Eli Lilly Announces Positive Interim Results from Phase 2 BLAZE-1 Trial of Neutralizing Antibody Combination Therapy for Mild to Moderate COVID-19

On October 8, Junshi Biosciences announced that its global partner, Eli Lilly and Company, released positive interim data from the combination therapy of the SARS-CoV-2 neutralizing antibody JS016 (LY-CoV016) and LY-CoV555 for the treatment of patients recently diagnosed with mild-to-moderate coronavirus disease 2019 (COVID-19).Eli LillyThe company plans to apply for Emergency Use Authorization (EUA) for this combination therapy in patients with mild to moderate COVID-19 in November 2020.

JS016 is a recombinant fully human monoclonal neutralizing antibody that specifically binds with high affinity to the receptor-binding domain (RBD) of the SARS-CoV-2 surface spike protein, effectively blocking the interaction between the virus and the host cell surface receptor ACE2. The development team introduced point mutations into the natural human IgG1 antibody framework to eliminate adverse effects such as tissue damage. A SARS-CoV-2 challenge study conducted in rhesus macaques demonstrated that JS016 exhibits robust efficacy in both the prevention and treatment of SARS-CoV-2 infection. At the outset of the pandemic, Junshi Biosciences collaborated with the Institute of Microbiology, Chinese Academy of Sciences (IMCAS) to jointly develop neutralizing antibodies against SARS-CoV-2. Subsequently, Eli Lilly and Company licensed JS016 from Junshi Biosciences, with Junshi Biosciences leading the development activities in the Greater China region.Eli LillyThe Company leads development activities in other regions worldwide.

LY-CoV555 is a potent, neutralizing IgG1 monoclonal antibody targeting the SARS-CoV-2 spike protein. It was developed to block viral attachment and entry into human cells, thereby neutralizing the virus and potentially preventing and treating COVID-19. LY-CoV555 is derived fromEli LillyThe Company’s research collaboration with AbCellera to develop antibody therapies for the prevention and treatment of COVID-19.

Recently byEli LillyBLAZE-1 Initiated by the CompanyClinical TrialsLatest interim analysis data were released. The results showed that the combination therapy consisting of two SARS-CoV-2 neutralizing antibodies reduced viral load, alleviated symptoms, and decreased COVID-19-related hospitalizations and emergency department visits. This randomized, double-blind, placebo-controlled Phase 2 study aimed to evaluate the efficacy and safety of JS016 (LY-CoV016) in combination with LY-CoV555 for the treatment of outpatients with symptomatic COVID-19. These two neutralizing antibodies bind to complementary regions of the SARS-CoV-2 spike protein. The combination therapy cohort included patients recently diagnosed with mild-to-moderate COVID-19, who were assigned to either the combination treatment group (2800 mg of each antibody) (n=112) or the placebo group (n=156).

Combination therapy significantly reduced viral load on Day 11 (p=0.011), meeting the primary endpoint of the study. The majority of patients, including those receiving placebo, showed near-complete viral clearance by Day 11. Furthermore, combination therapy lowered viral levels on Day 3 (p=0.016) and Day 7 (p<0.001); higher viral loads are typically observed at earlier time points during the course of infection. From Day 1 to Day 11, combination therapy also significantly reduced the time-weighted mean change from baseline. Exploratory analysis revealed that the proportion of patients with persistently high viral load on Day 7 was lower in the combination therapy group (3.0%) than in the placebo group (20.8%). To date, no potential resistance mutations have been observed in patients receiving combination therapy.

Meanwhile, the combination therapy achieved the prespecified clinical endpoints, including the change from baseline in the time-weighted average of the total symptom score from Day 1 to Day 11 (p=0.009). Symptom improvement was observed as early as 3 days after dosing. The rates of COVID-19-related hospitalization and emergency department visits were lower in the combination therapy group (0.9%) than in the placebo group (5.8%), representing an 84.5% relative risk reduction (p=0.049).

The combination therapy was well tolerated, with no drug-related serious adverse events (SAEs) reported. Sporadic drug-related infusion reactions or hypersensitivity reactions observed in the LY-CoV555 monotherapy study were generally mild (two cases were reported as severe infusion reactions, and all patients recovered). Treatment-emergent adverse events (TEAEs) associated with LY-CoV555 monotherapy, JS016 (LY-CoV016), and the combination of JS016 and LY-CoV555 were comparable to those observed with placebo.

According to the press release, Eli Lilly and Company plans to publish the results of this interim analysis in a peer-reviewed journal as soon as possible. Meanwhile, BLAZE-1Clinical TrialsThe confirmatory cohort continues to enroll newly diagnosed high-risk patients with mild-to-moderate COVID-19, aiming to evaluate the benefits of the antibody combination in reducing the number of patients with persistent high viral load and decreasing the risk of COVID-19-related hospitalization. Furthermore,Eli LillyThe company will be in the planned or ongoingClinical Trialsto explore low-dose combination therapy and alternative dosing regimens.

It is worth noting that, based on data from combination therapy and the previously disclosed results of LY-CoV555 monotherapy, Eli Lilly and Company has engaged with global regulatory authorities (includingFDA) regarding potential Emergency Use Authorization. After obtaining additional safety data and securing sufficient manufacturing supply, Eli Lilly and Company expects to submit an EUA application for the combination therapy of JS016 and LY-CoV555 in November 2020. Eli Lilly and Company anticipates obtaining data and submitting a Biologics License Application (BLA) for the combination therapy as early as the second quarter of 2021.Eli LillyThe Company’s communications with global regulatory authorities are ongoing.

In China, Junshi Biosciences has completed a Phase I study evaluating the safety, tolerability, pharmacokinetic profile, and immunogenicity of JS016 in healthy Chinese subjects, and is currently conducting an international, multicenter Phase Ib/II clinical study in patients with COVID-19. Junshi Biosciences also plans to initiate studies in the near future to evaluate the efficacy of JS016 for prevention in populations at high risk of infection.Eli LillyThe Company has also successfully completed a similar Phase 1 clinical study of JS016 in healthy subjects in the United States. To date, JS016 has been well tolerated, with no drug-related serious adverse events (SAEs) observed.BioValleyBioon.com）