There are many excellent sites which are systematically tracking the progress of all vaccines and treatments in development across the world. For those with interest, here are several that we recommend:
We are focused here on antibody-based the treatments that that are:
- in advanced stage of development and trials;
- have shown strong efficacy and safety thus far;
- are available in North America now – or will be soon – and have substantial funding and production capacity to ramp up supply; and
- are suitable to the prevention and prophylaxis uses cases (i.e. preventing infection or severe disease prior to hospitalization) in addition to treatment of patients with mild to moderate symptoms.
Antibody-based Therapeutics Have Now Arrived
When we started, this strangely seemed to be a well kept secret, but over the course of Q4, 2020 that changed. A likely reason why President Trump and former Governor Christie are both walking around today and not in the ICU or worse is that they received early testing and rapid treatment with Regeneron’s monoclonal antibody cocktail! On December 3, 2020, the NIH also added Casirivimab Plus Imdevimab Combination (Regeneron) and Bamlanivimab to its guidelines for treatment of COVID-19, emphasizing the need for early use (and that they are not considered to be effective after hospitalization for severe disease).
- NIH COVID-19 Treatment Guidelines: Therapeutic Management of Patients with COVID-19
- How Antibodies Help Your Body Beat COVID-19
But Distribution and Supply Are Big Problems
There are still two key problems – which this site is dedicated to address – that are not getting sufficient attention.
1. Building awareness and avenues to connect people in vulnerable population groups that have been infected to rapid treatment with antibody-based drugs.
- The avenues of distribution for these medicines are currently through the states – which is published on this HHS site.
- While some states have well organized systems in place, many other states have been more chaotic, and public attitudes have been politicized.
- This is something that can start saving lives the very short term, if states are proactive in taking advantage of it.
2. Ramping up production to address the prevention use case – not just treatment – for vulnerable groups.
- While the vaccine data is very encouraging, long experience with the Flu and Coronavirus family, as well as respiratory viruses generally indicate significant risk that vaccines will not be optimally effective for population groups that are most vulnerable to severe outcomes from COVID-19.
- Therefore it is critical that we continue to ramp production and distribution, and drive awareness to leverage antibodies to protect these groups even after vaccine distribution commences.
- This is something that would help to save many more lives while distribution of the vaccine ramps up.
The Federal Government, State governments and public health community are working hard to establish protocols and processes for distribution of these therapies, and rapid but equitable application to those most likely to benefit. Distribution of antibody therapies is being documented and published by the US Department of Health and Human Services on this site:
- HHS.gov: Monoclonal Antibodies for High Risk COVID-19 Positive Patients
- Bamlanivimab (Eli Lilly) Allocation by Jurisdiction
- Casirivimab/Imdevimab (Regeneron) Allocation by Jurisdiction
- Operation Warp Speed: OWS Therapeutics: Monoclonal Antibody Playbook
Eli Lilly’s Phase 3 Trial of LY-CoV555 for Prevention of COVID-19 at Long-Term Care Facilities in Partnership with the National Institute of Allergy and Infectious Diseases (NIAID) in July demonstrated over 74% reduction in hospitalizations with early treatment. Lilly received major funding from Operation Warp Speed to both accelerate their path to market and ramp up production, and have a manufacturing partnership with Amgen to support this. It received Emergency Use Authorization from the FDA on November 9, 2020.
