Lilly provides comprehensive update on progress of SARS-CoV-2 neutralizing antibody programs, including interim data on combination therapy.

Eli Lilly and Company 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. Combination therapy clinical trial data: 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 II 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. the blaze-1 clinical trial (nct04427501) continues to enroll a confirmatory cohort of higher-risk patients who have been recently diagnosed with mild-to-moderate covid-19, testing the ability of the antibody combination to reduce the number of patients with persistent high viral load and reduce covid-related hospitalizations. in addition, lilly is studying lower doses of combination therapy and alternative delivery options in planned or ongoing clinical trials. other ongoing clinical trials include a phase iii study of ly-cov555 monotherapy for the prevention of covid-19 in residents and staff at long-term care facilities (blaze-2, nct04497987). in addition, ly-cov555 monotherapy is being tested in the national institutes of health-led activ-2 and activ-3 studies of ambulatory and hospitalized covid-19 patients. data from these other ongoing trials are not yet available. thus far, over 850 trial participants have been dosed with ly-cov555 (alone or in combination with ly-cov016), contributing to the safety data supporting this potential treatment. open-label pragmatic study in covid-19 outpatients : to generate additional efficacy and safety data, lilly plans to initiate a pragmatic, open-label study in the coming weeks, enrolling patients treated with either monotherapy or combination therapy, with a focus on collecting data regarding hospitalizations, deaths and safety. moving forward, ly-cov555 and ly-cov016 will be referred to as bamlanivimab and etesevimab, respectively.>