EMA’s safety committee (PRAC) is recommending precautionary measures for the treatment of male patients with valproate medicines. These measures are to address a potential increased risk of neurodevelopmental disorders in children born to men treated with valproate during the three months before conception. Neurodevelopmental disorders are problems with development that begin in early childhood. Valproate medicines are used to treat epilepsy and bipolar disorder. In some EU Member States they are also authorised to prevent migraine headaches.
In reaching its conclusion, the PRAC reviewed data from a retrospective observational study carried out by companies that market valproate as an obligation following a previous review of valproate use during pregnancy. The committee also considered data from other sources, including non-clinical (laboratory) studies and scientific literature, and consulted patients and clinical experts.
The PRAC latest recommendations come in addition to restrictions and other measures that are already in place to avoid valproate exposure in pregnancy, because exposed babies are at high risk of malformations and developmental problems. These measures were endorsed following a referral of valproate and related substances in 2018.
More information is available in EMA’s public health communication.
New safety information for healthcare professionals: new precautionary measures for valproate-containing medicines
The PRAC also discussed a direct healthcare professional communication (DHPC) for valproate medicines.
The DHPC will inform healthcare professionals about the potential risk of neurodevelopmental disorders in children of fathers treated with valproate in the three months prior to conception. It is recommended that valproate treatment in male patients is started and supervised by a specialist in the management of epilepsy, bipolar disorder or migraine. Valproate treatment of male patients should be reviewed regularly to consider whether it remains the most suitable treatment, particularly when the patient is planning to conceive a child.
The DHPC for valproate medicines will be forwarded to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh). When adopted, the DHPC will be disseminated to healthcare professionals by the marketing authorisation holder, according to an agreed communication plan, and published on the direct healthcare professional communications page and in national registers in EU Member States.
Start of safety review of CAR T-cell medicines
The PRAC started a signal procedure to review data on secondary malignancies related to T-cells (cancers that begin in a type of white blood cells called T-cells), including T-cell lymphoma and leukemia, for the six approved chimeric antigen receptor (CAR) T-cell medicines.
CAR T-cell based gene therapy products belong to a type of personalised cancer immunotherapies where patients' white blood cells (T-cells) are reprogrammed and reinjected to attack the cancer.
Six CAR T-cell products are approved in the European Union (EU): Abecma, Breyanzi, Carvykti, Kymriah, Tecartus and Yescarta. These medicines are used to treat blood cancers such as B-cell leukemia, B-cell lymphoma, follicular lymphoma, multiple myeloma and mantle cell lymphoma in patients whose cancer has come back (relapsed) or has stopped responding to previous treatment (refractory).
A secondary malignancy is when a patient who has cancer (current or previous) develops a second cancer different from the first cancer.
For all six CAR T-cell products, secondary malignancies were considered as an important potential risk at the time of their authorisation and included in the Risk Management Plans (RMPs). Close monitoring is already in place and the marketing authorisation holders of the approved medicines are required to regularly submit interim results from the imposed long-term safety and efficacy studies and as part of the Periodic Safety Update Reports (PSURs).
The PRAC is now reviewing all available evidence, including information on 23 cases of various types of T-cell lymphoma or leukemia in EudraVigilance, the EU database of adverse reactions to medicines, and will decide on the need for any regulatory action.
Procedure | Status | Update |
|---|---|---|
| Hydroxyprogesterone-containing medicinal products – Article-31 referral | Under evaluation | PRAC continued its assessment |