, and C9 to form a cylindrical complex membrane that can attack cells. This type of attack is very important in cases of meningitis. C5a goes on to become an anaphylatoxin which attracts other cells to the site of infection and causes damage to the surrounding area. It is often found in ARDS. If you can decrease the C5a response you can potentially reduce the inflammatory response that comes as a result of it.
How does the new monoclonal antibody work?
There are a few drugs that are available to try and block potential points of the complement cascade. Eculizumab, a different monoclonal antibody, is an antibody against C5 which is normally cleaved into C5a and C5b. The downside of this is the decreased levels of C5b which can interfere with the body’s ability to create the cylindrical membrane attack complex which essentially helps with killing unwanted cells or viruses in the body. Patients who receive eculizumab must be vaccinated against meningitis. Vilobelimab, the new drug, focuses only on the arm that decreases C5a. It is essentially a monoclonal antibody against C5a so it doesn’t interfere with C5b and its actions. Eculizumab in a study did not prevent or reduce C5a generation as there is another enzyme, trypsin, which can also cleave it from C5. This is important to realize since eculizumab doesn’t decrease C5a, then it most likely won’t reduce the inflammatory changes that are associated with it.
What did the vilobelimab trial show?
The phase 3 trial done with vilobelimab was a multicenter double-blinded randomized control trial. The total patients was 368 with 177 patients in the intervention arm and 191 in the placebo arm. It was done across 46 hospitals in Europe, North America, South America and Africa. The patients had to be 18+, on mechanical ventilation for less than 48 hours with moderate to severe ARDS. The intervention was standard of care plus vilobelimab 800 mg IV on days 1,2,4,8,15 and 22. The endpoint was all-cause mortality at 28 days. The study was originally done apriori with no site stratification. However, the FDA wanted site stratification which meant they did not want to include any information from the smaller sites if there were no deaths at those sites. Due to this, 61 people were eliminated from the study and the number went from 368 to 307. This would reduce the power of the study. So when the study was stratified by site it didn’t make statistical significance. However, if the original version of the study protocol was used without site stratification, then there was a significant reduction in all-cause mortality and there was statistical significance. It was because of this that the FDA allowed them to get EUA. The study did not show any statistical significance towards kidney injury; however, it was noted that vilobelimab seemed to protect against dialysis. On the subgroup analysis it appears that patient’s with more severe disease and lower GFR<60 did meet statistical significance as compared to those with moderate disease and GFR>60.
For safety, these patients are very sick patients and anything can happen. Once the drug is infused anything that happens afterward is attributed to the drug so the adverse events were high in both the infusion group as well as the placebo group at 91%. There was no major difference between the most common adverse events other than there was an increased incidence of pneumonia in the intervention group; however, this can be accounted for by the fact that there was a statistical decrease in mortality with vilobeimab and that patients that were still alive could develop pneumonia as dead people don’t have pneumonia. There were no cases of bacterial meningitis seen.
What is the potential of vilobelimab?
Currently we are not seeing a lot of hospitalizations in the U.S. from COVID-19;however, in the instance that a patient comes in to the hospital and ends up on the ventilator within 48 hours, this is a new “tool” in the “tool shed” that can be used for treatment. One positive aspect of this drug is that it is a monoclonal antibody where you don’t have to worry about the spike protein or sub variants that may arise in the future because it is not against the spike protein but instead is against C5a which causes inflammation. So the question is could this medication also work against other viral pandemics? There was a study published in 2015 that looked at H7N9 viral infection that looked at African green monkeys. They looked at the vilobeimab in treatment of this and they found that there appeared to be improved outcomes in the monkeys treated with the drug.
Vilobelimab factsheet
Today there are still people being admitted with severe COVID and this drug currently under emergency use authorization. Here is the factsheet for those that may need it for the drug. As always, more research is needed. If you are taking care of COVID 19 patients on the ventilator, MedCram has a free course on mechanical ventilation.
LINKS / REFERENCES:
Controlling the anaphylatoxin C5a in diseases requires a specifically targeted inhibition (Clinical Immunology) | https://www.sciencedirect.com/science…
The anti-C5a antibody vilobelimab efficiently inhibits C5a in patients with severe COVID-19 (Clinical and translational science) | https://pubmed.ncbi.nlm.nih.gov/35029…
Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial (Lancet Respir Med) | https://www.ncbi.nlm.nih.gov/pmc/arti…
Treatment With Anti-C5a Antibody Improves the Outcome of H7N9 Virus Infection in African Green Monkeys (Clinical infectious diseases) | https://www.ncbi.nlm.nih.gov/pmc/arti…
FACT SHEET FOR HEALTHCARE PROVIDERS: EMERGENCY USE AUTHORIZATION FOR GOHIBIC (FDA) | https://www.fda.gov/media/166824/down…
COVID-19 Ventilator Course: Learn or Review Mechanical Ventilation (MedCram) | https://www.medcram.com/courses/COVID…
All coronavirus updates are at MedCram.com (including more discussion on delta variant covid, COVID Delta, COVID children, natural immunity COVID 19, and more).
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