Eli Lilly and Company (NYSE: LLY) announced that proof of concept data from an interim analysis of the BLAZE-1 clinical trial reveals a reduced rate of hospitalization for patients treated with LY-CoV555. An ongoing randomized, double-blind, placebo-controlled Phase 2 study reveals centers on the investigational product known as LY-CoV555. Developed thanks to a partnership affording access to powerful drug discovery technology from AbCellera, in combination with dedicated Lilly scientists working day and night starting back in the early Spring, this potent monoclonal antibody demonstrates real promise as a regimen targeting both COVID-19 prevention and treatment.
The ongoing clinical trial evaluated LY-CoV555, a SARS neutralizing antibody, for the treatment of symptomatic COVID-19 in the outpatient setting. Enrolling mild-to-moderate recently diagnosed COVID-19 patients across four groups (Placebo, 700 mg, 2800 mg, and 7000 mg).
The prespecified primary endpoint, change from baseline in viral load at day 11, was met at the 2800 mg dose level, but not the others. Most patients, including those receiving placebo, demonstrated near complete viral clearance by day 11. Additional analyses of viral data evidenced that LY-CoV555 improved viral clearance at an earlier time (day 3) and reduced the proportion of patients with persistently high viral load at later time point.
Correlation to Hospitalization or ER Visit Data
Lilly reports that the current biomarker data correlates with LY-CoV555 positive impact on the prespecified endpoint of COVID-19-related hospitalization or ER visit data outcomes. This endpoint occurred in 1.7 percent (5.302) of LY-CoV555 patients, pooled across dose groups, as compared to 6 percent (9/150) of placebo patients, which corresponds to a 72 percent risk reduction in the limited population.
Most study hospitalizations occurred in patients with underlying risk factors (age or BMI), suggesting a more pronounced treatment effect for patients in these higher-risk groups. Ongoing studies will seek to confirm the finding.
Promising Interim Result Data Point
Importantly, across all treatment groups (including placebo), no patients progressed to mechanical ventilation or died. Exploratory analysis indicated a more rapid improvement in symptoms for patients treated with LY-CoV555 versus placebo, supporting the hospitalization effect.
Thus far, LY-CoV555 has been well-tolerated, with no drug-related serious adverse events reported. Treatment emergent adverse events were similar across all dose groups and comparable to placebo.
Viral RNA sequencing demonstrated putative LY-CoV555-resistance variants in placebo and all treatment arms. The rate of resistance variants was numerically higher in treated patients (8 percent) versus placebo (6 percent).
Lilly chief scientific officer Daniel Skovronsky, MD, PhD, Lilly Research Laboratories, reports, “These interim data from BLAZE-1 trial suggest that LY-CoV555, an antibody specifically directed against SARS-oV-2, has a direct antiviral effect and may reduce COVID-19 related hospitalizations.” Of course, TrialSite emphasizes this is incredibly promising in the work needed to ultimately fight COVID-19. Dr. Skovronsky declared, “The results reinforce our conviction that neutralizing antibodies can help in the fight against COVID-19.”
Next Steps: Publish, Discuss with Regulators & Continue BLAZE-1
Lilly will publish the results of the interim analysis in a peer-reviewed journal and discuss next steps with global regulators. Of course, the BLAZE-1 clinical trial continues on as the sponsor tests LY-CoV555 in combination with the other Lilly monoclonal antibody licensed from its Chinese partner Junshi Biosciences. Known as LY-CoV016, this investigational antibody binds to a different epitope in the SARS-CoV-2 spike region. As TrialSite reported today showcasing Columbus, Ohio-based Aventiv Research involvement, the trial is currently enrolling a larger, confirmatory cohort of higher risk patients, testing the ability of the antibody combination to reduce the number of patients with persistently high viral load and reduce COVID-19 hospitalizations.
BLAZE-1 (NCT04427501) is a randomized, double-blind, placebo-controlled Phase 2 study designed to assess the efficacy and safety of LY-CoV555 and LY-CoV016 for the treatment of symptomatic COVID-19 in the outpatient setting. Across all treatment arms this trial will enroll an estimated 800 participants. The monotherapy arms of the trial enrolled mild-to-moderate recently diagnosed COVID-19 patients across four groups. This study can be viewed here.
TrialSite introduced LY-CoV555 in a few different articles but essentially it’s a potent neutralizing IgG1 monoclonal antibody (mAb) targeting the spike protein of SARS-CoV-2. The mAb was actually designed to block or impede viral attachment and penetration into the host cells, hence actually neutralizing SARS-CoV-2 and therefor, offering the patient the prospect of both prevention of COVID-19 as well as a possible treatment option.
LY-CoV555 was the result of a collaboration between Lilly and University of British Columbia spin-off AbCellera to develop monoclonal antibodies targeting COVID-19. Lilly inked a deal with AbCellera back in March 2020 after the impressive Vancouver-based startup secured a partnership with the U.S. government via a DARPA contract. TrialSite reported that thanks to the discovery features of AbCellera, just at the onset of the pandemic, Lilly scientists cranked day and night rapidly developing the antibody in just three months once AbCellera and the Vaccine Research Center at NIAID identified it from a sample from one of the first known infected COVID-19 patients. Born was the first investigational new medicine specifically designed to attack SARS-CoV-2, the virus behind COVID-19. Lilly just announced positive proof of concept data for LY-CoV555.
Ongoing LY-CoV555 Clinical Trials
Lilly has successfully completed enrollment and primary safety assessments of LY-CoV555 in a Phase 1 study of hospitalized patients with COVID-19 (NCT04411628); long-term follow-up is ongoing. A Phase 2 study in people recently diagnosed with COVID-19 in the ambulatory setting (NCT04427501) is ongoing. Lilly recently initiated a Phase 3 study for the prevention of COVID-19 in residents and staff at long-term care facilities (NCT04497987). TrialSite emphasizes the importance of this study based on the high number of deaths at long-term care facilities. Additionally, LY-CoV555 is being tested as part of the NIH-led ACTIV-2 and ACTIV-3 studies of ambulatory and hospitalized COVID-19 patients.
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