Veklury® (remdesivir)

Use in Immunocompromised Patients

This document is in response to your request for information regarding the use of Veklury® (remdesivir [RDV]) in immunocompromised patients. This response was developed according to principles of evidence-based medicine and contains data from phase 3 clinical studies, real-world data, and retrospective studies (N≥200).

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

Clinical Data: VKY Use in Immunocompromised Patients

Currently, there are no clinical trial data available on the use of RDV in immunocompromised patients. Although some clinical trials, including ACTT-1 and PINETREE, with RDV included some immunocompromised participants, efficacy and safety results were not reported for these participants.1,2

Retrospective Data: VKY Use in Immunocompromised Patients

In a retrospective, comparative effectiveness cohort analysis of immunocompromised patients (included patients with cancer, transplant, hematologic malignancies, PID, SCID, immunosuppressive medications, asplenia, bone marrow failure/aplastic anemia, HIV, or toxic effects of antineoplastics) from the PINC AI Healthcare Database who were hospitalized with COVID-19 from December 1, 2021, to April 30, 2023 (Omicron period), RDV was associated with a lower risk of mortality compared with those without RDV
(Figure 1). After adjusting for clinical covariates, RDV treatment was associated with lower mortality at Day 14 overall (aHR: 0.73; 95% CI: 0.65–0.82; P<0.0001) and at Day 28 overall (aHR: 0.75; 95% CI: 0.68–0.83; P<0.0001).3

Treatment outcomes with RDV have been reported in a retrospective, single-center cohort study and in a retrospective analysis of registry data in patients with various immunocompromised conditions, including SOT4 and various other PIDs or SIDs.5

Clinical Data: VKY Use in Immunocompromised Patients

Currently, there are no clinical trial data available evaluating the use of RDV in immunocompromised patients.

NIAID-Sponsored Study: ACTT-1

A phase 3, randomized, adaptive, double-blind, placebo-controlled, multicenter study evaluated the safety and efficacy of RDV (n=541) vs placebo (n=521) in hospitalized adult participants diagnosed with COVID-19 with evidence of lower respiratory tract infection.6 Immune system disorder (definition not provided) was noted as a comorbidity in 32 (6%) and 41 (8%) participants in the RDV and placebo groups, respectively. Efficacy and safety results were not provided for this subset of participants.1

RDV IV Outpatient Study: PINETREE

A phase 3, randomized, double-blind, placebo-controlled, multicenter study evaluated the safety and efficacy of a 3-day course of RDV (n=279) or placebo (n=283) administered IV in an outpatient setting in nonhospitalized participants with baseline characteristics that increased their risk for COVID-19 disease progression. Risk factors for progression included immunocompromised status, defined as having undergone an SOT, a blood transplant or bone marrow transplant; immune deficiencies; HIV with a low CD4 cell count or not currently receiving HIV treatment; long-term use of corticosteroids; or use of immune‑weakening medications.2,7

Overall, 14 participants (5%) in the RDV group and 9 participants (3.2%) in the placebo group were immunocompromised; 12 (4.3%) and 18 (6.4%) participants in the RDV and placebo groups, respectively, had cancer.2 Efficacy and safety results were not provided for these participants.

Retrospective Data: VKY Use in Immunocompromised Patients

Retrospective, Comparative Effectiveness Cohort Study

Study design and demographics3

A retrospective, comparative effectiveness cohort study evaluated all-cause in-hospital mortality at Days 14 and 28 among immunocompromised patients with a primary discharge diagnosis of COVID-19 (present on admission) during the Omicron period (December 2021–‍April 2023) who were treated with RDV (initiated within 2 days of admission) and those who were not treated with RDV during their hospitalization. Immunocompromised states included cancer, transplant, hematologic malignancies, PID, SCID, immunosuppressive medications, asplenia, bone marrow failure/aplastic anemia, HIV, or toxic effects of antineoplastics. Data were obtained from the US-based PINC AI Healthcare Database (formerly known as the Premier Healthcare Database), and patients were PS‑matched (1:1 matching with replacement, each PS-matched cohort, n=10,687) by baseline supplemental O2 requirement, which was determined within the first 2 days of hospitalization. In the overall matched cohort at baseline, 74% of patients were ≥65 years old, and 51% had supplemental O2 needs.

Results

In the PS-matched cohort, patients treated with RDV had a lower unadjusted 14- and 28-day mortality rate overall. A lower unadjusted mortality rate was observed among patients with and without supplemental O2 needs, compared with the no RDV cohort (Table 1).3

Table 1. Unadjusted Analysis of PS-Matched Cohort –
Mortality Rates at Days 14 and 28 Overall and by Baseline O2 Requirements3

In an adjusted analysis (for age, admission month, intensive care unit vs general ward, and baseline treatments), RDV treatment was associated with lower mortality at Day 14 overall (aHR: 0.73; 95% CI: 0.65–0.82; P<0.0001) and at Day 28 overall (aHR: 0.75; 95% CI: 0.68–‍0.83; P<0.0001), compared with patients who did not receive RDV. Lower 14- and 28‑day mortality risks were also observed in subgroups of patients with no supplemental O2 needs and with any supplemental O2 requirements (Figure 1).3

