Data from a new interim analysis of the BLAZE-1 clinical trial has shown that combination therapy with two SARS-CoV-2 neutralizing antibodies has reduced viral load, symptoms and COVID-related hospitalization and ER ( Emergency Room ) visits.
The randomized, double-blind, placebo-controlled phase 2 study evaluated Bamlanivimab ( LY-CoV555 ) and Etesevimab ( LY-CoV016 ), which bind complementary regions of the SARS-CoV-2 spike protein, for the treatment of symptomatic COVID-19 in the outpatient setting.
The combination cohort enrolled recently diagnosed patients with mild-to-moderate COVID-19, who were assigned to 2800 mg of each antibody ( n=112 ) or placebo ( n=156 ).
The combination therapy has significantly reduced viral load at day 11 ( p=0.011 ), meeting the primary endpoint of the study.
Most patients, including those receiving placebo, have demonstrated near complete viral clearance by day 11.
Further, combination treatment has reduced viral levels at day 3 ( p=0.016 ) and day 7 ( p less than 0.001 ), earlier time points during the course of infection when higher viral loads are typically seen.
Combination therapy has also significantly reduced the time-weighted average change from baseline from day 1 to 11.
An exploratory analysis has shown that the proportion of patients with persistent high viral load at day 7 for combination therapy was lower ( 3.0% ) versus placebo ( 20.8% ), corresponding to a nominal p value of p less than 0.0001 without multiplicity adjustment.
No emergent putative resistance variants have been observed thus far in patients treated with combination therapy.
Combination therapy has also met prespecified clinical endpoints, including the time-weighted average change from baseline in total symptom score from day 1 to 11 ( p=0.009 ).
The improvement in symptoms was observed as early as three days after dosing and was similar in magnitude and timing to improvements previously seen with Bamlanivimab monotherapy.
The rate of COVID-related hospitalization and ER visits was lower for patients treated with combination therapy ( 0.9% ) versus placebo ( 5.8% ), a relative risk reduction of 84.5% ( p=0.049 ).
This was also similar to observations for Bamlanivimab monotherapy.
Combination therapy has been generally well tolerated with no drug-related serious adverse events.
In Bamlanivimab monotherapy studies there have been isolated drug-related infusion reactions or hypersensitivity that were generally mild ( two reported as serious infusion reactions, all patients recovered ).
Treatment emergent adverse events were comparable to placebo for both Bamlanivimab monotherapy and combination therapy.
Bamlanivimab is a potent, neutralizing IgG1 monoclonal antibody 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.
The primary safety assessments of Bamlanivimab in a phase 1 study of hospitalized patients with COVID-19 and long-term follow-up is ongoing.
A phase 2 study in people recently diagnosed with COVID-19 in the ambulatory setting ( BLAZE-1 ) is ongoing.
A phase 3 study for the prevention of COVID-19 in residents and staff at long-term care facilities ( BLAZE-2 ) has been initiated.
In addition, Bamlanivimab is being tested in the National Institutes of Health-led ACTIV-2 and ACTIV-3 studies of ambulatory and hospitalized COVID-19 patients.
Etesevimab is a recombinant fully human monoclonal neutralizing antibody, which specifically binds to the SARS-CoV-2 surface spike protein receptor binding domain with high affinity and can effectively block the binding of the virus to the ACE2 host cell surface receptor.
Point mutations were introduced into the native human IgG1 antibody to mitigate effector function.
A SARS-CoV-2 challenge study was conducted in rhesus macaques and showed Etesevimab is effective for both prophylactic and therapeutic venues against SARS-CoV-2 infection. ( Xagena )
Source: Lilly, 2020