TrialSite News reported on Aug 22 that a South Texas trial site location reported growing confidence in a SARS-CoV-2 neutralizing antibody-based investigational product developed by Eli Lilly (Lilly) called LY-CoV555. Developed with the help of powerful discovery technology from University of Vancouver spin-off venture AbCellera and help from National Institutes of Allergy and Infectious Diseases (NIAID), LY-CoV555 has been under investigation in the BLAZE-1 clinical trial. Now Lilly reports that proof-of-concept data from an interim analysis of the study reveals that those patients administered LY-CoV555 show a reduced rate of hospitalization. This data is the result of an interim analysis and requires further data for confirmation. Furthermore this is data directly from a pharmaceutical company and final data would be submitted for peer review. However data is sufficient enough that not only is Lilly moving toward peer review with the interim analysis but also the Indianapolis-based pharmaceutical company has partnered with biotech Amgen for scaling up production of LY-CoV555 in a signal that the company will go for either an emergency use authorization or file an application to the U.S. FDA to market the drug—or both.
TrialSite News offers a brief breakdown of this Lilly update.
What is BLAZE-1?
BLAZE-1 is a randomized, double-blind, placebo-controlled Phase 2 clinical trial.
What is LY-CoV555?
LY-CoV555 is a potent, 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, thus neutralizing the virus, potentially preventing and treating COVID-19. LY-CoV555 emerged from the collaboration between Lilly and AbCellera to create antibody therapies for the prevention and treatment of COVID-19. Lilly scientists rapidly developed the antibody in less than three months after it was discovered by AbCellera and tested by the scientists at the National Institute of Allergy and Infectious Diseases (NIAID) Vaccine Research Center. It was identified from a blood sample taken from one of the first U.S. patients who recovered from COVID-19.
Why does TrialSite claim confidence was building at Crossroads?
On Aug 22, TrialSite reported that Crossroads Clinical Research, a trial site based in Corpus Christi and Victoria, Texas and participating in BLAZE-1 shared that the trial was coming along nicely. A research coordinator at the trial site organization shared with the media a high degree of confidence involving the advanced investigational drug.
What were the four groups in the first part of BLAZE-1?
BLAZE-1 initially enrolled mild-to-moderate recently diagnosed COVID-19 patients across four groups (placebo, 700 mg, 2800 mg and 7000 mg).
How has BLAZE-1 morphed?
Now BLAZE-1 has included a new monoclonal antibody licensed from Shanghai Junshi Bioscience. In one arm is LY-Cov555 by itself and another arm combines LY-CoV555 and the Junshi Bioscience monoclonal antibody called LY3832479 or LY-CoV016.
What is the primary endpoint for BLAZE-1 thus far?
The primary endpoint from baseline in viral load at day 11, was met at 2800 mg dose level, but not the others. E.g. 700 mg and 7000 mg did not reduce hospitalization. Interestingly by day 11 most patients, including those receiving the placebo demonstrated near complete viral clearance.
Does LY-CoV555 help with viral clearance?
It appears that is the case. Lilly reported that viral clearance was observed at an earlier time point (day 3) and reduced the proportion of patients with persistently high viral load at later time points.
What is overall positive impact data thus far?
LY-CoV555 reduces patient hospitalization based on the interim analysis. For example, 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 this limited population.
Lilly reported that most hospitalizations occurred in patients with underlying risk factors (e.g. age or BMI), suggesting a more pronounced treatment effect for patients in these higher-risk groups.
Is this data 100% conclusive?
No. This is the result of an interim analysis from the pharmaceutical company itself. Ultimately, Lilly needs to continue the study to confirm these findings. Then they will need to submit findings to peer review for confirmation.
What are other positive observations thus far?
All across all treatment groups, no patients progressed to mechanical ventilation status or died. Moreover, exploratory analyses suggest a greater, more rapid improvement in symptoms for patients administered LY-CoV555 versus placebo, supporting the hospitalization effect.
What are Lilly’s next steps?
Lilly will seek to publish these results of this interim analysis in a peer-reviewed journal and discuss appropriate next steps with regulators.
In parallel, BLAZE-1 continues involving the ongoing testing of LY-CoV555 in combination with the Junshi (China) antibody called LY-CoV016—which binds to a different epitope in the SARS-CoV-2 spike region. The BLAZE-01 trial continues on.
Are these monoclonal antibodies safe?
It would appear so. At least thus far, LY-CoV555 is well-tolerated with no drug-related serious adverse events reported.
Is there evidence that Lilly will move for either emergency use authorization or approval by FDA?
Well, they just announced a manufacturing partnership with Amgen to produce LY-CoV555. According to Lilly chief scientific officer and president of Lilly Research Laboratories Daniel Skovronsky, MD, PhD, “Based on our initial clinical studies, we believe that virus neutralizing antibodies, including LY-CoV-555 could play an important role in the fight against COVID-19.” Emphasizing production scale, the chief scientific officer continued, “Increasing the manufacturing capacity of our neutralizing antibodies through this collaboration with Amgen is a crucial next step, and together we hope to be able to produce many millions of doses even next year.”
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