Figure 1. Adjusted Cox Proportional Hazards Model of PS-Matched Cohort –
Mortality at Days 14 and 28 Overall and by Baseline O2 Requirements3

Data from pre-Delta (December 2020–April 2021), Delta (May–November 2021), and Omicron (December 2021–April 2022) VOCs have been previously published; a significantly lower mortality risk was associated with RDV treatment over no RDV treatment and were observed across each VOC period. In subgroup analyses according to baseline O2 requirement, numerically lower mortality rates with RDV were observed, compared with the no RDV cohort.8

Retrospective, Single-Center Study of Transplant Recipients in Iran4

The retrospective, single-center study in Iran evaluated outcomes in 245 transplant recipients (kidney, liver, simultaneous pancreas-kidney, isolated bowel, and multivisceral transplants) who were diagnosed with COVID-19 from March 2020 to May 2021. Patients with moderate to severe COVID-19 were eligible to receive RDV for up to 5 days (n=102).

Relative to those who did not receive RDV, RDV-treated patients had a shorter length of stay in the intensive care unit (mean [SEM]: 24.31 days [12.41] vs 18.91 days [10]; P=0.03) and in the hospital (mean [SEM], 34.45 days [13.76] vs 27 days [11.65]; P<0.001). Of the 102 participants who received RDV, 89 did not require MV, and 92 survived. In a multivariate logistic regression analysis, treatment with RDV was significantly associated with survival (OR: 2.2 [95% CI: 0.07–0.81]; P=0.02) but was not significantly associated with the initiation of MV (OR: 1.7 [95% CI: 0.85–4.4; P=0.11). The incidence of clinical complications was not significantly different between patients who received RDV and those who received other COVID-19–directed treatments (all P>0.05), and the following complications were observed in RDV-treated patients: reduced GFR, n=12; elevated liver enzymes, n=11; gastrointestinal complications, n=9; bacterial superinfection, n=7; neutropenia or thrombocytopenia, n=4.

UK PIN: COVID-19-Related Morbidity and Mortality in Patients With PID or SID5

A retrospective analysis of morbidity and mortality data from the UK PIN registry included 310 patients with PID (n=218) and SID (n=92) who were diagnosed with COVID-19 between March 2020 and July 2021. Data were analyzed according to the following three groups: patients with CVID; patients with PID who were receiving Ig replacement (also included patients with CVID but excluded 6 patients who underwent allogeneic HSCT or gene therapy); and patients with SID.

Of the 144 patients who required hospital admission, 89 survived (61.8%), and 33 (22.9%) received COVID-19–directed treatment. Of those 33 patients, 26 received RDV, 20 received dexamethasone, and 10 received antibody-based therapies (eg, casirivimab/imdevimab or convalescent plasma) alone or with other agents; the survival rate of patients who received RDV-based treatment was 84.6% (Table 2).

Table 2. UK PIN: RDV-Based Treatment Recipient Patient Characteristics and Outcomes5

aMedians are reported for treatment groups with >1 patient, and age groups are reported for treatment groups with 1 patient.

References

1. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 — Final Report [Supplementary Appendix]. N Engl J Med. 2020.

2. Gottlieb RL, Vaca CE, Paredes R, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Eng J Med. 2022;386(4):305-315.

3. Mozaffari E, Chandak A, Gottlieb RL, et al. Remdesivir Reduces Mortality in Immunocompromised Patients Hospitalised for COVID-19 During Omicron [Poster 664]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 3-6, 2024; Denver, CO.

4. Shafiekhani M, Shahabinezhad F, Niknam T, et al. Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand? Virology journal. 2021;18(1):228.

5. Shields AM, Anantharachagan A, Arumugakani G, et al. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK [Advanced Access Publication]. Clinical and experimental immunology. 2022:1-12.

6. Beigel JH, Tomashek KM, Dodd LE, et al. Remdesivir for the Treatment of Covid-19 — Final Report. N Engl J Med. 2020;383(19):1813-1826.

7. Gottlieb RL, Vaca CE, Paredes R, et al. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients [Protocol]. N Eng J Med. 2021.

8. Mozaffari E, Chandak A, Gottlieb RL, et al. Remdesivir reduced mortality in immunocompromised patients hospitalized for COVID-19 across variant waves: Findings from routine clinical practice. Clin Infect Dis. 2023.

Abbreviations

ACTT-1=Adaptive COVID19 Treatment Trial-1
aHR=adjusted hazard ratio
CVID=common variable immunodeficiency
HSCT=hematopoietic stem cell transplantation
MV=mechanical ventilation
NIAID=National Institute of Allergy and Infectious Diseases
O2=oxygen
OR=odds ratio
PID=primary immunodeficiency
PINC AI=Premier Inc. Artificial Intelligence
PS=propensity score
RDV=remdesivir
SCID=severe combined immunodeficiency
SEM=standard error of the mean
SID=secondary immunodeficiency
SOT=solid organ transplantation
UK PIN=United Kingdom Primary Immunodeficiency Network
VOC=variants of concern

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

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