On Oct. 7, 2020, Eli Lilly announced additional details on its SARS-CoV-2 neutralizing antibody programs – including interim data on combination therapy in recently diagnosed patients with mild-to-moderate COVID-19 – and plans to make these therapies broadly available to patients.

Data from a new interim analysis of the BLAZE-1 clinical trial showed that combination therapy with two of Lilly’s SARS-CoV-2 neutralizing antibodies reduced viral load, symptoms and COVID-related hospitalization and ER visits.

Data from a new interim analysis of the BLAZE-1 clinical trial showed that combination therapy with two of Lilly’s SARS-CoV-2 neutralizing antibodies reduced viral load, symptoms and COVID-related hospitalization and ER visits. The randomized, double-blind, placebo-controlled Phase 2 study evaluated LY-CoV555 and 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 significantly reduced viral load at day 11 (p=0.011), meeting the primary endpoint of the study. Most patients, including those receiving placebo, demonstrated near complete viral clearance by day 11. Further, combination treatment reduced viral levels at day 3 (p=0.016) and day 7 (p<0.001)—earlier time points during the course of infection when higher viral loads are typically seen. Combination therapy also significantly reduced the time-weighted average change from baseline from day 1 to 11. An exploratory analysis showed that the proportion of patients with persistent high viral load at day 7 for combination therapy was lower (3.0 percent) versus placebo (20.8 percent), corresponding to a nominal p value of p<0.0001 without multiplicity adjustment. No emergent putative resistance variants have been observed thus far in patients treated with combination therapy.

Combination therapy 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 LY-CoV555 monotherapy. The rate of COVID-related hospitalization and ER visits was lower for patients treated with combination therapy (0.9 percent) versus placebo (5.8 percent), a relative risk reduction of 84.5 percent (p=0.049). This was also similar to observations for LY-CoV555 monotherapy.

Combination therapy has been generally well tolerated with no drug-related serious adverse events. In LY-CoV555 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 LY-CoV555 monotherapy and combination therapy.

Lilly is working to publish the monotherapy and combination therapy data in peer-reviewed journals as soon as possible.