Information for Medical Directors
Published 26 May 2020
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This publication is available at https://www.gov.uk/government/publications/early-access-to-medicines-scheme-eams-scientific-opinion-remdesivir-in-the-treatment-of-patients-hospitalised-with-suspected-or-laboratory-confirme/information-for-medical-directors
Information for Medical Directors
Regarding EAMS scientific opinion for Remdesivir 100 mg powder for concentrate for solution for infusion and Remdesivir 100 mg concentrate for solution for infusion is indicated for the treatment of adults and adolescent patients aged ≥ 12 years and weighing at least 40 kg hospitalised with suspected or laboratory confirmed SARS-CoV-2 infection and severe disease.
Patients with severe disease are those with an SpO2 ≤ 94% on room air or requiring supplemental oxygen or requiring non-invasive or invasive ventilation or extracorporal membrane oxygenation (ECMO).
The aim of the Early Access to Medicines Scheme (EAMS) is to provide earlier availability of promising unlicensed medicines to UK patients that have a high unmet clinical need. A positive scientific opinion is only issued by the MHRA if the criteria for the EAMS are fulfilled, which includes demonstrating a positive benefit risk balance (quality, safety and efficacy assessment) and the ability of the pharmaceutical company to supply a medicine according to a consistent quality standard.
EAMS medicines are unlicensed medicines. The term ‘unlicensed medicine’ is used to describe medicines that are used outside the terms of their UK licence or which have no licence for use in the UK. GMC guidance on prescribing unlicensed medicines can be found on the General Medical Council’s website.
The opinion is based on assessment of the information supplied to the MHRA on the benefits and risks of the medicine. As such this is a scientific opinion and should not be regarded as a licensed indication or a future commitment by the MHRA to licence such a medicine, nor should it be regarded as an authorisation to sell or supply such a medicine. A positive scientific opinion is not a recommendation for use of the medicine and should not be interpreted as such. Under EAMS the risk and legal responsibility for prescribing a ‘special’ remains with the physician, and the opinion and EAMS documentation published by the MHRA are intended only to inform physicians’ decision making and not to recommend use. An EAMS scientific opinion does not affect the civil liability of the manufacturer or any physician in relation to the product. Whilst the scientific opinion is for use of the product to treat COVID-19, the opinion has been issued under EAMS and is not an exceptional authorisation or recommendation in response to the pandemic.
EAMS procedural assessment at the MHRA
A full assessment of the quality, safety and efficacy of Remdesivir has been conducted by the MHRA’s assessment teams, including pharmacists, toxicologists, statisticians, pharmacokinetic and medical assessors. This assessment process also includes consideration of the quality, safety and efficacy aspects by the UK independent expert committees including Expert Advisory Groups (EAGs) and the Commission on Human Medicines (CHM):
- The Commission on Human Medicines (CHM) advises ministers on the quality, safety and efficacy of medicinal products. The Chair and Commissioners are appointed in accordance with the Code of Practice for Ministerial Appointments to Public Bodies. The Chair and Commissioners follow a code of practice, in which they are precluded from holding personal interests. The Commission is supported in its work by Expert Advisory Groups (EAGs), covering various areas of medicine.
- Chemistry, Pharmacy and Standards EAG, which advises the CHM on the quality in relation to safety and efficacy of medicinal products
Pharmacovigilance system
A pharmacovigilance system for the fulfilment of pharmacovigilance tasks has been put in place for this EAMS medicine, including a risk management plan. As the safety profile of the EAMS medicine is not fully established it is particularly important that any harmful or unintended responses to EAMS medicines are reported. Physicians should be aware of their obligations to report adverse event information upon enrolment of any patients receiving EAMS medicines in the scheme. They will be required to follow the process which the pharmaceutical company which manufactures the EAMS medicine has in place to enable systematic collection of information on adverse events.
For more detailed information on this EAMS medicine, please refer to the Public Assessment Report, EAMS treatment protocol for healthcare professionals, EAMS treatment protocol for patients and EAMS treatment protocol for pharmacovigilance.
Justification for the fulfilment of the EAMS criteria
There are four EAMS criteria that need to be fulfilled before a medicine can enter the scheme and a positive scientific opinion is issued by the MHRA. The fulfilment of the criteria for this particular medicine is described below.
1.1 Life threatening condition
COVID-19 is an acute viral infection affecting primarily the respiratory tract and was first detected in Wuhan, China, in December 2019. The infection, caused by SARSCoV-2, leads to respiratory illness and readily spreads from person to person.
Common signs of infection include fever, cough, shortness of breath, breathing difficulties, and other respiratory symptoms. In severe cases, SARS-CoV-2 can cause pneumonia, acute lung injury (ALI) including severe acute respiratory distress syndrome (ARDS), kidney failure, and death.
1.2 High unmet need: there is no method available/approved medicinal product
There is an urgent unmet need for the treatment of pandemic COVID-19, a condition with a significant mortality in particular in the elderly population and those with preexisting conditions. The availability of a potentially effective antiviral agent with a favourable benefit/risk profile could address this serious unmet medical need.
2. The medicinal product offers major advantage over existing methods in the UK
The applicant provided evidence to demonstrate that remdesivir represents a major advantage over currently used treatment methods in the UK. In summary, top line results of an RCT (ACTT) comparing remdesivir to placebo resulted in a reduced time to recovery from 15 days to 11 days in patients with severe COVID-19. There was a trend to reduced mortality, but this did not reach statistical significance but is considered clinically relevant. Remdesivir reduced the risk of dying (Hazard ratio 0.688, 95% CI 0.465 to 1.017, p=0.059).
3. The potential adverse effects of the medicinal product are outweighed by the benefits, allowing for a conclusion of a positive benefit/risk balance
The MHRA considers the risk benefit balance to be positive for adult and adolescent patients with severe COVID-19. This evaluation takes into account the threat and risk posed by the ongoing COVID-19 pandemic to patients and public health.
4. The company is able to supply the product and to manufacture it to a consistent quality standard, including the presence of appropriate GMP certification.
The company has provided all documentation necessary to prove that the EAMS medicine is manufactured/packaged according to GMP.