Last autumn, data from the phase II portion of Lilly’s Blaze-1 trial, in mild to moderate Covid-19, pointed to the ability of bamlanivimab plus etesevimab to reduce viral load and hospital visits. A new cut from Blaze-1 released today concerns harder endpoints and a much larger dataset.
Among 1,035 patients in the phase III portion of the trial, a 2,800mg dose of both MAbs significantly cut Covid-19-related hospitalisations and deaths versus placebo. There were 11 of these events (2.1%) in patients taking the combo and 36 (7%) in placebo recipients, which Lilly stated represented a "70% risk reduction" (p=0.0004), and hit the study’s primary outcome.
Crucially, all 10 patient deaths were in the placebo arm. Patients in the study were at high risk of progressing to severe Covid-19 and/or hospitalisation.
Bamla alone is already authorised in the US for emergency use for high-risk patients with mild-to-moderate Covid-19, but the combo is still awaiting the FDA’s decision on an EUA submission made last year. Given the trial’s hit, and particularly the mortality benefit, this is surely now odds-on, but in the meantime Blaze-1 will continue to accrue up to 3,300 patients.
Lilly is also working with the FDA to cut infusion times for these large doses of the antibodies. It is hoping to gain authorisation for a 16-minute infusion, much faster than the currently authorised time of an hour. This ought to simplify administration and reduce the burden on the healthcare system.
Lilly also said that the Blaze-4 trial, in the outpatient setting, showed that lower doses, including bamla 700mg and etesevimab 1,400mg together, had similar effects on Covid-19 viral load to the 2,800mg combo. No actual figures were released.
The trial’s primary outcome measure is the percentage of participants with a viral load greater than 5.27 seven days after treatment, though the rate of Covid-19-related hospitalisation, ER visit or death will also be tracked.
Lilly plans to explore even lower doses of bamlanivimab and etesevimab together, since lower doses can maximise supply to treat more patients, reduce infusion times and possibly even allow subcutaneous dosing.
|Blazing a trail: Lilly's trials of bamlanivimab|
|Blaze-1||Phase II/III, bamla (LY-CoV555) + etesevimab (LY-CoV016) in mild-to-moderate Covid-19||2,450||Primary endpoint hit: 70% reduction in hospitalisation or death|
|Blaze-2||Phase III, bamla + etesevimab in preventing Covid-19 in nursing home residents and staff||5,000||Primary endpoint hit: 57% reduction in risk of developing Covid-19|
|Blaze-4||Phase II, bamla + etesevimab in mild-to-moderate Covid-19||700||Initial data reported Jan 2021; trial ongoing|
|Blaze-5||Phase II, bamla monotherapy in mild-to-moderate Covid-19||3,000||Ongoing, data due 2021|
|Source: EvaluatePharma, company statements, clinicaltrials.gov.|