Both Eli Lilly and Regeneron have filed requests to the FDA for Emergency Use Authorization (EUA) for their antibody-based treatments for COVID-19.
Regeneron’s EUA request comes after the success of its antibody cocktail in treating President Donald Trump this past week. Trump has since called the cocktail a “cure” for COVID-19 and a “miracle from god.” Phase 1/2/3 clinical trials of REGN-COV2 have showed it reduces viral load and time to alleviate symptoms in non-hospitalized patients with COVID-19.
Also on Wednesday, Eli Lilly submitted an EUA request for its LY-CoV555 monoclonal antibody treatment, which was recently identified from a blood sample taken from one of the first U.S. patients to recover from COVID-19. Next month, the pharmaceutical giant anticipates submitting a second EUA for its combination therapy featuring two SARS-CoV-2 neutralizing antibodies.
Regeneron’s clinical trials
Regeneron has not released the full findings of its clinical trials yet, but the “key data” released early last week indicates REGN-COV2 reduces viral load through day 7 for COVID-19 patients.
REGN-COV2 is a combination of two monoclonal antibodies (REGN10933 and REGN10987) that was designed specifically to block infectivity of SARS-CoV-2. The antibodies 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.
The ongoing, randomized, double-blind trial measures the effect of adding a low dose of REGN-COV2 (2.4 g) as well as a high dose (8 g) to standard care compared with a placebo. While Regeneron has reportedly enrolled 2,000 patients for the trial, the results associated with this data only reflect the first 275 people.
In the trial, both the high and low doses reduced viral loads through day 7, with a greater reduction seen in patients treated with the high dose, which is the treatment Trump received. Those patients who presented with higher viral loads than normal experienced a 50% to 99% reduction compared to placebo patients. The same proved true regarding symptom alleviation—the trial found the median time to symptom alleviation was 13 days in placebo, 8 days in high dose and 6 days in low dose. The vast majority of the trial patients did not require ER visits or hospitalization.
Regeneron says both doses were well-tolerated, with few infusion reactions and only 1 severe adverse event in a low dose patient.
In addition to this trial in non-hospitalized patients, REGN-COV2 is also being studied in a Phase 2/3 clinical trial in hospitalized COVID-19 patients, a Phase 3 open-label RECOVERY trial of hospitalized patients in the UK and a Phase 3 trial for the prevention of COVID-19 in household contacts of infected individuals.
Eli Lilly’s clinical trials
Eli Lilly’s LY-CoV555 is a 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, neutralizing the virus and potentially preventing and treating COVID-19. Eli Lilly is seeking its use in higher-risk patients who have been recently diagnosed with mild-to-moderate coronavirus.
The antibody, which hails from a blood sample taken from one of the first U.S. patients to recover from COVID-19, was identified relatively recently by AbCellera and the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. Eli Lilly then rapidly developed the antibody in less than three months, before entering it into clinical trials.
A Phase 1 study of hospitalized patients is currently underway, with long-term follow-up ongoing. Meanwhile, the 800-patient Phase 2 study, referred to as BLAZE-1, is multi-faceted—assessing the efficacy and safety of LY-CoV555 alone, as well as in combination with the LY-CoV016 antibody.
LY-CoV016 is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain looking to block the binding of the virus to the ACE2 host cell surface receptor.
The randomized, double-blind, placebo-controlled monotherapy arm of the trail is studying three doses of LY-CoV555 (700 mg, 2800 mg and 7000 mg) versus placebo in mild-to-moderate recently diagnosed COVID-19 patients. Concurrently, the combination arm is studying LY-CoV555 2800 mg plus LY-CoV016 2800 mg versus placebo.
According to the trial results, combination therapy reduced viral levels at day 3 and day 7—a time when higher viral loads are typically seen with standard care. At day 7, for example, only 3 percent of patients who received combination therapy had a high viral load compared with 21 percent of placebo patients.
Patients who received combination therapy also showed symptom improvement as early as three days after dosing. In fact, those who received the therapy were 85% less likely to require the ER or hospitalization than placebo patients—0.9% compared with 5.8%. Reported side effects were mild, including infusion reactions and hypersensitivity.
Eli Lilly said it anticipates having data to support a biologics license application (BLA) submission for combination therapy as early as Q2 2021. The pharmaceutical company also said it will publish the monotherapy and combination therapy data in peer-reviewed journals “as soon as possible.”
Meeting demand
Regulatory approval is only half the battle—the second part of the equation involves producing enough medication to follow through on treatment demands.
In a statement, Regeneron said initial doses of REGN-COV2 would be free under the EUA agreement. Currently, there are enough doses for approximately 50,000 patients, and the pharmaceutical company expects to have doses available for an additional 250,000 patients within the next few months.
Thinking ahead, Eli Lilly said it invested in “large-scale manufacturing of both antibodies at risk, even before data demonstrated their potential to become a meaningful therapeutic option for COVID-19.” The company anticipates it could supply up to 1 million doses of 700 mg LY-CoV555 monotherapy in Q4 2020, with 100,000 available this month pending EUA. Lilly projects to have 50,000 doses of the combination therapy available in Q4 2020, with the stockpile substantially increasing in Q1 2021.