Monoclonal antibody treatment for COVID-19 patients

[Astronuc]

Eli Lilly says its monoclonal antibody prevented Covid-19 infections in clinical trial
https://www.statnews.com/2021/01/21...ntibody-prevented-covid-19-in-clinical-trial/

I heard that the infection was less severe and prevented some patients from requiring hospitalization. One would not receive monoclonal antibodies unless one had an infection. That's more in line with what The Hill has reported today.

Eli Lilly says antibody combo significantly cuts COVID-19 death risk
https://thehill.com/policy/healthca...ody-combo-significantly-cuts-covid-death-risk

A combination treatment of two monoclonal antibodies developed by Eli Lilly can significantly reduce hospitalizations and deaths due to COVID-19, the company announced Tuesday.

The results from a final-stage clinical trial of more than 1,000 patients testing the combination of bamlanivimab and etesevimab found just 11 hospitalizations in patients taking the therapy, compared to 36 events in patients taking a placebo, a 70 percent reduction compared to a placebo.

Back in December, NPR reported Low Demand For Antibody Drugs Against COVID-19
https://www.npr.org/sections/health...ow-demand-for-antibody-drugs-against-covid-19

Federal officials are disappointed to find that the monoclonal antibody drugs they've shipped across the country aren't being used rapidly.

These drugs are designed to prevent people recently diagnosed with COVID-19 from ending up in the hospital. But hospitals are finding it cumbersome to use these medicines, which must be given by IV infusion. And some patients and doctors are lukewarm about drugs that have an uncertain benefit.

So we've been losing between 3000 and 4000 people a day, and folks are reluctant to use an apparently effective treatment?

Back in November 2020, FDA Authorizes Monoclonal Antibody for Treatment of COVID-19
https://www.fda.gov/news-events/pre...orizes-monoclonal-antibody-treatment-covid-19

Today, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for the investigational monoclonal antibody therapy bamlanivimab for the treatment of mild-to-moderate COVID-19 in adult and pediatric patients. Bamlanivimab is authorized for patients with positive results of direct SARS-CoV-2 viral testing who are 12 years of age and older weighing at least 40 kilograms (about 88 pounds), and who are at high risk for progressing to severe COVID-19 and/or hospitalization. This includes those who are 65 years of age or older, or who have certain chronic medical conditions.

While the safety and effectiveness of this investigational therapy continues to be evaluated, bamlanivimab was shown in clinical trials to reduce COVID-19-related hospitalization or emergency room visits in patients at high risk for disease progression within 28 days after treatment when compared to placebo.

 

[Tom.G]

Yeah, sounds crazy on the surface.
Hear is another way of looking at it.
A) Assign some medical personnel, for a few hours, to monitor the antibody infusion to people that may not even need hospitalization.
B) Assign those medical personnel to care for those already hospitalized, some in ICU.

I'm not trying to say which may be better/worse, just that their seems an unstated assumption of unlimited available personnel/space. The word "Triage" comes to mind.

 

[BillTre]

I think there is a big difference between the people doing blood infusions, in a somewhat laid back clinical situation, and the highly trained people working in an ICU, where critical intense life sustaining care is standard.
These people are not that interchangeable.

 

[jim mcnamara]

Anybody who does phlebotomy (draw blood) or sets up infusions (like a drip into a vein) can set up and run this therapy. Apparently in New York they are seriously considering doing this at home for home-bound patients who test Covid positive and are in phase 1 (infected, asymptomatic)

Anyway, it is not that big a deal. But. Insurance companies are currently pushing back.
Source Daniel Griffin MD PhD: https://www.microbe.tv/twiv/twiv-710/ Circa 25 minutes

 

[Astronuc]

An experimental monoclonal antibody treatment for COVID-19 being developed by Eli Lilly and Co (LLY.N) and AbCellera Biologics Inc (ABCL.O) can "potently" neutralize numerous Coronavirus variants, including those first identified in the UK, Brazil, South Africa, California and New York, scientists have found in test tube experiments. The antibody - known as LY-CoV1404 or LY3853113 - works by attaching itself to a place on the virus that has shown few signs of mutating, which means the drug is likely to retain its effectiveness over time, the researchers said in a report posted on Friday on bioRxiv ahead of peer review. "New variant-resistant treatments such as LY-CoV1404 are desperately needed, given that some of the existing therapeutic antibodies are less effective or ineffective against certain variants and the impact of variants on vaccine efficacy is still poorly understood," the research team wrote.

https://www.reuters.com/business/he...nts-lab-study-covid-19-antibodies-2021-05-03/

