Veklury® (remdesivir)

SIMPLE Study in Patients With Moderate COVID-19

This document is in response to your request for information on the SIMPLE study, which evaluated the use of Veklury® (remdesivir [RDV]) in hospitalized participants with moderate COVID-19.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at: www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.

Summary

SIMPLE Study: RDV in Moderate COVID-19

A phase 3, randomized, open-label study compared the outcomes of 5 or 10 days of RDV treatment with SOC in hospitalized participants with moderate COVID-19.1,2

• Participants in the 5‑day RDV treatment group had 65% higher odds of experiencing clinical improvement than those in the SOC treatment group at Day 11 (OR: 1.65; 95% CI: 1.09 to 2.48; P=0.02).1
• The difference in clinical status distribution between the 10‑day RDV and SOC groups was not statistically significant at Day 11 (P=0.18).1
• Rates of SAEs were numerically lower with RDV than with SOC. The most common AEs were nausea and diarrhea. No significant differences in the changes in CrCl, ALT levels, or AST levels over time were observed between participants who received RDV and those who received SOC.1

SIMPLE Study: RDV in Moderate COVID-19

Study Design

A phase 3, randomized, two-part (Parts A and B), open-label study evaluated the efficacy of two RDV regimens compared with SOC in participants with moderate COVID-19. Data from participants in Part A, conducted between March 15 and April 18, 2020, are available. The primary efficacy endpoint was the distribution of clinical status scores on a 7-point ordinal scale on Day 11 (each RDV group was compared with the SOC group using a 2‑sided test [α=0.25; Bonferroni]).1,2 The secondary endpoint was the proportion of participants with AEs throughout the study.1

Part A consisted of 596 participants who were randomly assigned to receive SOC therapy according to local guidelines either alone or with a 5- or 10-day course of RDV (loading dose of RDV 200 mg IV on Day 1, followed by RDV 100 mg/day IV for either 4 days or for 9 days). RDV was infused over 30 to 60 minutes.1

Figure 1. SIMPLE Study in Moderate COVID-19: Study Design1,3

Abbreviations: PCR=polymerase chain reaction; SpO2=serum pressure O2.

aAdults ≥18 years or adolescents between 12 and 18 years (weighing ≥40 kg) were included.

bSOC per local written policies or guidelines.

cThe primary efficacy population was composed of participants from Part A. Clinical status was assessed with a 7-point ordinal scale that includes the following categories: 1) death; 2) hospitalized and requires invasive mechanical ventilation or extracorporeal membrane oxygenation; 3) hospitalized and requires NIV or high-flow O2 devices; 4) hospitalized and requires low-flow supplemental O2; 5) hospitalized and does not require supplemental O2 but requires ongoing medical care (COVID-19–related or otherwise); 6) hospitalized but does not require supplemental O2 or ongoing medical care; 7) not hospitalized.

dIn Part B, treatment may be reduced to a total of 5 days following an analysis of the data from Part A.

Note: A total of 600 participants (200 per group) was calculated in order to provide >85% power to detect an OR of 1.8 for each RDV group compared to the SOC group. Of the 596 participants who underwent randomization, 584 participants began the study.

Baseline Demographics and Participant Disposition1

Baseline characteristics were balanced among the three groups; however, more participants in the SOC group than in either RDV group received concomitant medications to treat COVID-19.

Table 1. SIMPLE Study in Moderate COVID-19: Select Baseline Demographics and Disease Characteristics1

aOther included American Indian or Alaska Native, Native Hawaiian or Pacific Islander, Arab, unknown, and not specified.

bDespite not requiring medical care, some participants stayed in the hospital for quarantine or social issues.

cConcomitant medications included those taken between Day 1 and the last day of RDV or after Day 1 in the SOC group.

Seventy-six percent of participants (145/191) in the 5-day group received all 5 days of RDV treatment (median [range] doses: 5 [1–5]), and 38% of participants (73/193) in the 10-day group received all 10 days of RDV treatment (median [range] doses: 6 [1–10]). The most common reason for RDV discontinuation was hospital discharge (5-day group: 18%; 10-day group: 51%). Thirty-seven participants did not die, were not yet discharged, or did not have clinical status available for Day 11; therefore, the last available clinical status data were used for these participants.

Efficacy1

Participants who received 5 days of RDV had 65% higher odds of having clinical improvement than those in the SOC treatment group at Day 11 (OR: 1.65; 95% CI: 1.09–‍2.48; P=0.02). For participants in the 10-day RDV group, the clinical status distribution was not significantly different compared with the SOC group (P=0.18).

