COVID-19 Antibody Therapies
This month, last year, COVID-19 was declared a national emergency in the United States. At that time, it seemed improbable that a vaccine would be developed and approved for use by the end of the year. When the improbable happened, there was no doubting it as our favorite scientific breakthrough of 2020. With vaccines being at the center of public attention today, we think it’s important to not let that attention overshadow the importance of treating patients with COVID-19. One therapeutic path we like to follow is monoclonal antibody therapy, as it has proven itself to be a potential lifesaving treatment [1, 2]. Check out our previous blog post for a quick refresher on the difference between vaccines and antibody therapeutics.
While the pharmacologic treatment of hospitalized COVID-19 patients primarily includes dexamethasone, remdesivir, or a combination of the two; these drugs are not recommended for treatment of non-hospitalized patients, including those who are at high risk of disease progression . Monoclonal antibodies, on the other hand, are a highly recommended treatment for non-hospitalized patients who are at high risk of disease progression and eventual hospitalization . To date, three monoclonal antibody therapies have been granted emergency use authorizations by the FDA [5, 6, 7]. All of these may be used on non-hospitalized, high-risk patients who are 12 years of age or older and weigh at least 40 kg (90 lbs).
Early on in the pandemic, one of the avenues investigated for potential therapeutic value was convalescent plasma therapy, which involves infusing patients with blood plasma from donors who have recovered from the disease in question . This plasma, separated from blood by a specialized apheresis machine during a blood donation, is rich in antibodies, including those designed by the donor’s immune system to fight off the SARS-CoV-2 virus. While each plasma donation has the potential to save the lives of up to three COVID-19 patients, it also holds the potential to aid in the development of new antibody therapeutics, saving countless lives [9,10]. The three COVID-19 therapeutics authorized for use by the FDA were developed, in part, using convalescent plasma. In comparison to convalescent plasma, these antibody therapies are more expensive and labor intensive to produce; however, they are more effective, as they are consistent and contain high levels of antibodies that only target SARS-CoV-2 .
Bamlanivimab, the first monoclonal antibody treatment for COVID-19, was authorized under emergency use by the FDA on November 09, 2020 . This treatment was the result of a collaboration between AbCellera and Eli Lilly and was derived from the plasma of one of the earliest recovered COVID-19 patients. An interim analysis of a BLAZE-1 clinical trial showed that Bamlanivimab significantly reduced viral load and showed a 1.6% hospitalization rate in the treatment group versus a 6.3% rate in the placebo group . In a separate BLAZE-2 prevention study, Bamlanivimab demonstrated its preventive capacity, as it reduced the risk of contracting COVID-19 by up to 80% for residents and staff of the various long-term care facilities involved in the trial .
Casirivimab and Imdevimab
On November 21, 2020, the monoclonal antibody combination of casirivimab and imdevimab, also known as REGN-COV2 antibody cocktail, was authorized by the FDA . In trials leading to the authorization, 799 COVID-19 positive individuals received 1200mg of each antibody, 4000mg of each antibody, or a placebo. Results of the study concluded that patients treated with the antibody combinations had a 3% chance of developing severe symptoms and becoming hospitalized compared to a 9% chance for those taking the placebo . In a preventive study, the REGN-COV2 antibody cocktail showed potential as a passive vaccine, as it showed a 100% prevention rate of symptomatic COVID-19 in a group of 186 individuals at high risk of contracting the virus due to confirmed cases within their household .
Bamlanivimab and Etesevimab
On February 09, 2021, the FDA authorized the use of Bamlanivimab in combination with Etesevimab. Results of initial clinical trials showed a significant reduction of 70% in COVID-19-related hospitalization and death compared to the placebo group. No deaths were reported in the group of 518 patients who received the combination . Following the authorization, Bamlanivimab and Etesevimab trials have continued to further assess the efficacy of the pair. Recent data has shown a greater risk reduction than initially realized, with a reported 87% reduction in hospitalization and death .
Antibody Therapies In Development
With the proven effectiveness of monoclonal antibody therapy for treatment of patients with COVID-19, much interest remains in developing new antibody therapeutics or assessing existing antibodies as potential COVID-19 therapeutics. To date, over 40 clinical trials have been opened to assess anti-SARS-CoV-2 monoclonal antibodies. These studies are assessing currently authorized and newly developed antibody therapies, as well as antibody therapeutics that are approved for treatment of other diseases and have the potential to be repurposed for the treatment of COVID-19 .
With vaccine distribution inching our society closer to normal day by day, a clearly defined end to the pandemic is arguably unclear. And with roughly 30% of Americans not planning on receiving the vaccine, COVID-19 will likely remain in our lives for years to come . COVID-19 related deaths, however, will hopefully become a thing of the past due in part to further development and research of monoclonal antibody therapies.
- Therapeutic Management | COVID-19 Treatment Guidelines (nih.gov)
- Antibody Treatments For COVID-19 Are Worth The Effort, Doctors Say : Shots — Health News : NPR
- Convalescent plasma therapy — Mayo Clinic
- Donate COVID-19 Plasma | FDA
- Coronavirus (COVID-19) Update: FDA Coordinates National Effort to Develop Blood-Related Therapies for COVID-19 | FDA
- Vaccines, convalescent plasma, and monoclonal antibodies for covid-19 | The BMJ
- SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19 | NEJM
- 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 | Eli Lilly and Company
- Regeneron Reports Positive Interim Data with REGEN-COV™ Antibody Cocktail used as Passive Vaccine to Prevent COVID-19 | Regeneron Pharmaceuticals Inc.
- Lilly’s bamlanivimab and etesevimab together reduced hospitalizations and death in Phase 3 trial for early COVID-19 (prnewswire.com)
- World’s Leading Life Science Companies Now Enrolling COMMUNITY, A Global Platform Trial For Hospitalized Patients with COVID-19 (takeda.com)
- Growing Share of Americans Say They Plan To Get a COVID-19 Vaccine — or Already Have | Pew Research Center