Regulatory Focus™ > News Articles > 2022 > 2 > Euro Roundup: EMA starts review of JAK inhibitor safety after seeing heart signal

Posted 17 February 2022 | By Nick Paul Taylor 

Euro Roundup: EMA starts review of JAK inhibitor safety after seeing heart signal

2821 The European Medicines Agency (EMA) has begun a review of the safety of Janus kinase (JAK) inhibitors after a clinical trial showed patients at risk of heart disease who took Pfizer’s Xeljanz (tofacitinib) were more likely to have a major cardiovascular problem and had a higher risk of developing cancer.
Xeljanz use was linked to a higher rate of heart attack, stroke or death due to cardiovascular disease, higher risk of cancer, and higher risk of death due to any cause, serious infections and blood clots in the lungs and deep veins, when compared to TNF-alpha inhibitors. EMA also reviewed preliminary findings from an observational trial that suggest Eli Lilly’s Olumiant (baricitinib) is associated with a higher risk of major cardiovascular problems and blood clots in the lungs and deep veins.
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) now is reviewing five JAK inhibitors, including Olumiant and Xeljanz. PRAC is also looking at Pfizer’s Cibinqo (abrocitinib), Galapagos’ Jyseleca (filgotinib) and AbbVie’s Rinvoq (upadacitinib) to see if the risks apply to all JAK inhibitors.
PRAC has looked at JAK inhibitor safety before. The committee finalized a review in 2020 in response to interim results from the Xeljanz study, leading EMA to impose measures to minimize the risks and the revision of the product information. The US Food and Drug Administration (FDA) imposed a boxed warning on Olumiant, Rinvoq and Xeljanz in relation to the risks now being assessed by PRAC and rejected Jyseleca over concerns about its safety and benefit-risk profile.
PRAC disclosed the initiation of the review, which could lead to changes to the marketing authorizations, alongside details of other updates. The committee recommended suspending marketing authorizations for hydroxyethyl-starch solutions for infusion after finding that, despite repeated efforts, the products are still being used outside the recommendations that are in place to minimize risk.
EMA Notice, More
EFPIA outlines plan to cut lag between drug approval, reimbursement
The European Federation of Pharmaceutical Industries and Associations (EFPIA) is calling for the creation of a system that enables marketing authorization holders to file pricing and reimbursement applications in all EU countries within two years of winning approval, in response to an EU consultation.
Last year, the European Commission sought feedback on revisions to the EU general pharmaceuticals legislation. The consultation, which the Commission framed as part of a push to “ensure a future-proof and crisis-resistant medicines regulatory system”, included questions on how to improve EU-wide access to affordable medicines. EFPIA pushed back against some of the proposals in its response.
In a blog post, EFPIA outlined its plan to work with EU institutions, member states and stakeholders on a system that enables pharmaceutical companies to submit pricing and reimbursement applications in all EU countries within two years of market authorization.
For the system to work, EFPIA thinks the EU needs a framework for “Equity-Based Tiered Pricing” that allows the price of innovative medicines to vary between countries based on their ability to pay. EFPIA also envisions a portal that marketing authorization holders will use to share “timely information” about “the timing and processing” of pricing and reimbursement applications in each member state. The portal is intended to shed light on why there are delays in the filing of pricing and reimbursement applications.  
The Commission has published a summary of the 478 responses it received to the consultation. In its summary of industry feedback, the Commission selected topics including the digitalization of medicines regulatory processes, the high administrative costs of marketing authorization processes and the slow response rates of regulatory agencies as areas of concern identified in the consultation.
EFPIA Post, Consultation Response, More
EDQM sets out changes to widely used European Pharmacopoeia chapter
The European Directorate for the Quality of Medicines (EDQM) has described changes to the widely used European Pharmacopoeia general chapter on chromatographic separation techniques. The new chapter is scheduled for publication in July 2022 and implementation in January 2023.
Ahead of publication in the European Pharmacopoeia, EDQM has released details of the main changes that have been made to the text for harmonization purposes. The changes reflect the pharmacopoeial harmonization text that the pharmacopeias of Europe, Japan and the US signed off on last year. EDQM said harmonization promotes “the development of individual monographs with a consistent approach.”
In light of the harmonization text, Europe is set to change details of the general chapter including the signal-to-noise ratio, the default symmetry factor range and the requirement for system repeatability in the assay.
EDQM Notice
Ireland’s HPRA updates labeling mock-up guidance to support timely licensing
Ireland’s Health Products Regulatory Authority (HPRA) has updated its guidance on submitting mock-ups for labels and leaflets. The update features notable changes including actions intended to stop reviews of mock-ups from delaying the licensing process.
In a substantial new block of text added to the guidance, HPRA explains that it reviews label mock-ups separately from new applications. Decoupling approval of label mock-ups from the issuing of the license is intended to facilitate the timely issuing of new licenses. Under that way of working, applicants can file proposed label mock-ups through a separate Article 61 (3) submission before seeking a license.   
HPRA has also split the review of the text and design of labels. Under the revised guidance, HPRA will only review label mock-ups for design, layout and readability issues. The approach puts the onus on the marketing authorization holder to ensure the text on the labeling and in the leaflet mock-ups are in line with the approved national text.
HPRA Notice, Revised Guidance
Swissmedic revises risk management guidance amid confusion over when to file
The Swiss Agency for Therapeutic Products (Swissmedic) has clarified the submission requirements for  updates to risk management plans (RMP). Swissmedic made the changes after seeing organizations file RMP updates despite not making relevant content changes that would necessitate a submission.
After identifying the problem, Swissmedic changed its guidance on the preconditions for submitting RMP updates. The revised guidance states companies only need to file RMP updates if the changes to the plan relate to the safety concerns of the medicinal product, pharmacovigilance activities or risk minimization measures. 
Swissmedic made the changes as part of a broader update to its RMP guidance. The update also added “clarifications on the obligation to submit an RMP in connection with applications for authorization” that are “based on established common practice.” Swissmedic has also added a “Switzerland-specific Annex” that “substantiates and presents any deviations as regards safety concerns or implementation of pharmacovigilance activities or risk-minimizing measures in Switzerland relating to the RMP submitted.”
Swissmedic Notice
Other news:
The French National Agency for Medicines and Health Products Safety (ANSM) has tasked Philips with completing 75% of its respiratory recall by June. Philips is aiming to replace or repair all affected devices globally by the fourth quarter but, with only 7% of French products being fixed as of 4 February, ANSM has set the company an interim goal. ANSM wants all devices repaired or replaced by December. ANSM Notice (French)


© 2022 Regulatory Affairs Professionals Society.

Discover more of what matters to you