The clinical evidence for Bamlanivimab as monotherapy and in combination with Etesevimab consists of a published 5-arm RCT with an adaptive study design (part of the patient population from phase 2 of BLAZE-1) with final results from 592 patients with mild-to-moderate SARS-CoV2 disease in outpatients. In addition, there are unpublished results from the three-arm phase 3 part of BLAZE-1 in high-risk patients with mild to moderate SARS-CoV2 disease.

Clinical efficacy: The results of the published phase 2 part of the BLAZE-1 RCT show that there were no deaths in any of the study groups, either with monotherapy, combination therapy or placebo. In the unpublished phase 3 part of the BLAZE-1 RCT in high-risk patients, there were also no deaths in the combination therapy groups, but 14 deaths in the placebo group, 13 of which were considered COVID-19-related. Both monotherapy and combination therapy significantly reduced hospitalisations and emergency department visits in the phase 2 part of the BLAZE-1 RCT, although the confidence interval shows that there may also be increased admissions (results of high certainty). Dosing had no effect (moderate certainty). In the unpublished phase 3 part of the BLAZE-1 RCT (high-risk patients), a 70% to 87% reduction in hospitalisations and deaths (combined endpoint) was observed.

Safety: Serious adverse events (SAEs) not related to SARS-CoV-2 infection or associated with study drug occurred in 0% of patients in the monotherapy group and in 0.9% of patients with combination therapy. The most commonly reported adverse events (AEs) were nausea (3.0% to 5%) and diarrhoea (1.0% to 5.9%).

Conclusion: The main limitation of the phase 2 part of the BLAZE-1 RCT is that post-hoc analyses on high-risk patients (i.e. ≥65 years or BMI ≥35) were only conducted in a small group. However, according to the regulatory authorities EMA and FDA in the EU and US, the current indication for Bamlanivimab is for those COVID-19 patients with mild or moderate disease but at high risk of progression to severe disease. The unpublished results must be interpreted with caution until a peer-reviewed publication is available. A conclusive assessment is not possible based on the current data.