Posted on 07 Jan 2020

Regulatory News - January

EMA has started review of meningioma risk with cyproterone medicines.

EMA has started a review of medicines containing cyproterone, which are used for treating a range of conditions, including excessive hair growth, prostate cancer and acne, as well as in hormone replacement therapy. The review will look into the risk of meningioma, a rare, usually non-malignant tumour of the membranes covering the brain and spinal cord. The risk of meningioma with cyproterone daily doses of 10 mg or more has been known since 2008 and information was included in the prescribing information for these medicines along with a warning that cyproterone should not be used in people who have or have had a meningioma tumour. However, there was no information at the time on the magnitude of the risk and how the risk could change with different doses. A recent study in France has now suggested that the risk of meningioma, although still very low, may be greater in those taking high doses of cyproterone for a long period. The study also showed that after patients had stopped cyproterone treatment for at least one year, the risk of developing these tumours was much reduced but remained slightly higher than usual. Due to their location in and around the brain and spinal cord, meningiomas can cause serious problems. The French medicines authority has therefore asked EMA to investigate this risk, taking into account all the latest data. EMA's safety committee (PRAC) will now examine the available evidence and make recommendations as to whether the marketing authorisations for cyproterone-containing medicines should be amended across the EU.

Review of Xeljanz (tofacitinib) - CHMP Opinion (to be used with caution in patients at high risk of blood clots).

Xeljanz is a medicine for treating adults with moderate to severe rheumatoid arthritis, a disease that causes inflammation of the joints, and psoriatic arthritis (red, scaly patches on the skin with inflammation of the joints). Xeljanz is used together with methotrexate after treatment with one or more medicines known as disease-modifying anti-rheumatic drugs (DMARDs) has not worked well enough or has led to troublesome side effects. In patients with rheumatoid arthritis, Xeljanz can also be taken alone by patients who cannot take or are intolerant to methotrexate. Xeljanz is also used to treat adults with moderate to severe ulcerative colitis, a disease causing inflammation and ulcers in the lining of the gut, after treatment with other medicines has not worked well, has stopped working or has led to troublesome side effects. Xeljanz contains the active substance tofacitinib.

Review of Lemtrada (alemtuzumab) - CHMP Opinion (restriction of its use due to reports of rare but serious side effects).

EMA is recommending restriction of the use of the multiple sclerosis medicine Lemtrada (alemtuzumab) due to reports of rare but serious side effects, including deaths. New measures to identify and manage the serious side effects are also recommended. The side effects include cardiovascular disorders (affecting the heart, circulation and bleeding as well as stroke) and immune-related disorders (caused by the body’s defence system not working properly). Lemtrada should now only be used to treat relapsing-remitting multiple sclerosis if the disease is highly active despite treatment with at least one disease-modifying therapy or if the disease is worsening rapidly. Lemtrada must also no longer be used in patients with certain heart, circulation or bleeding disorders or in patients who have autoimmune disorders other than multiple sclerosis. The medicine should only be given in a hospital with ready access to intensive care facilities and specialists who can manage serious adverse reactions. EMA has also recommended updating the physician’s guide and the patient information pack with advice on minimising the risk of serious cardiovascular disorders, which may occur shortly after a Lemtrada infusion (drip), and immune-related conditions, which may occur many months and possibly years after the last treatment. These recommendations were issued by the EMA’s safety committee (PRAC) and have now been endorsed by the Agency’s human medicines committee (CHMP). They will replace the temporary measures introduced in April 2019 while the review of Lemtrada was under way. The changes come into force when the European Commission issues its decision.

Pharmacovigilance 2030 published.

Pharmacovigilance 2030 is an invited commentary for the January 2020 “Futures” Edition of Clinical Pharmacology and Therapeutics, available open-access. The authors predict that smarter collection and reporting of ICSRs, of measurement of on-market performance of medicines, and of improved engagement of patients and healthcare professionals will be the most significant changes in pharmacovigilance by 2030. They also assume that these changes will enable faster access to life-saving treatments for patients around the world and for these treatments to be used more effectively and safely.

EMA Draft guidance - Guideline on good pharmacovigilance practices (GVP) Product- and population specific considerations III: Pregnant and breastfeeding women released.

It provides guidance to marketing authorisation applicants/holders, competent authorities of Member States and the Agency for facilitating appropriate pharmacovigilance for medicinal products that may be used in pregnancy or breastfeeding women.

4-year overview of pharmacovigilance activities in the EU

shows robust and effective medicines safety system. A report on the activities ensuring the safety of medicines carried out by EMA and the national competent authorities of the European Union (EU) Member States, Norway and Iceland from 2015 to 2018 shows that the EU pharmacovigilance system is strong and adaptable and has had a positive impact on public health. The report measures the longer-term impact of the pharmacovigilance legislation, which came into effect in July 2012, in terms of simplification of pharmacovigilance processes, improved transparency and stakeholder engagement and protection of patient health. The measurement of impact is based on a strategy and action plan for measuring the impact of pharmacovigilance activities, adopted by EMA’s safety committee (PRAC) in 2017.

EMA communication: Interactive timeline describing the journey of a medicines for human use authorised through EMA.

The European Medicines Agency has just published an interactive timeline describing the journey of a medicine for human use authorised through EMA, from initial research to discussions on patient access to medicines across the EU.

This tool is based on a booklet published earlier this year, and allows the user to navigate the content more easily. It explains in particular how EMA supports medicine development by providing scientific advice, how it assesses a medicine’s benefits and risks to decide whether it should be granted marketing authorisation, and then continues monitoring its effects when it is used by patients.

All the steps involved in these processes, including the involvement of patients, healthcare professionals and other external experts, as well as the principles guiding the scientific discussions, are outlined in the tool. This initiative aims to improve understanding of how EMA’s key procedures work.

FDA Adaptive designs for clinical trial of drugs and biologics - Guidance for industry released.

It refers to the appropriate use of adaptive designs for clinical trials to provide evidence of the effectiveness and safety of a drug or biologic; it describes important principles for designing, conducting, and reporting the results from an adaptive clinical trial.

FDA’s statement on the agency’s efforts to protect patients through post-market drug safety surveillance practices.

The statement outlines FDA’s effort to enhance the efficiency of the post-marketing safety surveillance practices. The draft document “Best Practices in Drug and Biologic Product Postmarket Safety Surveillance for FDA Staff” outlines the approach for timely post-market analyses of drugs and biologics, and includes a high-level overview of tools, methods, and signal detection and evaluation activities, using varied data sources, for drug safety surveillance to provide a broader context and a general overview of our overarching effort and commitment in this area.