Study Design 1
Clinical data supporting this EUA are based on data from 1,433 randomized subjects in the Phase 3 MOVe-OUT trial (NCT04575597). MOVe-OUT is a randomized, placebo-controlled, double-blind clinical trial studying LAGEVRIO for the treatment of non-hospitalized patients with mild-to-moderate COVID-19 who are at risk for progressing to severe COVID-19 and/or hospitalization. Eligible subjects were 18 years of age and older and had one or more pre-defined risk factors for disease progression: over 60 years of age, diabetes, obesity (BMI ≥30), chronic kidney disease, serious heart conditions, chronic obstructive pulmonary disease, or active cancer. The study included symptomatic subjects not vaccinated against SARS-CoV-2 and who had laboratory confirmed SARS-CoV-2 infection and symptom onset within 5 days of randomization. Subjects were randomized 1:1 to receive 800 mg of LAGEVRIO or placebo orally twice daily for 5 days.
Baseline Characteristics 1
At baseline, in all randomized subjects, the median age was 43 years (range: 18 to 90); 17% of subjects were over 60 years of age and 3% were 75 years of age or older; 49% of subjects were male; 57% were White, 5% Black or African American, 3% Asian, 50% Hispanic or Latino. The majority of subjects were enrolled from sites in Latin America (46%) and Europe (33%); 12% were enrolled in Africa, 6% were enrolled in North America and 3% were enrolled in Asia. Forty-eight percent of subjects received LAGEVRIO or placebo within 3 days of COVID-19 symptom onset. The most common risk factors were obesity (74%), over 60 years of age (17%), and diabetes (16%). Among 792 subjects (55% of total randomized population) with available baseline SARS-CoV-2 variant/clade identification results, 58% were infected with Delta (B.1.617.2 and AY lineages), 20% were infected with Mu (B.1.621), 11% were infected with Gamma (P.1), and the remainder were infected with other variants/clades. Overall, baseline demographic and disease characteristics were well balanced between the treatment arms.
Efficacy Results 1
The table below provides the results of the primary endpoint (the percentage of subjects who were hospitalized or died through Day 29 due to any cause). The efficacy results are based on unvaccinated adults who were 18 years of age and older and had one or more pre-defined risk factors for disease progression: over 60 years of age, diabetes, obesity (BMI ≥30), chronic kidney disease, serious heart conditions, chronic obstructive pulmonary disease, or active cancer.
Efficacy Results in Non-Hospitalized Adults with COVID-191,a
aThe determination of primary efficacy was based on a planned interim analysis of 762 subjects. At the interim analysis, 7.3% of patients who received LAGEVRIO were either hospitalized or died through Day 29 (28/385), compared with 14.1% of placebo-treated patients (53/377). The adjusted risk difference was -6.8% with a 95% CI of (-11.3%, -2.4%) and 2-sided p-value = 0.0024.
Adjusted relative risk reduction of LAGEVRIO compared to placebo for all randomized subjects was 30% (95% CI: 1%, 51%).
Analyses are adjusted by the stratification factor of time of COVID-19 symptom onset (≤3 days vs. >3 [4-5] days).
Adverse Reactions from Clinical Studies1
The following adverse reactions have been observed in the clinical study of LAGEVRIO that supported the EUA. The adverse reaction rates observed in these clinical trials cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Additional adverse events associated with LAGEVRIO may become apparent with more widespread use.
Overall, more than 900 subjects have been exposed to LAGEVRIO 800 mg twice daily in clinical trials. The safety assessment of LAGEVRIO is primarily based on an analysis from subjects followed through Day 29 in the Phase 3 study in non-hospitalized subjects with COVID-19 (MOVe-OUT).
The safety of LAGEVRIO was evaluated based on an analysis of a Phase 3 double-blind trial (MOVe-OUT) in which 1,411 non-hospitalized subjects with COVID-19 were randomized and treated with LAGEVRIO (N=710) or placebo (N=701) for up to 5 days. Adverse events were those reported while subjects were on study intervention or within 14 days of study intervention completion/discontinuation.
Discontinuation of study intervention due to an adverse event occurred in 1% of subjects receiving LAGEVRIO and 3% of subjects receiving placebo. Serious adverse events occurred in 7% of subjects receiving LAGEVRIO and 10% receiving placebo; most serious adverse events were COVID-19 related. Adverse events leading to death occurred in 2 (<1%) subjects receiving LAGEVRIO and 12 (2%) of subjects receiving placebo.
The most common adverse reactions in the LAGEVRIO treatment group in MOVe-OUT are presented in the table below, all of which were Grade 1 (mild) or Grade 2 (moderate).
Adverse Reactions Occurring in Greater Than or Equal to 1% of Subjects Receiving LAGEVRIO in MOVe-OUT 1,b
bFrequencies of adverse reactions are based on all adverse events attributed to study intervention by the investigator.
Selected Grade 3 and 4 laboratory abnormalities in chemistry (alanine aminotransferase, aspartate aminotransferase, creatinine, and lipase) and hematology (hemoglobin, platelets, and leukocytes) parameters all occurred at a rate of less than or equal to 2% and occurred at a similar rate across arms in MOVe-OUT.