Pharming Group announced that the US Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to its supplemental New Drug Application (sNDA) for Joenja (leniolisib), an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, as a treatment for children aged four to 11 years with Activated Phosphoinositide 3-kinase Delta Syndrome (APDS), a rare primary immunodeficiency.

The FDA raised an issue with the potential for underexposure in lower weight paediatric patients. As a result, the FDA has requested additional paediatric pharmacokinetic data to reassess the proposed peadiatric doses and confirm that children in the lower weight dose groups can achieve exposure levels comparable to the approved adult and adolescent regimen. The letter also identified an issue with one of the analytical methods used for production batch testing, and the FDA requested additional data and clarification on this point.

Fabrice Chouraqui, Chief Executive Office, Pharming, commented, “While we are disappointed in the FDA’s response, we remain dedicated to making Joenja available to paediatric patients aged four to 11 with APDS. Joenja has the potential to address the immune dysregulation and deficiency that drive APDS and significantly impact the long-term course of disease in this population, for whom there is currently no approved targeted treatment. We are going to work closely with the FDA to provide the necessary information and determine the best and most effective path forward.”

Pharming submitted the sNDA to the FDA based on positive data from the open-label, multi-national, single-arm phase-III study in children aged four to 11 years, which showed improvements over 12 weeks in two clinically relevant hallmarks of APDS, reduced lymphadenopathy and increased naïve B cells, together indicating a correction of the underlying immune defect.

The submission also included safety data from eight months of treatment. The improvements in lymphoproliferation and immunophenotype correction were seen across the four dose levels investigated and were consistent with the improvements previously reported in adolescent and adult patients. All treatment-emergent Adverse Events (AEs) were reported to be mild-to-moderate in nature. There were no drug-related serious AEs, and all patients completed the 12-week treatment period.

In October 2025, the FDA granted the application priority review based on its guidelines stating the medicine would offer significant improvements in effectiveness or safety of the treatment, prevention, or diagnosis of serious conditions. Currently, there are no approved treatments for children with APDS under the age of 12 years globally. Joenja received approval from the FDA for the treatment of APDS in adult and paediatric patients 12 years of age and older in March 2023.