Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28 September - 1 October 2020
PRAC reviews a signal with Veklury
Veklury has been given a ‘conditional marketing authorisation’ in the EU for the treatment of COVID-19 in adults and adolescents from 12 years of age with pneumonia who require supplemental oxygen, because the benefits to these severely ill patients outweigh the risks of making the medicine available despite having less complete data than normally expected. This means that more evidence is required to be submitted in the post-authorisation phase.
For Veklury, renal toxicity was evaluated at the time of the marketing authorisation application, primarily on the basis of animal studies. It was highlighted in the risk management plan as an important potential risk where further information was needed to better understand the effects of remdesivir on the kidney. Enhanced safety monitoring is in place to pick up reports of unwanted effects and acute kidney injury is being followed as an adverse event of special interest (AESI) in monthly summary safety reports for remdesivir.
At this stage, it has not been determined whether there is a causal relationship between Veklury and the reports of acute kidney injury. The reports form a ‘safety signal’ - information on a new or incompletely documented adverse event that is potentially caused by a medicine and that warrants further investigation.
Kidney injury can be caused by other factors as well, e.g. diabetes; importantly, COVID-19 is itself known to be a cause. The PRAC will now carefully assess all available data to evaluate if the medicine may have been responsible for the kidney problems and if there is a need to update the existing information for Veklury. Recommendations for the use of this medicine have not changed. The product information already advises doctors to monitor patients for renal impairment prior to and during treatment and not start treatment in patients with an important decrease in renal function.
EMA is reviewing any new information that becomes available through monthly summary safety reports (a tool for enhanced safety monitoring), periodic safety update reports and signal detection.
In cases where a causal relationship is confirmed or considered likely, regulatory action may be necessary and this usually takes the form of an update of the summary of product characteristics and the package leaflet. EMA will further communicate on the outcome of the PRAC’s review.
- Safety signal assessments. A safety signal is information which suggests a new potentially causal association, or a new aspect of a known association between a medicine and an adverse event that warrants further investigation. Safety signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. More information can be found under Signal management.
- Periodic safety update reports, abbreviated as PSURs, are reports prepared by the marketing authorisation holder to describe the worldwide safety experience with a medicine in a defined period after its authorisation. PSURs for medicinal products that contain the same active substance or the same combination of active substances, but have different marketing authorisations and are authorised in different EU Member States, are jointly assessed in a single assessment procedure. More information can be found under Periodic safety update reports: questions and answers.
- Risk management plans, abbreviated as RMPs, are detailed descriptions of the activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicines. Companies are required to submit an RMP to EMA when applying for a marketing authorisation. RMPs are continually updated throughout the lifetime of the medicine as new information becomes available. More information is available under Risk-management plans.
- Post-authorisation safety studies, abbreviated as PASSs, are studies carried out after a medicine has been authorised to obtain further information on its safety, or to measure the effectiveness of risk-management measures. The PRAC assesses the protocols (aspects related to the organisation of a study) and the results of PASSs. More information can be found under Post-authorisation safety studies (PASS).
- Referrals are procedures used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral related to safety of medicines, the PRAC is requested by a Member State or the European Commission to conduct a scientific assessment of a particular medicine or class of medicines on behalf of the EU. More information can be found under Referral procedures.