CLINICAL TRIAL RESULTS

Remdesivir is an antiviral drug with available data from three randomized clinical trials in patients with COVID-19.

NIAID ACTT-1 Study in Subjects with Mild/Moderate and Severe COVID-19

A randomized, double-blind, placebo-controlled clinical trial (ACTT-1, NCT04280705) of hospitalized adult subjects with confirmed SARS-CoV-2 infection and mild, moderate, or severe COVID-19 compared treatment with remdesivir for 10 days (n=541) with placebo (n=521 ). Mild/moderate disease was defined as SpO2 >94% and respiratory rate <24 breaths/minute without supplemental oxygen; severe disease was defined as an SpO2 ≤94% on room air, a respiratory rate ≥24 breaths/minute, an oxygen requirement, or a requirement for mechanical ventilation. Subjects had to have at least one of the following to be enrolled in the trial: radiographic infiltrates by imaging, SpO2 ≤94% on room air, a requirement for supplemental oxygen, or a requirement for mechanical ventilation. Subjects treated with remdesivir received 200 mg on Day 1 and 100 mg once daily on subsequent days, for 10 days of treatment via intravenous infusion. Treatment with remdesivir was stopped in subjects who were discharged from the hospital prior to the completion of 10 days of treatment.

At baseline, mean age was 59 years (with 36% of subjects aged 65 or older); 64% of subjects were male, 53% were White, 21% were Black, and 13% were Asian; 24% were Hispanic or Latino; 105 subjects had mild/moderate disease (10% in both treatment groups); 957 subjects had severe disease (90% in both treatment groups).A total of 285 subjects (27%) (n=131 received remdesivir) were on invasive mechanical ventilation or ECMO. The most common comorbidities were hypertension (51%), obesity (45%), and type 2 diabetes mellitus (31%); the distribution of comorbidities was similar between the two treatment groups.

The primary clinical endpoint was time to recovery within 29 days after randomization. Recovery was defined as discharged from the hospital without limitations on activities, discharged from the hospital with limitations on activities and/or requiring home oxygen, or hospitalized but not requiring supplemental oxygen and no longer requiring ongoing medical care. The median time to recovery was 10 days in the remdesivir group compared to 15 days in the placebo group (recovery rate ratio 1.29 [95% Cl 1.12 to 1.49], p<0.001). Among subjects with mild/moderate disease at enrollment (n=105), the median time to recovery was 5 days in both the remdesivir and placebo groups (recovery rate ratio 1.22 [95% Cl 0.82 to 1.81]). Among subjects with severe disease at enrollment (n=957), the median time to recovery was 11 days in the remdesivir group compared to 18 days in the placebo group (recovery rate ratio 1.31 [95% Cl 1.12 to 1.521).

A key secondary endpoint was clinical status on Day 15 assessed on an 8-point ordinal scale consisting of the following categories :

1. not hospitalized, no limitations on activities;
2. not hospitalized, limitation on activities and/or requiring home oxygen;
3. hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
4. hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
5. hospitalized, requiring supplemental oxygen;
6. hospitalized, on noninvasive ventilation or high-flow oxygen devices;
7. hospitalized, on invasive mechanical ventilation or ECMO; and
8. death.

Overall, the odds of improvement in the ordinal scale were higher in the remdesivir group at Day 15 when compared to the placebo group (odds ratio 1.54 [95% Cl 1.25 to 1.91 ]).

Overall, 29-day mortality was 11% for the remdesivir group vs 15% for the placebo group (hazard ratio 0.73 [95% Cl 0.52 to 1.03]).

Study GS-US-540-5773 In Subjects with Severe COVID-19

A randomized, open-label multi-center clinical trial (Study 5773, NCT04292899) in adult subjects with confirmed SARS-CoV-2 infection, an SpO2 of <94% on room air, and radiological evidence of pneumonia compared 200 subjects who received remdesivir for 5 days with 197 subjects who received remdesivir for 10 days. Treatment with remdesivir was stopped in subjects who were discharged from the hospital prior to completion of their protocol-defined duration of treatment. Subjects on mechanical ventilation at screening were excluded. All subjects received 200 mg of remdesivir on Day 1 and 100 mg once daily on subsequent days via intravenous infusion, plus standard of care. At baseline, the median age of subjects was 61 years (range, 20 to 98 years); 64% were male, 75% were White, 12% were Black, and 12% were Asian; 22% were Hispanic or Latino. More subjects in the 10-day group than the 5-day group required invasive mechanical ventilation or ECMO (5% vs 2%), or high-flow oxygen support (30% vs 25%) at baseline. Median duration of symptoms and hospitalization prior to first dose of remdesivir were similar across treatment groups. The primary endpoint was clinical status on Day 14 assessed on a 7-point ordinal scale consisting of the following categories: 1. death; 2. hospitalized, receiving invasive mechanical ventilation or ECMO; 3. hospitalized, receiving noninvasive ventilation or high-flow oxygen devices; 4. hospitalized, requiring low-flow supplemental oxygen; 5. hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to COVID-19); 6. hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and 7. not hospitalized. 34 Overall, after adjusting for betweengroup ditferences at baseline, subjects receiving a 5-day course of remdesivir had similar clinical status at Day 14 as those receiving a 10-day course (odds ratio for improvement 0. 75 [95% Cl 0.51 to 1.12]). There were no statistically signmcant ditferences in recovery rates or mortality rates in the 5-day and 10-day groups once adjusted for between-group differences at baseline. All-cause mortality at Day 28 was 12% vs 14% in the 5- and 10-day treatment groups, respectively.

Study GS-US-540-5774 in Subjects with Moderate COVID-19

A randomized, open-label multi-center clinical trial (study 5774, NCT04292730) of hospitalized adult subjects with confirmed SARS-CoV-2 infection, SpO2 >94% and radiological evidence of pneumonia compared treatment with remdesivir for 5 days (n=191) and treatment with remdesivir for 10 days (n= 193) with standard of care (n=200). Treatment with remdesivir was stopped in subjects who were discharged from the hospital prior to completion of their protocol-defined duration of treatment. Subjects treated with remdesivir received 200 mg on Day 1 and 100 mg once daily on subsequent days via intravenous infusion. At baseline, the median age of subjects was 57 years (range, 12 to 95 years); 61% were male, 61% were White, 19% were Black, and 19% were Asian; 18% were Hispanic or Latino. Baseline clinical status, oxygen support status, and median duration of symptoms and hospitalization prior to first dose of remdesivir were similar across treatment groups. The primary endpoint was clinical status on Day 11 assessed on a 7-point ordinal scale consisting of the following categories: 1. death; 2. hospitalized, receiving invasive mechanical ventilation or ECMO; 3. hospitalized, receiving noninvasive ventilation or high-flow oxygen devices; 4. hospitalized, requiring low-flow supplemental oxygen; 5. hospitalized, not requiring supplemental oxygen but receiving ongoing medical care (related or not related to COVID-19); 6. hospitalized, requiring neither supplemental oxygen nor ongoing medical care (other than that specified in the protocol for remdesivir administration); and 7. not hospitalized. Overall, the odds of improvement in the ordinal scale were higher in the 5-day remdesivir group at Day 11 when compared to those receiving only standard of care (odds ratio 1.65 195% Cl 1.09 to 2.48], p=0.017). The odds of improvement in clinical status with the 10 days treatment group when compared to those receiving only standard of care were not statistically significant (odds ratio 1.31 [95% Cl 0.88 to 1.95]). All-cause mortality at Day 28 was ≤2% in all treatment groups.