Regulatory Decision Summary for Veklury
Antivirals for systemic use
Type of Submission:
Supplement to a New Drug Submission
Authorized; issued a Notice of Compliance in accordance with the Food and Drug Regulations
What was the purpose of this submission?
The purpose of this Supplemental New Drug Submission (SNDS) was to expand the indication for Veklury (remdesivir) in the treatment of coronavirus disease 2019 (COVID-19) to pediatric patients at least 4 weeks of age and weighing at least 3 kg to less than 40 kg with pneumonia requiring supplemental oxygen (hospitalized pediatric patients) and pediatric patients weighing at least 40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death (non-hospitalized pediatric patients). Upon review, this expansion of the indication was considered acceptable.
Why was the decision issued?
The indication for Veklury in the treatment of coronavirus disease 2019 (COVID-19) in pediatric patients at least 4 weeks of age and weighing at least 3 kg to less than 40 kg with pneumonia requiring supplemental oxygen (hospitalized pediatric patients) and pediatric patients weighing at least 40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death (non-hospitalized pediatric patients), was supported by pharmacokinetic, safety and efficacy data from clinical studies GS-US-540-5823 and GS-US-540-912 (reviewed by Health Canada previously in a Supplemental New Drug Submission [SNDS] Control Number 250151), and also by the population pharmacokinetic analysis.
Study GS-US-540-5823 is an ongoing single-arm, open-label Phase 2/3 trial to evaluate the pharmacokinetics and safety of Veklury administered for up to 10 days. An interim report for 53 pediatric patients in 5 cohorts was submitted by the sponsor in this SNDS that included: patients ≥12 years and weighing ≥40 kg (n = 12); patients <12 years and weighing ≥40 kg (n = 5); patients ≥28 days and weighing ≥20 to <40 kg (n = 12); patients ≥28 days and weighing ≥12 to <20 kg (n = 12); and patients ≥28 days and weighing ≥3 to <12 kg (n = 12). Patients weighing ≥40 kg received 200 mg of Veklury on Day 1 followed by Veklury 100 mg once daily on subsequent days; patients weighing ≥3 kg to <40 kg received Veklury 5 mg/kg on Day 1 followed by Veklury 2.5 mg/kg once daily on subsequent days. At baseline, median age was 7 years (Q1, Q3: 2 years, 12 years); 57% of patients were female, 70% were White, 30% were Black, and 44% were Hispanic or Latino; and mean weight was 38 kg (range: 4 to 192 kg). A total of 12 patients (23%) were on invasive mechanical ventilation; 18 (34%) were on non-invasive ventilation or high-flow oxygen; 10 (19%) were on low-flow oxygen; and 13 (25%) were on room air. The overall median (Q1, Q3) duration of symptoms and hospitalization prior to first dose of Veklury was 5 (3, 7) days and 1 (1, 3) day, respectively.
Population pharmacokinetic models for remdesivir and its circulating metabolites (GS-704277 and GS‑441524), developed using pooled data from studies in healthy subjects and in adult and pediatric patients with COVID-19, were used to predict pharmacokinetic exposures in hospitalized pediatric patients aged ≥28 days to <18 years and weighing ≥3 kg in study GS-US-540-5823. Mean exposures (AUCtau and Cmax) of remdesivir, GS-704277, and GS-441524 predicted for these patients at the doses administered were higher as compared to those in adult patients with COVID-19; however, this increased exposure was not considered clinically significant.
The adverse reactions observed in study GS-US-540-5823 were consistent with those observed in clinical trials of Veklury in adults. Adverse reactions (all grades) were reported in 8 (15%) subjects. The most common adverse reaction occurring in at least 5% of patients was alanine aminotransaminase increased (6%). No subjects experienced serious adverse reactions. Two (4%) subjects permanently discontinued treatment due to adverse reactions.
Treatment with Veklury in study GS-US-540-5823 for up to 10 days resulted in an overall median (Q1, Q3) change from baseline in clinical status (assessed on a 7-point ordinal scale ranging from death [score of 1] to ventilatory support and decreasing levels of oxygen to hospital discharge [score of 7]) of +2.0 (1.0, 4.0) points on Day 10. Recovery (defined as an improvement from a baseline clinical status score of 2 through 5 to a score of 6 or 7, or an improvement from a baseline score of 6 to a score of 7) was reported for 62% of patients on Day 10; median (Q1, Q3) time to recovery was 7 (5, 16) days. Overall, 60% of patients were discharged by Day 10. Three patients died during the study but none of these deaths was considered to be related to treatment with Veklury.
Study GS-US-540-9012 was a randomized, double-blind, placebo-controlled, Phase 3 clinical trial that evaluated Veklury 200 mg once daily for 1 day followed by Veklury 100 mg once daily for 2 days (for a total of 3 days of intravenously administered therapy) in 562 adult and pediatric patients (12 years of age and older and weighing at least 40 kg) with confirmed SARS-CoV-2 infection and at least one risk factor for progression to hospitalization. The study included 8 adolescent patients of whom 3 patients received Veklury. None of these patients had COVID-19-related hospitalization, COVID-19-related medically attended visit, or died due to any cause by Day 28. No adverse events were reported in adolescent patients that received Veklury.
In summary, based on the review of submitted evidence, it is considered that the benefit-harm-uncertainty profile of Veklury is favorable in the treatment of COVID-19 in pediatric patients at least 4 weeks of age and weighing at least 3 kg to less than 40 kg with pneumonia requiring supplemental oxygen and pediatric patients weighing at least 40 kg who are at high risk for progression to severe COVID-19, including hospitalization or death.
For further details about Veklury, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.
Date of Decision:
Manufacturer / Sponsor:
Drug Identification Number(s) Issued:
Available by prescription only