The Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorization for leniolisib, marketed as Joenja, making it the first approved treatment for Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) in the UK. This approval offers a new therapeutic option for adults and adolescents aged 12 years and older, weighing 45kg or more, suffering from this rare and debilitating immune disorder.
Understanding APDS and the Need for Targeted Therapies
APDS is a rare, inherited primary immunodeficiency affecting an estimated 30 to 40 individuals in the UK. The condition arises from mutations that cause hyperactivity of the PI3Kδ pathway, leading to immune dysregulation, increased susceptibility to infections, lymphoproliferation, and an elevated risk of lymphoma. Patients typically experience recurrent respiratory infections, lymphadenopathy, and autoimmune complications, significantly impacting their quality of life and life expectancy. Current management strategies are largely supportive, focusing on infection control and symptom management, highlighting the urgent need for targeted therapies.
Leniolisib: A PI3Kδ Inhibitor Offering Targeted Intervention
Leniolisib is a small-molecule inhibitor of phosphoinositide 3-kinase delta (PI3Kδ), a key enzyme involved in immune cell signaling. By selectively inhibiting PI3Kδ, leniolisib aims to rebalance the immune system, reducing the overactivation that characterizes APDS. The recommended dose is one 70mg tablet taken orally twice daily, approximately 12 hours apart.
Clinical Evidence Supporting MHRA Approval
The MHRA's decision was primarily based on data from a 12-week, randomized, double-blind, placebo-controlled clinical trial involving 31 adult and pediatric patients with APDS. In this study, 21 patients received leniolisib 70 mg twice daily, while 10 received a placebo. The co-primary endpoints were the reduction in the size of lymph nodes and the normalization of immunophenotype. By day 85, patients treated with leniolisib demonstrated a statistically significant reduction in lymph node size and a 37% improvement in naïve B cell counts compared to placebo.
Julian Beach, MHRA Interim Executive Director of Healthcare Quality and Access, stated, "Approval of leniolisib through the IRP means we have facilitated access for people suffering from this serious disease to an effective medicine to fight infections and reduce symptoms of the disease. As with all medicines, we will keep its safety under close review."
Expedited Approval via International Recognition Procedure
The approval of leniolisib was expedited through the International Recognition Procedure (IRP), leveraging the prior approval by the US Food and Drug Administration (FDA). This mechanism allows the MHRA to consider the assessments of trusted regulatory partners, facilitating quicker access to innovative medicines for UK patients. Pharming's CEO, Sijmen de Vries, hailed the approval as an important milestone for individuals in the UK living with APDS.
Next Steps and Ongoing Evaluation
While leniolisib is now approved for use in the UK, it is currently under evaluation by the National Institute for Health and Care Excellence (NICE) for reimbursement on the NHS. Applications are also under review with other regulatory authorities globally, potentially expanding access to this novel therapy for APDS patients worldwide.
