The Netherlands-based Pharming Group said the US FDA issued a Complete Response Letter (CRL) to its supplemental New Drug Application (sNDA) seeking approval of Joenja (leniolisib) as a treatment for children aged 4 to 11 years with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency, delaying the planned expansion of the drug’s pediatric indication. Leniolisib is an oral, selective PI3Kδ inhibitor already approved in older children and adults with APDS, and the regulatory setback highlights the challenges of extending rare-disease approvals into younger populations despite prior positive Phase III results.
The CRL follows submission of the sNDA, which was based on positive Phase III data showing improvements in immune dysregulation markers such as lymphadenopathy and naïve B-cell counts in children aged 4 to 11 years with APDS. Regulators cited concerns including potential underexposure of lower-weight children at the tested dose levels and an issue with one analytical method used in production batch testing, prompting the request for additional data before approval can be considered. The CRL does not affect Joenja’s existing approval in patients aged 12 years and older. Pharming said it will work closely with the FDA to address the agency’s questions and determine the most effective path forward for the pediatric filing.
Leniolisib, marketed as Joenja in the United States, is an oral phosphoinositide 3-kinase delta (PI3Kδ) inhibitor that modulates immune function by targeting the delta isoform of PI3K, a signaling enzyme overactive in APDS that contributes to immune dysregulation and recurrent infections. The drug received US approval in March 2023 for treatment of APDS in adult and pediatric patients aged 12 years and older, marking the first approved therapy for this ultra-rare condition.
APDS is caused by genetic variants in genes such as PIK3CD or PIK3R1, leading to abnormal PI3Kδ signaling that impairs immune cell development and function, resulting in increased susceptibility to infections, lymphoproliferation, and risk of autoimmune complications. There are currently no approved targeted therapies for children under 12 with APDS in the United States, and regulatory interactions around the extension of Joenja’s label have been closely watched by clinicians and investors. The sNDA was previously accepted for Priority Review in October 2025 with a PDUFA target action date of January 31, 2026, reflecting the unmet need in this age group.
The CRL is likely to delay potential approval and launch of Joenja in younger children, pushing back timing for any regulatory resubmission or additional data submission, which Pharming will need to discuss with the FDA in planned future meetings.