Another monoclonal antibody therapy has entered the pandemic fray with the FDA granting emergency use authorization (EUA) for bamlanivimab (LY-CoV555) 700 mg and etesevimab (JS016 or LY-CoV016) 1,400 mg as a cocktail for treating mild to moderate COVID-19 in patients aged 12 and up at high risk for progressing to severe COVID-19 and/or hospitalization.
Three companies, Abcellera Biologics Inc., Eli Lilly and Co. and Junshi Biosciences Co. Ltd., had a hand in the development. Abcellera and Lilly discovered and developed bamlanivimab while Lilly licensed etesevimab from Shanghai-based Junshi, which developed the recombinant fully human monoclonal antibody with the Institute of Microbiology, Chinese Academy of Science.
The authorization follows the EUA granted to Regeneron Pharmaceutical Inc. and Roche Holding AG’s monoclonal antibody cocktail REGEN-COV (casirivimab and imdevimab) on Nov. 21. The U.S. Department of Health and Human Services and the Department of Defense said it will purchase all finished doses supplied by June 30, as many as 1.25 million doses, for up to $2.625 billion.
REGEN-COV, used as a passive vaccine, is designed to provide immediate short-term passive immunity in preventing COVID-19 in people at high risk of infection due to household exposure to a COVID-19 patient.
Lilly and Amgen Inc. said they will manufacture as many as 1 million doses of etesevimab by mid-2021. There are 100,000 doses available now and another 150,000 doses will be manufactured by the end of the first quarter of 2021. Lilly said it expects to manufacture up to a million doses by mid-2021.
Even with reduced infusion times, the therapy has to compete with COVID-19 vaccines that are more quickly administered as shots. The Abcellera-Lilly-Junshi cocktail is to be administered as a single I.V. to patients who test positive and within 10 days of showing symptoms. The FDA, in the EUA, did step away from its previously authorized 60-minute infusion time to tab bamlanivimab dosing alone at 16 minutes and bamlanivimab and etesevimab together at 21 minutes.
Etesevimab binds to the SARS-CoV-2 surface spike protein receptor binding domain, blocking the virus from binding to the ACE2 host cell surface receptor. Bamlanivimab is designed to neutralize the virus by blocking viral attachment and cell entry.
The EUA is based on phase III data, released in late January, from the phase III Blaze-1 study, which met its primary and key secondary endpoints by decreasing the risk of hospitalizations or death by 70%. The clinical trial also showed improvement in the change from baseline to day seven in SARS-CoV-2 viral load, time to sustained symptom resolution and COVID-related hospitalization. Ten deaths involved patients taking placebo.
Bamlanivimab already had an EUA, granted in November, for treating mild to moderate disease in high-risk patients. The authorization was based on Lilly’s phase II Blaze-1 study, a randomized, double blind, placebo-controlled investigation of outpatients with mild to moderate COVID-19. Viral load limits were reduced, according to the data, along with rates of symptoms and hospitalization.
In addition to battling the clock for infusion times, there are other issues surrounding monoclonal antibodies for treating COVID-19. The FDA, in granting the November EUA, noted monoclonal antibodies “may be associated with worse clinical outcomes” when administered to hospitalized COVID-19 patients needing high-flow oxygen or mechanical ventilation. The FDA also warned about hypersensitivity that includes anaphylaxis and infusion-related reactions in patients.
The U.S. government bought 300,000 doses and said American patients will have no out-of-pocket costs though health care facilities may charge to administer the treatment.
Bamlanivimab is also a moneymaker. As of Feb. 3, it had notched worldwide revenues of $871.2 million for Lilly in the fourth quarter of 2020.
There are other COVID-19 antibody therapies in production. Vir Biotechnology Inc. and Lilly are combining bamlanivimab and VIR-7831, also a monoclonal antibody, in the ongoing phase II Blaze-4 study, enrolling about 200 low-risk patients with mild to moderate COVID-19. Adagio Therapeutics Inc. recently released in vitro and in vivo data on its monoclonal antibody COVID-19 therapy, ADG-2, showing similar or higher potency against SARS-CoV-2 compared to other monoclonal antibodies in clinical development and strong binding to all known SARS-CoV-2 variants.
In all, according to BioWorld stats, there are 670 COVID-19 therapeutics being developed.
Others in the clinic investigating monoclonal antibody therapies include Idbiologics Inc. in a phase I study, a multi-school collaboration of Columbia University, NYU Langone Health, Vitaeris Inc., Cedars-Sinai Medical Center, Johns Hopkins University and the Medical University of Vienna are in a phase II study, Brii Biosciences and TSB Therapeutics (Beijing) Co. Ltd. are in a phase II, as is Adrenomed AG, of Hennigsdorf, Germany.
On Jan. 27, the U.S. Department of Defense awarded Just-Evotec Biologics Inc. $28.6 million to produce monoclonal antibodies for developing a treatment and/or a prophylaxis for COVID-19.