dm+d

38377611000001105

Refrigerated Storage

RemdesivirGilead Sciences Ltd

Gilead Sciences Ltd
Remdesivir
Solution for infusion (concentrate), 100mg/20mL

In the event of an inadvertent temperature excursion the following data may be used:

The manufacturer’s SPC states that sealed vials of remdesivir can be stored at temperatures up to 25°C for up to 12 hours prior to dilution.

However, they also hold data  from in-house stability studies which show that sealed remdesivir vials remain stable for use up to 1 month when stored at 25°C, for up to 4 days when stored at 40°C, and for up to 48 months when stored at -20°C

In the event of a temperature excursion above 8°C,  pharmacy staff are recommended to label the affected remdesivir stock (carton and vials) with an amended expiry date of 28 days from the date when the excursion was detected, before returning it to the fridge and taking steps to make sure it is used before stock with the manufacturer’s original expiry date. If the affected product is unlikely to be used within one month, they should contact their Regional QA Pharmacist with details of the excursion for specialist advice, or their Regional Pharmacy Procurement Specialist to try to arrange transfer to another Trust able to use it within that time.

Yes - as per the information stated above.

During the COVID emergency it is especially important to conserve medicine stocks and to minimise avoidable waste. If ANY critical medicines are subject to temperature excursions during this time and your pharmacy team are in any doubt about whether or not it is safe to use them, you are strongly advised to contact your Regional QA Pharmacist to agree the most appropriate course of action.

24 September 2020
London MI Service

Lactation Safety Information

No published evidence of safety
Minimal absorption anticipated from infants GI tract although long half-life increases risk of accumulation in breastfed infants
Monitor infant for diarrhoea, rash and signs of liver and renal impairment
RCOG and PHE state that breastfeeding can continue during Covid-19 infection
2 July 2020

New Medicines

VekluryCoronavirus disease 2019 (COVID-19)

Information

Veklury
New molecular entity
Gilead Sciences
Gilead Sciences

Development and Regulatory status

Launched
Launched
Pre-registration (Filed)
August 2020
Dec 20The EMA CHMP has recommended a change to the terms of the conditional marketing authorisation, amending the indication. The amended indication is "for the treatment of coronavirus disease 2019 (COVID-19) in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with pneumonia requiring supplemental oxygen (low- or high-flow oxygen or other non-invasive ventilation at start of treatment)" [33].
Aug 20Gilead has submitted NDA for use of remdesivir in covid-19 to US FDA. This is the final tier of the rolling NDA submission that was initiated on April 8, 2020 [28].
Aug 20Is available in the UK for hospital-use only. NHS list price 100mg/20ml concentrate for solution for infusion vials/100mg powder for concentrate for solution for infusion vials: £340/vial [30].
Jul 20NHS England publishes an interim clinical commissioning policy for remdesivir [29].
Jul 20European Commission grants conditional marketing authorisation to remdesivir (Veklury) for treatment of COVID-19. The license is for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen and follows the CHMP recommendation from 25 June 2020 [27].
Jun 20Recommended for conditional EU approval by CHMP - the full indication is "for the treatment of coronavirus disease 2019 (COVID-19) in adults and adolescents (aged 12 years and older with body weight at least 40 kg) with pneumonia requiring supplemental oxygen (see section 5.1)". Conditional approval is granted to a medicinal product that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorisation holder is likely to provide comprehensive clinical data at a later stage [26].
Jun 20EMA press release announces receipt of an application for conditional marketing authorisation (CMA) of remdesivir for the treatment of COVID-19. The agency has formally started its evaluation. Assessment of the benefits and risks of remdesivir is being performed under a reduced timeline and an opinion could be issued within weeks. This short timeframe is possible because some data have already been assessed during the rolling review, which started Apr 20 and concluded May 20 [24].
May 20MHRA grants EAMS status to Gilead Sciences Ltd for remdesivir in the treatment of patients hospitalised with suspected or laboratory-confirmed SARS-CoV-2 infection who meet the clinical criteria [20].
May 20Gilead signed nonexclusive licensing agreements with five generic drug makers operating in India and Pakistan to produce COVID-19 therapy remdesivir for 127 countries [20].
May 20FDA has given emergency use authorization to remdesivir for the treatment of hospitalized 2019 coronavirus disease (COVID-19) patients [19].
Apr 20PIII trials start [10].
Apr 20EMA provides recommendations on compassionate use of remdesivir for COVID-19 in the EU [9].
Feb 20The assistant director-general of the World Health Organization (WHO) has announced at a press conference in Beijing that remdesivir is the only drug currently showing efficacy in patients with the novel Coronavirus infection (now renamed as Covid-19) and anticipates results from the 2 trials underway in China in April 2020 [6].
Feb 20The Wuhan Institute of Virology of the China Academy of Sciences announced their application to patent the use of remdesivir to treat the 2019-novel coronavirus. The application was submitted jointly with the Military Medicine Institute of the People’s Liberation Army Academy of Military Science. Scientists from both institutes said in a paper published in Nature’s Cell Research that they found both remdesivir and the antimalarial, chloroquine, to be effective in inhibiting the coronavirus. The application has drawn controversy since Gilead has patents on the drug for all of its uses, including coronavirus [3].