|Description||LY-CoV555, with the brand name Bamlanivimab is a potent, neutralizing IgG1 monoclonal antibody (mAb) directed against the spike protein of SARS-CoV-2. It is designed to block viral attachment and entry into human cells, thus neutralizing the virus, potentially preventing and treating COVID-19. LY-CoV555 emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19 . LY-CoV016 (also known as JS016) is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can effectively block the binding of the virus to the ACE2 host cell surface receptor. Point mutations were introduced into the native human IgG1 antibody to mitigate effector function.|
|How Administered||Liquid solution with intravenous administration via medical staff.|
|Stage||Phase 3 Trials completed, Emergency Use Authorization approved on November 9th, 2020. Nationwide distribution has commenced, and weekly allocations and distribution to each state can be viewed on this HHS Web site. There is also ongoing expanded ACTIV-2 trial called Rise Above COVID to further test and demonstrate efficacy of various use cases, including prevention of infection as well as treatment after infection. Preliminary results of a Phase 3 BLAZE-2 COVID-19 prevention trial conducted in partnership with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), and the COVID-19 Prevention Network (CoVPN) – demonstrated an 80% reduction in infection and disease among nursing home residents with recent confirmed exposures to COVID-19.|
|Efficacy||Phase 1/2/3 Trials completed in July demonstrated over 74% reduction in hospitalizations with early treatment. Data from a new interim analysis of the BLAZE-1 clinical trial showed that combination therapy with two of Lilly’s SARS-CoV-2 neutralizing antibodies reduced viral load, symptoms and COVID-related hospitalization and ER visits. The randomized, double-blind, placebo-controlled Phase 2 study evaluated LY-CoV555 and LY-CoV016, which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in the outpatient setting.|
|Safety||The ACTIV-3 Trial, which was focused on hospitalized patients with severe COVID-19, was paused on October 17th for safety review and then stopped on October 26th. This was due to the finding that the treatment was not effective at this late stage of the disease, which was suspected given our understanding of how antibodies work. The other trials for the use of Bamlanivimab for early treatment and prevention continued and were successfully completed, with no significant safety concerns or side effects detected. This resulted in Lilly’s Emergency Use Authorization application and subsequent approval.|
|Current Production and Availablity||Lilly announced on October 28, 2020 an initial agreement with the U.S. government to manufacture 1,000,000 vials of bamlanivimab during 2020, with 300,000 vials within 2 months after EUA, for the treatment of mild to moderate COVID-19 in high-risk patients for $375 million – with acceptance pending grant an Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA). The initial agreement was for delivery over the two months following an EUA and also provided the option for the U.S. government to purchase up to an additional 650,000 vials through June 30, 2021 under the same terms as the base agreement and subject to agreement from Lilly, product availability and the medical need in the U.S.
Distribution of Bamlanivimab is documented and published by the US Department of Health and Human Services on this page: Allocation of Bamlanivimab by Jurisdiction.
|Production Capacity||Lilly has formed a manufacturing partnership with Amgen and can ramp up to produce up to 1,000,000 doses per month in Q1 2021.|
|Links||Fact Sheet on Bamlanivimab
Lilly Bamlanivimab Antibody Playbook
Rise Above COVID: ACTIV2 Trial Enrollment
January 21, 2021: Lilly’s neutralizing antibody bamlanivimab (LY-CoV555) prevented COVID-19 at nursing homes in the BLAZE-2 trial, reducing risk by up to 80 percent for residents
November 9, 2020: FDA Approves Eli Lilly’s Monoclonal Antibody Cocktail
Oct. 28, 2020: Lilly announces agreement with U.S. government to supply 300,000 vials of investigational neutralizing antibody bamlanivimab (LY-CoV555) in an effort to fight COVID-19
Oct. 28, 2020: NEJM – SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19
Oct. 7, 2020: Lilly provides comprehensive update on progress of SARS-CoV-2 neutralizing antibody programs
ClinicalTrials.gov: A Study of LY3819253 (LY-CoV555) and LY3832479 (LY-CoV016) in Participants With Mild to Moderate COVID-19 Illness (BLAZE-1)
Fact Sheet – Lilly’s Quest for COVID-19 Treatments: Neutralizing Antibodies
Regeneron’s Phase 3 trial of REGN-COV2 demonstrated strong efficacy for its ability to prevent coronavirus infection among uninfected people who have had close contact with an infected person, such as a patient’s housemate. It received a great deal of publicity when used to treat President Trump and former Governor Chris Christie. It received Emergency Use Authorization from the FDA on November 21, 2020.