 

[Ygggdrasil]

https://www.reuters.com/business/he...nts-lab-study-covid-19-antibodies-2021-05-03/

Here's a link to the non-peer reviewed pre-print manuscript discussed in the news article:

LY-CoV1404 potently neutralizes SARS-CoV-2 variants
Westendorf et al. bioRxiv 2021
https://www.biorxiv.org/content/10.1101/2021.04.30.442182v3

Abstract:

LY-CoV1404 is a highly potent, neutralizing, SARS-CoV-2 spike glycoprotein receptor binding domain (RBD)-specific antibody identified from a convalescent COVID-19 patient approximately 60 days after symptom onset. In pseudovirus studies, LY-CoV1404 retains potent neutralizing activity against numerous variants including B.1.1.7, B.1.351, B.1.427/B.1.429, P.1, and B.1.526 and binds to these variants in the presence of their underlying RBD mutations (which include K417N, L452R, E484K, and N501Y). LY-CoV1404 also neutralizes authentic SARS-CoV-2 in two different assays against multiple isolates. The RBD positions comprising the LY-CoV1404 epitope are highly conserved, with the exception of N439 and N501; notably the binding and neutralizing activity of LY-CoV1404 is unaffected by the most common mutations at these positions (N439K and N501Y). The breadth of variant binding, potent neutralizing activity and the relatively conserved epitope suggest that LY-CoV1404 is one in a panel of well-characterized, clinically developable antibodies that could be deployed rapidly to address current and emerging variants. New variant-resistant treatments such as LY-CoV1404 are desperately needed, given that some of the existing therapeutic antibodies are less effective or ineffective against certain variants and the impact of variants on vaccine efficacy is still poorly understood.​

​

In Brief LY-CoV1404 is a potent SARS-CoV-2-binding antibody that neutralizes all known variants of concern and whose epitope is rarely mutated.​

 

[Astronuc]

FDA authorizes REGEN-COV monoclonal antibody therapy for post-exposure prophylaxis (prevention) for COVID-19
https://www.fda.gov/drugs/drug-safe...post-exposure-prophylaxis-prevention-covid-19

The U.S. Food and Drug Administration today revised the emergency use authorization (EUA) for REGEN-COV (casirivimab and imdevimab, administered together) authorizing REGEN-COV for emergency use as post-exposure prophylaxis (prevention) for COVID-19 in adults and pediatric individuals (12 years of age and older weighing at least 40 kg) who are at high risk for progression to severe COVID-19, including hospitalization or death. REGEN-COV is not authorized for pre-exposure prophylaxis to prevent COVID-19 before being exposed to the SARS-CoV-2 virus -- only after exposure to the virus.

I found a link to this on the Florida Health Department Covid Response website. https://floridahealthcovid19.gov/

 

[Ygggdrasil]

Because each monoclonal antibody targets only one epitope on the virus, mAb treatments are going to be very susceptible to virus variants gaining resistance through mutation of those epitopes (in contrast, vaccination elicits a wide variety of antibodies and T-cells that can recognize a larger number of epitopes, making it harder for the virus to elude an immune response from a vaccinated individual). As new variants arise, it will be important to check that the mAbs still work to neutralize the new variants.

 

[Astronuc]

Some remote family members (cousins or second/third cousins somewhat removed) have been put on REGEN-COV monoclonal antibody therapy due to Covid-19. Infections were spread in a family gathering.

Edit/update: We haven't confirmed, but it our understanding that the family members in question were/are not vaccinated, nor do they necessarily wear masks or practice social distancing.

 

[Astronuc]

GlaxoSmithKline and Vir Biotechnology recently conducted a huge collaborative study by scientists and developed a new antibody therapy, called Sotrovimab. During the project, they discovered a new natural antibody “that has remarkable breadth and efficacy,” according to the Berkeley Lab.

The scientists reportedly discovered a new antibody, called S309, which “neutralizes all known SARS-CoV-2 strains — including newly emerged mutants that can now ‘escape’ from previous antibody therapies — as well as the closely related original SARS-CoV virus,” according to a press release from the Berkeley Lab.

Structural biologist Jay Nix, who was involved with the project, said the antibody can potentially stop all coronaviruses similar to COVID-19.

