Galapagos announces CHMP adoption of PRAC’s recommendation for Jyseleca® following extensive safety review of all JAK inhibitors

“JAK inhibitors are an important treatment option for patients based on individual benefit/risk and we see this outcome as a positive evolution in supporting the best use of the JAK inhibitor class” said Dr. Walid Abi-Saab, Chief Medical Officer of Galapagos. “Jyseleca is the only 2nd generation JAK inhibitor with JAK1 preferential inhibition of both approved doses, as well as the possibility of treating with the lowest effective dose in both RA and UC. We are very pleased with today’s outcome as we continue our mission to improve lives of people living with inflammatory diseases.”

The product labels of all JAK inhibitors will be updated to include a precautionary approach for patients aged 65 years or above, those at increased risk of major cardiovascular problems (such as heart attack or stroke), those who smoke or have done so for a long time in the past and those at increased risk of cancer. For those at-risk patients, the recommendation is that JAK inhibitors, including Jyseleca, should be used only if no suitable treatment alternatives are available. The CHMP followed PRAC’s recommendation that JAK inhibitors should be used with caution in patients with risk factors for blood clots in the lungs and in deep veins (venous thromboembolism, VTE) other than those listed above.

Following today’s CHMP opinion, filgotinib 200mg once daily remains the recommended dose for the treatment of patients with RA. For patients with UC, filgotinib 200mg once daily remains the recommended dose for induction and maintenance therapy. Dose adjustments are recommended for patients aged 65 years or above and/or at risk of major adverse cardiac events (MACE), VTE or malignancy, namely 100mg once daily dose in patients with RA, which can be escalated to 200mg in case of insufficient disease control. For at-risk patients with UC, the initiation dose remains unchanged, but a maintenance dose of 100mg should be considered. In case of a flare of disease, the dose should be escalated to 200mg once daily. For long-term treatment in patients with above risk factors, the lowest effective dose should be used.

“The recommendation by the PRAC reflects the concerns raised by the substance class mainly in older patients with rheumatoid arthritis,” said Dr. Stefan Schreiber, Professor of Medicine and Gastroenterology at the Christian-Albrechts-University in Kiel, Director of the Clinic for Internal Medicine at the University Hospital Schleswig-Holstein and Leader of Translational Inflammation Research Group in the Kiel University. “It is comforting to see that we still have the option for a benefit-oriented use of filgotinib in ulcerative colitis to provide fast anti-inflammatory efficacy to the main patient group.”

Professor Lars Erik Vølund Kristensen, Professor and CSO at the Parker Institute, University of Copenhagen and Associate Professor at Lund University, Sweden, said, "It is reassuring to see that we can still use JAK inhibitors to help a large proportion of our arthritis patients to obtain fast acting and effective anti-inflammatory treatment. I find that PRAC's recommendation harmonizes well with the concerns raised by the Oral Surveillance study, which included older rheumatoid arthritis patients with cardiovascular risk factors."

The CHMP opinion follows the recommendation of the PRAC which carried out a safety review (Article 20 procedure) of all EU-approved JAK inhibitors, including filgotinib, following the Oral Surveillance data on tofacitinib and recent data from a retrospective observational study with baricitinib. The Article 20 procedure is a specific pharmacovigilance (PV) procedure which allowed the EMA to investigate the quality, efficacy, and safety issues for one or more centrally approved products – in this case a safety review on MACE, VTE, serious infections, malignancies, and mortality for the JAK inhibitors authorised in inflammatory diseases.

The European Commission decision is expected by January 2023, approximately 60 days after today’s CHMP opinion, following which the language in the ‘special warnings and precautions for use’ and the ‘posology’ sections of the Summary of Product Characteristics (SmPC) will be updated.