|Description||REGEN-COV2, released under the brand name Casirivimab/Imdevimab, is a combination of two monoclonal antibodies (REGN10933 and REGN10987) and was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19. To develop REGN-COV2, Regeneron scientists evaluated thousands of fully-human antibodies produced by the company’s VelocImmune® mice, which have been genetically modified to have a human immune system, as well as antibodies identified from humans who have recovered from COVID-19. The two potent, virus-neutralizing antibodies that form REGN-COV2 bind non-competitively to the critical receptor binding domain of the virus’s spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen in the human population, as detailed in Science. Preclinical studies have shown that REGN-COV2 reduced the amount of virus and associated damage in the lungs of non-human primates.|
|How Administered||Liquid solution with intravenous administration via medical staff.|
|Stage||Phase 3 Trials completed, Emergency Use Authorization (EUA) application approved.|
|Efficacy||Reduced viral load and the time to alleviate symptoms in non-hospitalized patients with COVID-19. REGN-COV2 also showed positive trends in reducing medical visits. Viral loads were reduced between 50% to 99% versus placebo in clinical trials. The higher the viral load – the worse the infection – the better it worked.|
|Safety||Regeneron’s application for EUA was based on the good safety profile demonstrated in Phase 1/2/3 trials to date. More than 2,000 people have been enrolled across the overall REGN-COV2 development program, and no unexpected safety findings have been reported by the Independent Data Monitoring Committee. Both doses were well-tolerated. Infusion reactions were seen in 4 patients (2 on placebo and 2 on REGN-COV2). Serious adverse events occurred in 2 placebo patients, 1 low dose patient and no high dose patients. There were no deaths in the trial.|
|Current Production and Availability||The U.S. Department of Health and Human Services (HHS) and Department of Defense (DoD) announced on July 27, 2020 an agreement with Regeneronto demonstrate commercial-scale manufacturing of REGN-COV2, to produce between 70,000 and 300,000 treatment doses for $450 million. The federal government has committed to making the doses that have already been produced available to the American people at no cost and is responsible for their distribution. As of November 21, there were doses available for approximately 50,000 patients, and Regeneron expected to have doses available for 300,000 patients in total by the end of 2020.
Distribution of Bamlanivimab is documented and published by the US Department of Health and Human Services on this page: Casirivimab/Imdevimab (REGEN-COVE2) Allocation & Distribution Process
|Production Capacity||Regeneron has recently partnered with Roche to increase the global supply of REGN-COV2. Under this agreement, overall capacity of REGN-COV2 is expected to increase by at least three and a half times, substantially increasing the number of doses available to patients in the U.S. and around the world.|
|Links||Casirivimab and Imdevimab Information Page
November 21, 2020: Regeneron’s REGEN-COV2 Receives Emergency Use Authorization
REGN-COV2 antibody cocktail prevents and treats SARS-CoV-2 infection in rhesus macaques and hamsters
Regeneron Data and Findings on Phase 2 Trials
Regeneron Brief Explaining Monoclonal Antibodies vs. Vaccines
AstraZeneca has developed a Long Acting Antibody (LAAB) combination, has a production contract with the Federal government, and received $486M on October 12th to test if its COVID-19 antibody cocktail can provide 12 months of protection.
