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SARS-CoV-2 Neutralizing Antibody LY-CoV555 in COVID-19 Outpatients
Quick Takes
- Only patients who received the 2800 mg of LY-CoV555 had a statistically significant decrease in viral load at day 11 compared to placebo.
- LY-CoV555 was associated with earlier symptom improvement and potentially a decrease in hospitalization.
- The phase 3 clinical trial assessing the effectiveness of ACTIV-3 was closed following a recommendation by the data safety monitoring board due to lack of clinical benefit.
Study Questions:
In outpatients with mild to moderate coronavirus disease 2019 (COVID-19), does treatment with viral-neutralizing monoclonal antibodies reduce viral load?
Methods:
BLAZE-1 is an industry-sponsored (Eli Lilly) multicenter, randomized, double-blind, placebo-controlled single-dose trial assessing the effectiveness of a single intravenous infusion of LY-CoV555 in reducing viral load at day 11 in outpatients with positive testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with mild to moderate symptoms. Either LY-CoV555 or placebo was administered within 3 days after positive results on SARS-CoV-2 testing. LY-CoV555 is a potent antispike neutralizing monoclonal antibody that binds with high affinity to the receptor-binding domain of SARS-CoV-2. This manuscript relays interim results of patients who received doses of 700 mg, 2800 mg, 7000 mg, and placebo. The primary outcome was the change from baseline in the SARS-CoV-2 viral load at day 11 (±4 days) after positive results on testing.
Results:
A total of 467 patients underwent randomization to receive either LY-CoV555 (317 patients) or placebo (150 patients), and the patients in the LY-CoV555 group were assigned to one of three dose subgroups: 700 mg (101 patients), 2800 mg (107 patients), or 7000 mg (101 patients). The median age of the cohort was 45 years, of whom close to one third were ≥65 years. Overall viral load decreased in all groups by day 11. Only the patient group which received the 2800 mg dose of LY-CoV555 had a statistically significant reduction in viral load compared to placebo (−0.53; 95% confidence interval, −0.98 to −0.08; p = 0.02). At day 29, the percentage of patients who were hospitalized with COVID-19 was 1.6% (5 of 309 patients) in the LY-CoV555 group and 6.3% (9 of 143 patients) in the placebo group. Patients in the LY-CoV555 group had earlier improvement in symptoms compared to the placebo group. There were no serious adverse events in the LY-CoV555 group.
Conclusions:
At day 11 post-testing for SARS-CoV-2, only patients who received the 2800 mg dose had a significant decrease in viral load compared to placebo.
Perspective:
The choice of a day 11 viral load as the primary outcome may not have been the most appropriate, given many patients with mild COVID-19 would have recovered by then, as evidenced by the reduction in viral loads across all groups. Secondary analyses do highlight some promising findings, with significant decreases in viral loads at 3 days, earlier improvement in symptoms, and decrease in hospitalizations. However, it is unclear whether the minor differences in soft outcomes warrant the costs involved in producing and administering monoclonal antibodies to a potentially large patient population who will mostly do well and recover with conservative medical management. Despite the lack of a strong rationale for cost-effectiveness of such a therapy in this patient population, a phase 3 trial (ACTIV-3) was underway. That trial has stopped enrolling new patients given interim analysis showed no significant clinical benefit for LY-CoV555.
Clinical Topics: COVID-19 Hub, Prevention, Novel Agents
Keywords: Antibodies, Blocking, Antibodies, Monoclonal, Antibodies, Neutralizing, Coronavirus, COVID-19, Infusions, Intravenous, Outpatients, Primary Prevention, severe acute respiratory syndrome coronavirus 2, Viral Load
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