Category

A small molecule and monophosphoramidate prodrug of adenine nucleotide analogue (NUC inhibitor) identified in Feb 2020 by the WHO as the most promising candidate for treating 2019-nCoV acute respiratory disease [3,4].
Novel coronavirus (2019-nCov) is a new strain of coronavirus first identified in Wuhan City, China in Dec 2019. As a group, coronaviruses are common across the world. Typical symptoms of coronavirus include fever and a cough that may progress to a severe pneumonia causing shortness of breath and breathing difficulties. As of 9 Feb 2020, the WHO reports 37,558 confirmed cases of 2019-nCov globally (37,251 in China), and in the UK the DHSC confirmed 8 patients had tested positive [1,2].
Coronavirus disease 2019 (COVID-19)
Intravenous

Further information

Yes
To be confirmed

Trial or other data

Aug 20PIII NCT04292730 (n=596) is published; it reported day 11 clinical status distribution was significantly better for 5-day course of remdesivir vs standard care (OR, 1.65; 95% CI, 1.09-2.48; P = 0.02) but not for 10-day course vs standard care (P = 0.18). The clinical importance of these findings are uncertain [28].
Jul 20Further data announced from PIII SIMPLE-severe trial and a retrospective cohort study of patients with severe Covid-19. Claims of improved clinical recovery (74.4% of remdesivir patients by day 14 compared to 59% of standard of care patients) and 62% reduction in risk of death compared to standard of care (day 14 mortality rate reduced from 12.5% [standard of care] to 7.6% [remdesivir]. These findings need to be confirmed in clinical trials. Subgroup analyses of PIII trial results looked at safety and efficacy in a range of different ethnic groups; similar results to the overall patient population were reported. Data from the compassionate use scheme report that 83% of paediatric patients recovered by day 28, and 92% of pregnant and postpartum women recovered by day 28. No new safety issued observed. [27].
Jun 20A PII/III, open-label single-arm trial (NCT04431453) of remdesivir will soon start enrolling 50 paediatric patients with moderate-to-severe COVID-19. There will be more than 30 sites across the US and Europe. Safety and efficacy will be assessed [25].
May 20PIII ADAPTIVE COVID-19 treatment trial 2 (ACTT-II; NCT04401579) started recruitment. The study is a multicenter trial that will be conducted in up to approximately 100 sites globally. The study will compare different investigational therapeutic agents to a control arm. New arms can be introduced according to scientific and public health needs. There will be interim monitoring to allow early stopping for futility, efficacy, or safety. If one therapy proves to be efficacious, then this treatment may become the control arm for comparison(s) with new experimental treatment(s). ACTT-II will evaluate the combination of baricitinib and remdesivir compared to remdesivir alone. Subjects will be assessed daily while hospitalized. If the subjects are discharged from the hospital, they will have a study visit at Days 15, 22, and 29. The primary outcome is time to recovery by Day 29. A key secondary outcome evaluates treatment-related improvements in the 8-point ordinal scale at Day 15. Estimated primary completion date is Aug 2023 [23].
May 20Further data announced from the PIII SIMPLE trial which demonstrated that pts in the 5-day remdesivir gp were more likely to have clinical improvement at Day 11 vs. the standard of care group (OR 1.65 [95% CI 1.09-2.48]; p=0.017). The odds of improvement in clinical status with 10-days of remdesivir vs. standard of care were favorable but not statistically significant (OR 1.31 [95% CI 0.88-1.95]; p=0.18). No new safety signals were identified with remdesivir but safety may potentially have contributed to overall outcomes. Gilead plans to submit the full data for publication in a peer-reviewed journal in the coming weeks and they plan to expand the study to add another 1,000 moderately ill pts [22].
May 20Preliminary data from PIII ADAPTIVE trial (ACTT; NCT04280705) published in the NEJM [21].
Apr 20Topline results announced from from the open-label, uncontrolled, PIII SIMPLE trial of remdesivir in pts with severe COVID-19 (with pneumonia and reduced oxygen levels but not requiring mechanical ventilation). Pts receiving a 10-day course of remdesivir achieved similar improvement in clinical status vs. a 5-day course (OR: 0.75 [95% CI 0.51 – 1.12] on Day 14). Time to clinical improvement for 50% of pts was 10 days in the 5-day gp and 11 days in the 10-day gp. At Day 14, 64.5% of pts in the 5-day group and 53.8% of pts in the 10-day group achieved clinical recovery (defined as no longer requiring oxygen support and medical care or discharge from hospital). Investigators suggested that pts who received treatment earlier responded better. Clinical outcomes varied by geography. Outside of Italy, the overall mortality rate at day 14 was 7% across both treatment groups. No new safety issues were observed [18].
