Remdesivir
Emergency Use Authorization and Approval
The FDA approved remdesivir (Veklury, Gilead), on 10/22/2020, for the treatment of hospitalized COVID-19 patients that are 12 and up and weigh at least 40 kg (88.2 lbs). The FDA expanded approval for remdesivir, on 4/25/2022, for children 28 days and older, who weigh at least 3 kg (7 lbs), if they are hospitalized or outpatients at high risk for progression to severe COVID-19. The FDA expanded the EUA for remdesivir to include a three-day outpatient course in non-hospitalized patients with mild-to-moderate COVID-19 at high risk to progress to severe disease.
The FDA granted an EUA for the combination of baricitinib (Olumiant. Lilly) plus remdesivir (Veklury, Gilead) to treat hospitalized adults and pediatric patients two years of age or older, with COVID-19 and who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The approval was based on the 29-day, 1,034 patient, Phase III, ACTT 2 trial (NCT04401579), where baricitinib added to remdesivir reduced the time to hospital discharge by one day (7 vs 8 days) compared to remdesivir alone in hospitalized patients with COVID-19. ACTT 2 was sponsored by NIAID. The largest effect was seen in patients requiring supplemental oxygen or high-flow oxygen/non-invasive ventilation.
ICER revised its preliminary pricing review for remdesivir on 6/24/2020. ICER has provided two pricing estimates. One is a cost recovery pricing estimate, based on a review of the cost of producing the final finished product and estimated development costs. ICER estimated a cost recovery price of $1,600 for a 10-day course of treatment. Using a threshold price of $50,000 per incremental quality-adjusted life year (and equal value of a life-year gained) and the benefits seen in the Adaptive COVID-19 Treatment Trial (ACTT), ICER estimated a cost-effective price of $4,580 to 5,080 for a 10-day course of remdesivir. ICER also estimated the effect that dexamethasone would contribute and estimated a lower cost-effectiveness price of $2,520 to $2,800 based on non-peer reviewed data from the RECOVERY trial.
The FDA defines severe COVID-19 as patients with low blood oxygen (SpO2 of 94% or less) that require supplemental oxygen with or without a mechanical ventilator or ECMO. The drug is approved to be administered in hospitalized patients.
In an update, the American College of Physician recommend that remdesivir should not be initiated in hospitalized COVID-19 patients receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO) because the infection has likely progressed to the inflammatory stage of the disease. ACP does recommend consideration of remdesivir for five days in hospitalized patients that do not require ventilation or ECMO. Remdesivir may be given for up to ten days 10 days in patients that progress to mechanical ventilation or ECMO and have already started the drug.
Please see the full prescribing information including administration, dosing and recommendation for monitoring and management of remdesivir patients.
Clinical Experience
Gilead is evaluating remdesivir administered as an inhalation in a Phase I study in healthy volunteers and hopes to initiate a COVID-19 patient trial in August 2020, with this formulation.
To make administration easier, Gilead is developing GS-5245, an oral prodrug for remdesivir
The FDA approved remdesivir (Veklury, Gilead), on 10/22/2020, for the treatment of hospitalized COVID-19 patients that are 12 and up and weigh at least 40 kg (88.2 lbs). The FDA expanded approval for remdesivir, on 4/25/2022, for children 28 days and older, who weigh at least 3 kg (7 lbs), if they are hospitalized or outpatients at high risk for progression to severe COVID-19. The FDA expanded the EUA for remdesivir to include a three-day outpatient course in non-hospitalized patients with mild-to-moderate COVID-19 at high risk to progress to severe disease.
The FDA granted an EUA for the combination of baricitinib (Olumiant. Lilly) plus remdesivir (Veklury, Gilead) to treat hospitalized adults and pediatric patients two years of age or older, with COVID-19 and who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). The approval was based on the 29-day, 1,034 patient, Phase III, ACTT 2 trial (NCT04401579), where baricitinib added to remdesivir reduced the time to hospital discharge by one day (7 vs 8 days) compared to remdesivir alone in hospitalized patients with COVID-19. ACTT 2 was sponsored by NIAID. The largest effect was seen in patients requiring supplemental oxygen or high-flow oxygen/non-invasive ventilation.
ICER revised its preliminary pricing review for remdesivir on 6/24/2020. ICER has provided two pricing estimates. One is a cost recovery pricing estimate, based on a review of the cost of producing the final finished product and estimated development costs. ICER estimated a cost recovery price of $1,600 for a 10-day course of treatment. Using a threshold price of $50,000 per incremental quality-adjusted life year (and equal value of a life-year gained) and the benefits seen in the Adaptive COVID-19 Treatment Trial (ACTT), ICER estimated a cost-effective price of $4,580 to 5,080 for a 10-day course of remdesivir. ICER also estimated the effect that dexamethasone would contribute and estimated a lower cost-effectiveness price of $2,520 to $2,800 based on non-peer reviewed data from the RECOVERY trial.
The FDA defines severe COVID-19 as patients with low blood oxygen (SpO2 of 94% or less) that require supplemental oxygen with or without a mechanical ventilator or ECMO. The drug is approved to be administered in hospitalized patients.
In an update, the American College of Physician recommend that remdesivir should not be initiated in hospitalized COVID-19 patients receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO) because the infection has likely progressed to the inflammatory stage of the disease. ACP does recommend consideration of remdesivir for five days in hospitalized patients that do not require ventilation or ECMO. Remdesivir may be given for up to ten days 10 days in patients that progress to mechanical ventilation or ECMO and have already started the drug.
