Pharming Receives Complete Response Letter from FDA for Joenja in Children Aged 4 to 11 with APDS
Pharming Group announced on Monday that the U.S. Food and Drug Administration issued a Complete Response Letter regarding its supplemental marketing authorization application for Joenja (leniolisib) in treating children aged 4 to 11 with delta phosphoinositide 3-kinase activation syndrome, a rare primary immunodeficiency. The FDA identified two issues: a risk of underexposure in younger patients of lower weight and a methodological issue concerning one of the analytical processes used for production lot testing.
FDA Concerns on Underexposure and Analytical Methods
The Food and Drug Administration raised an issue regarding potential underexposure in younger patients of lower weight. Consequently, the agency requested additional pediatric pharmacokinetic data to reassess the proposed pediatric dosages and confirm that children in the lower weight dose groups can achieve exposure levels comparable to the approved dosing regimen for adults and adolescents. The letter also identified an issue with one of the analytical methods used for production lot testing, with the FDA requesting additional data and clarifications on this point. Pharming stated that it believes it can address the clinical pharmacology and lot testing methodology issues outlined in the letter. The group indicated that it plans to work closely with the FDA to meet the agency's requirements and determine the next steps for resubmission. Pharming also mentioned that it is considering requesting a Type A meeting with the FDA. The FDA's approval of Joenja for treating APDS in patients aged 12 and older is not affected by this regulatory action.
Positive Data from Phase III Study
Pharming had submitted the supplemental authorization request to the FDA based on positive data from an open-label, multinational, single-group phase III study conducted in children aged 4 to 11 years. This study demonstrated improvements over 12 weeks in two clinically relevant features of APDS: a reduction in lymphadenopathy and an increase in naive B cells, collectively indicating a correction of the underlying immune defect. The submission also included safety data from 8 months of treatment. Improvements in lymphoproliferation and correction of the immunophenotype were observed across all four dose levels tested and were consistent with improvements previously reported in adolescent and adult patients. All adverse events that occurred during treatment were reported as mild to moderate. There were no serious drug-related adverse events, and all patients completed the 12-week treatment period. In October 2025, the FDA granted the request priority review under its guidelines indicating that the drug would offer significant improvements in the efficacy or safety of treatment, prevention, or diagnosis of serious conditions. Currently, there are no approved treatments for children with APDS under the age of 12 globally. Joenja received FDA approval for treating APDS in adult and pediatric patients aged 12 years and older in March 2023.
Global Regulatory and Clinical Status of Leniolisib
Leniolisib is an oral small molecule inhibitor of delta phosphoinositide 3-kinase approved in the United States, the United Kingdom, Australia, and Israel as the first and only targeted treatment of delta phosphoinositide 3-kinase activation syndrome in adult and pediatric patients aged 12 years and older. Leniolisib is currently under regulatory review in the European Economic Area, Japan, Canada, and several other countries for APDS. Leniolisib is also being evaluated in two phase III clinical trials in children with APDS and in two phase II clinical trials in primary immunodeficiencies with immune dysregulation. Pharming Group is a global biopharmaceutical company based in Leiden, Netherlands, dedicated to transforming the lives of patients with rare, debilitating, and potentially life-threatening diseases.