Table 2. SIMPLE Study in Moderate COVID-19: Efficacy Results1,4

The rates of all-cause mortality at Day 28 were not significantly different between the SOC group (2%; 95% CI: 0.1%, 4.1%) and the 5‑day RDV group (1%; 95% CI: 0%, 2.6%; P=0.43) and the 10-day RDV group (2%; 95% CI: 0%, 3.6%; P=0.72).1

Safety

There was a significant difference in rates of AEs observed between the 10-day RDV group and the SOC group (Table 3). Through Day 28, deaths occurred in participants who were ≥64 years of age and were unrelated to RDV treatment (deaths: 5-day RDV, 2 [1%]; 10-day RDV, 3 [2%]; and SOC, 4 [2%]).1

No significant differences in the changes in CrCl, ALT levels, or AST levels over time were observed between participants who received RDV and those who received SOC. One renal‑related SAE of acute kidney injury occurred in the SOC group, and no renal‑related SAEs occurred in either RDV treatment group. None of the deaths were deemed to be treatment related.4

Table 3. SIMPLE Study in Moderate COVID-19: Safety Results1,4

aTwo participants died: 1 death was due to respiratory failure and 1 was due to acute respiratory distress syndrome with worsening lung compliance. Each participant was on room air at baseline.

bThree participants died: 1 death was due to COVID-19 pneumonia, bloodstream infection, and ascending thoracic aortic aneurysm; 1 was due to acute hypoxic respiratory failure; and 1 was due to complete heart block. Each participant was on room air at baseline.

cFour participants died: 3 deaths were due to COVID-19; 1 was due to cardiac arrest (the participant was on bi‑level positive airway pressure and likely hypoxic). Each participant required low-flow O2 at baseline.

Table 4. SIMPLE Study in Moderate COVID-19: Select Laboratory Abnormalities1,4

aGrade 3 CrCl decrease was defined as a CrCl of 30 to <60 mL/min or a decrease of 30% to <50% from baseline.

bGrade 4 CrCl decrease was defined as a CrCl <30 mL/min, decrease of ≥50% from baseline, or need for dialysis.

References

1. Spinner CD, Gottlieb RL, Criner GJ, et al. Effect of Remdesivir vs Standard Care on Clinical Status at 11 Days in Patients With Moderate COVID-19: A Randomized Clinical Trial. JAMA. 2020;324(11):1048-1057. https://jamanetwork.com/journals/jama/fullarticle/2769871

2. ClinicalTrials.gov. Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants With Moderate Coronavirus Disease (COVID-19) Compared to Standard of Care Treatment. ClinicalTrials.gov Identifier: NCT04292730. Last Updated: 26 January, 2021. 2020.

3. Gilead Sciences Inc. Clinical Study Protocol. A Phase 3 Randomized Study to Evaluate the Safety and Antiviral Activity of Remdesivir (GS-5734™) in Participants with Moderate COVID-19 Compared to Standard of Care Treatment. Protocol ID: GS-US-540-5775. 2020.

4. Criner G, Ahn MY, Huhn G, et al. Safety of Remdesivir vs Standard of Care in Patients With Moderate COVID-19 [Poster 561]. Paper presented at: IDWeek Virtual; 21-25 October, 2020.

Abbreviations

AE=adverse event
NIV=non-invasive ventilation
O2=oxygen
OR=odds ratio
RDV=remdesivir

SAE=serious adverse event
SOC=standard of care
ULN=upper limit of normal
 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Veklury US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.

Follow-Up

For any additional questions, please contact Gilead Medical Information at:

☎ 1‐866‐MEDI‐GSI (1‐866‐633‐4474) or   www.askgileadmedical.com

Adverse Event Reporting

Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

Data Privacy

The Medical Information service at Gilead Sciences may collect, store, and use your personal information to provide a response to your medical request. We may share your information with other Gilead Sciences colleagues to ensure that your request is addressed appropriately. If you report an adverse event or concern about the quality of a Gilead or Kite product, we will need to use the information you have given us in order to meet our regulatory requirements in relation to the safety of our medicines.

It may be necessary for us to share your information with Gilead’s affiliates, business partners, service providers, and regulatory authorities located in countries besides your own. Gilead Sciences has implemented measures to protect the personal information you provide. Please see the Gilead Privacy Statement (www.gilead.com/privacy-statements) for more information about how Gilead handles your personal information and your rights. If you have any further questions about the use of your personal information, please contact privacy@gilead.com.

VEKLURY, GILEAD, and the GILEAD logo are registered trademarks of Gilead Sciences, Inc., or its related companies.
© 2024 Gilead Sciences, Inc.