FDA Issues Complete Response Letter For Pharming’s Joenja® sNDA In Children 4–11 With Rare APDS, Citing Pediatric Dose And Batch Testing Data Needs

Pharming Group announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) regarding its supplemental New Drug Application (sNDA) for Joenja® (leniolisib) as a treatment for children aged 4 to 11 years with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency. Joenja is an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor.

The FDA’s response raised concerns about the potential for underexposure in lower weight pediatric patients. Additional pediatric pharmacokinetic data are required to reassess the proposed doses and confirm that children in lower weight groups can achieve exposure levels comparable to the approved adult and adolescent regimen. The letter also noted an issue with one of the analytical methods used for production batch testing, prompting a request for additional data and clarification.

Pharming stated that it believes these issues, both clinical pharmacology and batch testing methodology, can be addressed. The company plans to work closely with the FDA to meet the Agency’s requirements and determine the next steps for resubmission, including requesting a Type A meeting. Importantly, Joenja’s existing U.S. FDA approval for the treatment of APDS in patients aged 12 years and older remains unaffected by this regulatory action.

Fabrice Chouraqui, Chief Executive Officer of Pharming, said the company remains committed to making Joenja available to pediatric patients aged 4 to 11 with APDS. He emphasized that the therapy has the potential to address the immune dysregulation and deficiencies that drive APDS and could significantly impact the long-term course of the disease in this population, which currently has no approved targeted treatments. Chouraqui added that Pharming will work closely with the FDA to provide the necessary information and identify the most effective path forward.

The sNDA was submitted based on positive data from an open-label, multinational, single-arm Phase III study in children aged 4 to 11 years. The study showed improvements over 12 weeks in two clinically relevant hallmarks of APDS: reduced lymphadenopathy and increased naïve B cells, reflecting correction of the underlying immune defect. The submission also included safety data from eight months of treatment. Improvements were observed across all four dose levels and were consistent with results previously reported in adolescent and adult patients. All treatment-emergent adverse events were mild to moderate, there were no drug-related serious adverse events, and all patients completed the 12-week treatment period.

In October 2025, the FDA granted the application Priority Review, recognizing that Joenja could offer significant improvements in the treatment, prevention, or diagnosis of serious conditions. Currently, no approved treatments exist globally for children under 12 with APDS. Joenja received FDA approval in March 2023 for the treatment of APDS in adult and pediatric patients aged 12 years and older.