|Description||AstraZeneca’s long-acting antibody (LAAB) combination, AZD7442 have been engineered with AstraZeneca’s proprietary half-life extension technology to increase the durability of the therapy for six to 12 months following a single administration. The combination of two LAABs is also designed to reduce the risk of resistance developed by the SARS-CoV-2 virus. LAABs mimic natural antibodies and have the potential to treat and prevent disease progression in patients already infected with the virus, as well as to be given as a preventative intervention prior to exposure to the virus. A LAAB combination could be complementary to vaccines as a prophylactic agent, e.g. for people for whom a vaccine may not be appropriate or to provide added protection for high-risk populations. It could also be used to treat people who have been infected.|
|How Administered||Liquid solution with intravenous administration via medical staff.|
|Stage||Phase 2 Trials completed. Now in accelerated Phase 3 trials for targeted for EUA clearance by end of year. Phase III clinical trials in more than 6,000 participants at sites in and outside the US that are due to begin in the next weeks.|
|Efficacy||Phase 2 clinical trial data not yet published. In a recent Nature publication, the LAABs were shown in pre-clinical experiments to block the binding of the SARS-CoV-2 virus to host cells and protect against infection in cell and animal models of disease.|
|Safety||Phase 2 clinical trial data not yet published.|
|Current Production||Currently restricted to clinical trials.|
|Production Capacity||The Company has received support of around $486m from the US Government for the development and supply of AZD7442 under an agreement with the Biomedical Advanced Research and Development Authority (BARDA). AstraZeneca plans to supply up to 100,000 doses starting towards the end of 2020 and the US Government can acquire up to an additional one million doses in 2021 under a separate agreement.|
|Links||AJMC: US Signs Deal With AstraZeneca to Develop, Make COVID-19 Antibody Treatment
HHS: Trump Administration Expands Collaboration with AstraZeneca to Develop and Manufacture an Investigational Monoclonal Antibody to Prevent COVID-19
AZ: COVID-19 Long-Acting AntiBody (LAAB) combination AZD7442 rapidly advances into Phase III clinical trials
Nature: Potently neutralizing and protective human antibodies against SARS-CoV-2
Vir Biotechnology and GlaxoSmithKline
Vir Biotechnology, Inc. and GlaxoSmithKline plc announced on October 6, 2020 the global expansion to Phase 3 of the COMET-ICE (COVID-19 Monoclonal antibody Efficacy Trial – Intent to Care Early) study evaluating VIR-7831 for the early treatment of COVID-19 in patients who are at high risk of hospitalization. VIR-7831 (also known as GSK4182136) is a fully human anti-SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus-2) monoclonal antibody that was selected based on its potential to neutralize the virus, kill infected cells, provide a high barrier to resistance, and achieve high concentrations in the lungs (one of the major sites of infection). Following a positive assessment of unblinded safety data from the lead-in portion of the trial by an Independent Data Monitoring Committee on September 30, 2020, the COMET-ICE registrational study will now expand globally to additional sites in North America, South America and Europe.
In addition to its partnership with Vir Biotechnology for antibody-based drugs, GlaxoSmithKline is a leader in partnership with Sanofi in vaccine development and production, as well as rapid testing.
Using its established hyperimmune platforms, Emergent is developing two investigational plasma-based treatments – COVID-19 Human Immune Globulin (COVID-HIG) and COVID-Equine Immune Globulin (COVID-EIG). COVID-HIG is being developed as a human plasma-derived therapy candidate with $14.5 million in HHS funding and will be evaluated in two studies, inclusive of INSIGHT-13 (ITAC), of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, for potential treatment of COVID-19 in severe hospitalized and high-risk patients. With $34.6 million in funding from the Department of Defense’s Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense, and in collaboration with the Mount Sinai Health System and ImmunoTek Bio Centers, COVID-HIG will also be evaluated for post-exposure prophylaxis in populations at high risk of COVID-19, such as front-line health care workers and the military. COVID-EIG is being developed as an equine plasma-derived therapy candidate for potential treatment of severe disease in humans. Both candidates are anticipated to be in clinical studies in 2020 and 2021.
Adagio Therapeutics / Adimab
Adagio Therapeutics is very much a ‘Dark Horse’ – but a very interesting one! Adagio Therapeutics was spun out of Adimab in July, 2020 based on the work of the Prometheus project to develop a ‘Super Antibody’ for COVID-19. Adimab has established a very impressive track record for successful rapid development of antibody-based drugs over the last decade, including most recently and notably during the last Ebola outbreak. Since 2009, Adimab has partnered with over 75 pharmaceutical and biotechnology companies, generating more than 340 therapeutic programs, of which 40 have entered clinical trials
The Adimab team developed and optimized antibodies that are broadly protective against SARS-CoV-2, SARS-CoV-1 and two additional circulating bat coronaviruses scientists are actively monitoring. The company believes these neutralizing antibodies will match the potency and coverage of competing SARS-CoV-2 antibody programs while also offering protection against additional pathogenic coronaviruses that have yet to emerge.