Please see the full prescribing information including administration, dosing and recommendation for monitoring and management of remdesivir patients.
Clinical Experience
- In a 28-day, 237 patient, Phase III, Chinese trial, treatment with remdesivir for ten days was not associated with a clinical benefit compared to placebo (non-significant 20 days vs 23 days) in hospitalized patients with severe COVID-19 infection (NCT04257656). Due to a decrease in patients with COVID-19 infections in China, enrollment was suspended after 237 patients entered the study instead of the target of 450 patients, which reduced the statistical power from 80% to 58%. The researchers noted they “could not exclude clinically meaningful differences and saw numerical reductions in some clinical parameters". Confounders in this study included 54% of the patients in the remdesivir group receiving the drug more than 10-days after developing symptoms compared to 40% of placebo patients. Almost 30% of remdesivir patients received interferon and/or lopinavir–ritonavir. While use of lopinavir–ritonavir was similar in both groups, 38% of patients received interferon. The placebo group was 65% male compared to 56% in the remdesivir group. These differences could have been due to the final population not reaching the target total.
- Results were published from the first 397 patients enrolled in a 6,000 patient, Phase III trial (NCT04292899), which found no difference in efficacy, measured on a seven-point scale that runs from death to not hospitalized, between a 5-day course of remdesivir and a 10-day course in hospitalized patients with severe COVID-19. The data suggested that earlier treatment was more efficacious than later treatment. An accompanying editorial recommended that 5-day treatment be given priority due to the limited supply of the drug.
- In an 11-day, 584 patient, Phase III, open-label trial (NCT04292730), patients treated with a 5-day course of remdesivir were more likely to have at least a 2-point improvement on a seven-point scale that runs from death to not hospitalized compared to placebo (70% vs 61%) in hospitalized patients with moderate COVID-19. A 10-day course of remdesivir did not differ from placebo (65% vs 61%), although most patients did not receive a full 10-days of treatment. Patients in the standard of care group were more likely to receive lopinavir-ritonavir, corticosteroids, hydroxychloroquine/chloroquine, azithromycin or tocilizumab.
- The ACTT-1 investigators provided a final report on the NIAID sponsored study. In the 29-day, 1,062 patient, Phase III, Adaptive COVID-19 Treatment Trial (ACTT-1) (NCT04280705), patients treated with remdesivir for up to ten days had a median time of recovery (hospital discharge or returning to normal activity level) of 10 days compared to 15 days with placebo in patients with severe COVID-19. However, there was not a significant improvement for patients that required a ventilator or ECMO at study entry. At day 15, there was a significant difference in mortality with remdesivir compared to placebo (6.7% vs 11.9%), but the difference was no longer significant at 29 days (11.4% and 15.2%).
- In the NIAID sponsored 29-day, 1,033 patient, Phase III, ACTT 2 trial (NCT04401579), baricitinib added to remdesivir reduced the time to recovery by one day (7 vs 8 days) compared to remdesivir alone in hospitalized patients with moderate to severe COVID-19. The largest effect was seen in patients receiving high-flow oxygen or non-invasive ventilation (10 vs 18 days)
- In the WHO sponsored, open-label 8,275 patient, Phase III SOLIDARITY trial (NCT04315948), treatment with remdesivir did not improve mortality compared to placebo in the hospitalized patients with COVID-19. There was no statistical difference in mortality in patients who already required ventilation but was lower in patients not on a ventilator (11.9% vs. 13.5%). Among patients not requiring mechanical ventilation at treatment initiation, fewer remdesivir patients progressed to a ventilator than those who received placebo (14.1% vs 15.7%).
- An unpublished and unedited invitro study that tested the antiviral effects of plitidepsin, ralimetinib and remdesivir on early SARS-CoV-2 and the B.1.1.7 variant found similar activity with both viral strains.
- In a retrospective review of 2,483 consecutive patients with severe COVID-19, 342 patients received remdesivir with 184 also receiving corticosteroids. Treatment with remdesivir resulted in a decrease in time to clinical improvement (5 vs 7 days). Mortality had a non-significant decrease (7.7% vs 14%), which was not affected by use of corticosteroids. The patient population was 80% non-white, compared to 30% to 47% in clinical trials.
- In the 28-day, 562 patient, Phase III, PINETREE trial (NCT04501952), 0.7% of patients treated with a 3-day course of remdesivir were hospitalized or died compared to 5.3% with placebo in nonhospitalized patients with at least one risk factor to progress to severe disease. Enrollment was stopped early in April 2021 prior to fulfilling the 1,264 patient enrollment due to a change in epidemiology and adoption of additional treatment options at the time.
- In the 15-day, 857 patient, Phase III, DisCoVeRy trial (NCT04315948), adding remdesivir to standard-of care did not improve clinical status (WHO seven-point ordinal scale) compared to standard-of-care alone in European hospitalized patients with COVID-19 for more than 7 days, who were receiving supplemental oxygen.
- In a retrospective analysis of outcomes from 10,445 COVID-19 patients in Hong Kong, adding dexamethasone after starting remdesivir or giving the drugs simultaneously reduced hospital stay and hospital mortality compared to adding remdesivir two days after dexamethasone or not using remdesivir at all.
Gilead is evaluating remdesivir administered as an inhalation in a Phase I study in healthy volunteers and hopes to initiate a COVID-19 patient trial in August 2020, with this formulation.
To make administration easier, Gilead is developing GS-5245, an oral prodrug for remdesivir
Services |
Company |
|