Decision

Treatment protocol on the pharmacovigilance system

Published 26 May 2020

This decision was withdrawn on 3 July 2020

Granting of conditional marketing authorisation. See expired early access to medicines scheme scientific opinions.

EAMS 11972/0001 Remdesivir 100 mg powder for concentrate for solution for infusion

EAMS 11972/0002 Remdesivir 100 mg concentrate for solution for infusion

Early Access to Medicines Scheme – Treatment protocol – Information on the pharmacovigilance system and requirements for reporting safety data

Introduction

The aim of the Early Access to Medicines Scheme (EAMS) is to provide earlier availability of promising new unlicensed medicines and medicines used outside their licence, to UK patients that have a high unmet clinical need. The medicinal products included in the scheme are those that are intended to treat, diagnose or prevent seriously debilitating or life-threatening conditions where there are no adequate treatment options. The scientific 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 the medicine 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.

As the safety profile of the EAMS medicine may not yet be fully established it is particularly important that any harmful or unintended responses to EAMS medicines are reported. Any suspected adverse drug reactions (ADRs) for patients receiving remdesivir can be reported directly to the MHRA via the new dedicated COVID-19 Yellow Card reporting site.

When reporting please provide as much information as possible, including information about medical history, any concomitant medication, onset, treatment dates, outcome and results of any test results or investigations. Alternatively, healthcare professionals can report ADRs which occur in patients directly to the pharmaceutical company who manufactures the EAMS medicine. More information about the scheme can be found on our website.

Physicians should report data on all patients receiving remdesivir under EAMS by completing the ISARIC 4C CRFs to enable systematic collection of information on clinical outcomes and adverse events.

The information below is intended for physicians and is provided by the pharmaceutical company that manufactures the EAMS medicine. It summarises the requirements for clinical monitoring and reporting of adverse events with medicines used under the scheme.

Physicians should also consult the relevant detailed information provided by the company.

EAMS Indication

Remdesivir is indicated for the treatment of adults and adolescent patients (≥12 years old) 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 extracorporeal membrane oxygenation (ECMO).

Information on the Pharmacovigilance system

DHSC (in conjunction with the NHS) will provide a list of hospitals to whom Gilead should supply drug, along with contact information for the hospital’s R&D or clinical team (to aid site initiation) and proposed COVID Clinical Lead.

Gilead will contact the hospital to provide a Welcome Pack that will include:

• EAMS Treatment Protocols
• Pharmacy Manual(s)
• Forms for completion (including safety reporting forms)
• Information from the customer services team on the ordering and delivery process

In response to the Welcome Pack, the hospital will need to return:

• Name and contact details for the COVID Clinical Lead and COVID lead pharmacist
• Pharmacy delivery address and contact number for confirmation of delivery and receipt

Following provision of the information requested in the Welcome Pack, and receipt of confirmation of any necessary approvals, an EAMS initiation teleconference will be arranged.

During this TC, hospital personnel will be provided information on the following:

• EAMS protocols including target population, inclusion/exclusion criteria, clinical procedures, discontinuation criteria
• Remdesivir, including formulation, ordering, storage, dosing, preparation for infusion
• Eligibility and assessments, including patient consent
• Adverse event reporting, including Adverse Events (AEs), Serious Adverse Events (SAEs), Special Situation Reports (SSRs)
• Clinical outcome data collection through ISARIC 4C study protocol CRFs

Any questions, or requests for further information, should be submitted to UKICOVID-19@gilead.com.

Adverse event/Adverse drug reaction reporting

In accordance with Article 83(6) of Regulation (EC) No 726/2004, the pharmacovigilance rules and responsibilities defined in Articles 24(1) of the Regulation (EC) No 726/2004 are applicable to medicinal products for which an opinion on the conditions for compassionate use has been adopted. Therefore, Gilead will ensure that these pharmacovigilance rules and responsibilities are fulfilled.

Furthermore, considering the current public health crisis and the deployment of remdesivir as an unlicensed medicine in the treatment of COVID-19, patient outcome and safety information will be sought and collected. As patients enrolled in the EAMS are in life-threatening condition, information on efficacy (or lack thereof), patient course and all adverse events, including special situation reports, are critically important to ensure patient safety.

Any suspected adverse drug reactions (ADRs) for patients receiving remdesivir can be reported directly to the MHRA via the new dedicated COVID-19 Yellow Card reporting site.

Adverse Events (AEs), Serious Adverse Events (SAEs) and Special Situation reports (SSRs) (including pregnancies) are recorded on a paper reporting form and submitted to Gilead Pharmacovigilance & Epidemiology (PVE):

• Email: Safety_FC@gilead.com
• Fax: +1-650-522-5477

All safety data will be entered into the Gilead Global Safety Database, followed up and processed as per internal procedures and applicable ICSRs submitted in accordance with regulatory reporting requirement as stipulated in GVP Module VI.

Gilead will prepare monthly expedited safety summaries as requested by the Committee for Medicinal Products for Human Use (CHMP) in connection with the CHMP opinion on the compassionate use for the remdesivir in accordance with Article 83(3) of Regulation (EC) No 726/2004. Gilead will submit the monthly safety summaries to the MHRA at the time of submission to the CHMP every month. Gilead will provide more detailed 6 monthly Periodic Safety Update Reports which will be submitted to the MHRA at the same time as they are submitted to the European Medicines Agency.

The Scientific Opinion Holder is required to send ADRs suspected to be related to the EAMS products to the MHRA within the agreed timelines

Additional information

This provision of remdesivir through EAMS is designed to provide early access to this drug to adults and adolescent patients aged ≥12 years and weighing at least 40 kg hospitalised with suspected or laboratory-confirmed SARS-CoV-2 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 extracorporeal membrane oxygenation (ECMO).

Provision is made where there is a clear unmet need, prior to licensing of the product in the U.K. The treating physician will be requested to provide information for each patient receiving remdesivir through the EAMS. Entry criteria must be met, and baseline demographic, disease severity data, treatment emergent adverse events and clinical outcomes will be provided to Gilead.

Drug registry

To capture patient clinical outcomes, the ISARIC Coronavirus Clinical Characterisation Consortium (ISARIC 4C) study protocol will be utilised with data capture within the ISARIC Registry. The ISARIC CRFs (v9.3 23APR2020) will be updated to include capture of the duration of treatment with remdesivir. All other required data fields are already recorded within the ISARIC CRFs.

Hospital personnel should report data on all patients receiving remdesivir under EAMS by completing the ISARIC 4C CRFs.

AEs, SAEs and SSRs will be captured independently of the ISARIC Registry as detailed above.

Periodic reports

Gilead will prepare monthly expedited safety summaries as requested by the Committee for Medicinal Products for Human Use (CHMP) in connection with the CHMP opinion on the compassionate use for the remdesivir in accordance with Article 83(3) of Regulation (EC) No 726/2004.

Gilead will submit the monthly safety summaries to the MHRA at the time of submission to the CHMP every month.

Gilead will provide more detailed 6 monthly Periodic Safety Update Reports which will be submitted to the MHRA at the same time as they are submitted to the European Medicines Agency.

Contact details

Details for reporting safety data:

• Email: Safety_FC@gilead.com
• Tel: +44 1223 897 500
• Fax: +1 650 522 5477

Questions once enrolling/enrolled:

• UKICOVID-19@gilead.com

General Medical Information enquiries:

• Email: UKMed.Info@gilead.com
• Tel: 08000 113 700