Apr 20A preliminary data analysis from the randomised, controlled PIII ADAPTIVE COVID-19 treatment trial (ACTT; NCT04280705; n=1063), run by the US National Institutes of Allergy and Infectious Diseases (NIAID), indicate that the median time to recovery was 11 days for pts treated with remdesivir vs. 15 days for those who received placebo (p<0.001). Results also suggested a survival benefit, with a mortality rate of 8% for pts receiving remdesivir vs. 11.6% for the placebo group (p=0.059). The study is being carried out at multiple sites worldwide, including the US, Europe and the UK [15-17].
Apr 20A snapshot of data from patients (n=61) hospitalised with Covid-19 who received remdesivir on a compassionate-use basis has been published in the NEJM [14]
Apr 20Gilead has made major mid-study changes to two PIII open-label, randomised global trials to assess the antiviral activity and safety of remdesivir vs standard of care treatment in patients with severe (NCT04292899) or moderate (NCT04292730) COVID-19, quadrupling the enrolment target (n=7,600 in total) and changing the primary endpoints to focus on the odds of improvement over 14 days on a seven-point scale that runs from death to not hospitalised [12,13].
Apr 20Gilead stop two trials in China due to "The epidemic of COVID-19 has been controlled well in China, no eligible patients can be enrolled at present." These are, a PIII trial (NCT04252664) of remdesivir in pts with mild and moderate COVID-19 and a PIII trial(NCT04257656) in pts with severe Covid. [11]
Apr 20Gilead has initiated two PIII randomised studies to evaluate the safety and efficacy of its investigational treatment remdesivir in patients with moderate to severe COVID-19 (coronavirus). The two studies which have been given urgent public health research (UPHR) status by the Chief Medical Office will initially involve 15 centres* in the UK [10].
Mar 20The World Health Organization (WHO) is putting together a multi-nation trial (SOLIDARITY) to speed up research on coronavirus treatments. It aims to generate data that can be used to determine which treatments are most effective, if they reduce mortality and time spent in the hospital, and if any pts receiving the drugs require ventilation or admission to an ICU. The trial’s design allows more drugs to be added as they become available at participating hospitals. It will consist of 5 arms: 1. standard of care, 2. remdesivir, 3. Kaletra, 4. Kaletra plus interferon beta, 5. chloraquine. Ten countries have already confirmed that they will participate in the trial: Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland and Thailand. [8]
Feb 20A randomized, placebo controlled trial to evaluate the safety and efficacy of remdesivir in hospitalized adults diagnosed with coronavirus disease 2019 (COVID-19) has begun at the University of Nebraska Medical Center (UNMC) in Omaha, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Participants must have laboratory-confirmed SARS-CoV-2 infection and evidence of lung involvement, including rattling sounds when breathing (rales) with a need for supplemental oxygen or abnormal chest X-rays, or illness requiring mechanical ventilation. Patients will be scored daily and investigators will compare participant outcomes on day 15 in both the remdesivir group and the placebo group. Data will be reviewed after the first 100 participants [7].
Feb 20The first of two PIII randomised double-blind placebo-controlled trials (NCT04257656) has begun recruitment in China to investigate efficacy and safety of remdesivir in patients (n=452 planned) with severe 2019-nCoV respiratory disease. Primary outcome is time to clinical improvement defined as the time (in days) from initiation of study treatment (active or placebo) until a decline of two categories from admission status on a six-category ordinal scale of clinical status which ranges from 1 (discharged) to 6 (death). The other study (NCT04252664) will investigate the treatment in patients (n=308 planned) with mild-moderate disease. Primary outcome measure is time to clinical recovery defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours. Patients in both trials will be followed for 28 days with estimated primary completion dates in Apr 20 [3,5].

Evidence based evaluations