Deseret News - https://www.deseret.com/coronavirus...ps-covid-19-coronavirus-variants-delta-lambda

The data supporting this EUA for sotrovimab are based on an interim analysis from a phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in 583 non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. Of these patients, 291 received sotrovimab and 292 received a placebo within five days of onset of COVID-19 symptoms. The primary endpoint was progression of COVID-19 (defined as hospitalization for greater than 24 hours for acute management of any illness or death from any cause) through day 29. Hospitalization or death occurred in 21 (7%) patients who received placebo compared to 3 (1%) patients treated with sotrovimab, an 85% reduction.

https://www.fda.gov/news-events/pre...tional-monoclonal-antibody-treatment-covid-19

Of course, there are side-effects

The EUA allows for sotrovimab to be distributed and administered as a 500 milligram single dose intravenously by health care providers. The EUA requires that fact sheets that provide important information about using sotrovimab in treating COVID-19 be made available to health care providers and to patients, parents and caregivers, including dosing instructions, potential side effects and drug interactions. Potential side effects of sotrovimab include anaphylaxis and infusion-related reactions, rash and diarrhea.

https://www1.racgp.org.au/newsgp/clinical/what-is-the-covid-19-treatment-sotrovimab

 

[Astronuc]

A technology developed at Vanderbilt University Medical Center has led to the discovery of an "ultra-potent" monoclonal antibody against multiple variants of SARS-CoV-2, the virus responsible for COVID-19, including the delta variant.

https://phys.org/news/2021-09-ultra-potent-antibody-covid-variants.html

The technology, called LIBRA-seq, has helped speed up the discovery of antibodies that can neutralize SARS-CoV-2. It also enables researchers to screen antibodies against other viruses that have not yet caused human disease but which have a high potential of doing so.

 

[Astronuc]

Doctors are often unaware of the only treatment for early Covid-19​

https://www.cnn.com/2021/10/25/health/covid-antibody-treatment-doctors/index.html

Many patients who qualify for the drugs say their doctors never mentioned them, even though it has been nearly a year since antibodies were first authorized by the US Food and Drug Administration, they're the only treatment for early Covid, and studies have shown they can dramatically reduce the risk of hospitalization and death.

If patients do manage to learn about antibodies, they can then face another challenge. As Covid-19 numbers surged this summer and early fall, some hospitals, and even community groups, rose to the occasion and started helping large numbers of patients gain access to the drugs. But some major, well-resourced medical centers say staffing and space shortages have prevented them from offering more than just a handful of treatments per day.

"Some [hospitals] simply are not in a position to reallocate resources for providing monoclonal antibody treatments," said Akin Demehin, the American Hospital Association's director of policy.

The end result is that many Covid-19 patients are left hunting on their own for the only drug that can help them.

Kidda's cousin, a nurse, then told her about the treatment, so Kidda called a government hotline for monoclonal antibodies and was given names and numbers for 10 treatment sites near her father's home.

"Eight of them were like, 'why are you calling us?' " she remembers.

The ninth treatment center said her father would need a referral from his doctor. Kidda called her father's doctor, but she said he wouldn't give a referral, and wouldn't explain why.

The tenth center said it would take the first 50 people who showed up in the morning. Daniell arrived 15 minutes after the center opened and there were already more than 50 people in line.

 

[Laroxe]

I don't think these drugs were ever going to take off in a major way, there are just too many issues that complicate their use & it's not surprising that the insurance companies are concerned, they are expensive. There is an issue about the state funding these drugs if people refuse vaccination, the drugs themselves are around 100 times more expensive and require a costly infrastructure. In the USA it seems unlikely that the costs of the medical prevention/management will continue to be paid for by the state, particularly when vaccine refusal is so common.
The idea was that they would be used in people already identified as at high risk of developing serious disease, and they only have a significant benefit if given early. If they are given following exposure, then we might be exposing people to drug side effects that might never develop covid. If we wait until the person becomes symptomatic we are left with a very limited window of opportunity for the effective use of these drugs. This again would be based on predicting the disease will run a serious course, the majority would not. The increased demand for these drugs appears to be based on their use in people already hospitalised and seriously ill, at this point the drugs are far less effective.
The fact that the drug is given IV means the development of an infrastructure to respond quickly, ideally the drug would be best used away from hospital settings, these carry their own risks. So teams that can go out to patients homes and administer the drug would be the best, the crystal balls would be out again trying to predict the likely need in the community.
The arrival of the new antiviral drugs like Molnupiravir, developed with government funding, which Merck is selling for 40 times its production cost, that can be given orally is still cheaper and will likely see the use of monoclonals disappear. The increased funding for drug development means that it is likely other drugs will soon follow, the research program has also lead to the identification of a range of drugs already available that modify the outcome of Covid-19 these include fluvoxamine and possibly statins.