Pharming Group received an FDA Complete Response Letter for Joenja (leniolisib) in children aged 4–11 with APDS, citing dosing and pharmacokinetic data requests.
Written By: Pharmacally Medical News Desk
Pharming Group has received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration (FDA) for its supplemental New Drug Application (sNDA) seeking to expand the use of Joenja® (leniolisib) to children aged 4 to 11 years with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency.
The FDA’s decision was not based on concerns about the overall efficacy results but instead focused on dosing and testing issues. The agency raised the possibility of underexposure in lower-weight pediatric patients and requested additional pediatric pharmacokinetic data. This would help confirm whether younger children in smaller weight groups can achieve drug exposure levels comparable to the approved regimen in adolescents and adults. The FDA also noted a concern with one analytical method used in production batch testing and asked for further clarification and supporting data.
Pharming stated that it believes these issues can be addressed. The company plans to work closely with the FDA and intends to request a Type A meeting to determine the most effective path toward resubmission.
Importantly, Joenja’s current FDA approval remains unchanged for patients aged 12 years and older, meaning treatment access for adolescents and adults with APDS is unaffected.
Fabrice Chouraqui, Chief Executive Officer of Pharming, expressed disappointment with the outcome but reaffirmed the company’s commitment to pediatric patients. He emphasized that Joenja has the potential to address the immune dysregulation and deficiency that drive APDS, a condition for which there is currently no approved targeted therapy for children under 12 years.
The sNDA submission was supported by data from an open-label, multinational, single-arm Phase III study (NCT05438407) in children aged 4 to 11 years. Over 12 weeks, patients showed improvements in two key hallmarks of APDS: reduced lymphadenopathy and increased naïve B cells, suggesting correction of the underlying immune defect. Safety findings were also encouraging, with adverse events reported as mild to moderate, no drug-related serious adverse events, and all patients completing the treatment period. Additional safety data were available from up to eight months of therapy.
In October 2025, the FDA had granted Priority Review to the application, citing the potential for significant improvement in treatment outcomes for a serious condition. Currently, no targeted therapies are approved globally for APDS patients under 12 years of age.
APDS, first described in 2013, is caused by genetic variants in PIK3CD or PIK3R1, leading to hyperactivity of the PI3Kδ pathway. The disease is characterized by recurrent infections, lymphoproliferation, autoimmunity, and enteropathy. Due to overlapping symptoms with other immune disorders, diagnosis is often delayed by a median of seven years, increasing the risk of long-term complications such as permanent lung damage and lymphoma. APDS is estimated to affect 1 to 2 individuals per million worldwide.
Leniolisib is an oral, selective PI3Kδ inhibitor currently approved in the U.S., U.K., Australia, and Israel as the first targeted treatment for APDS in patients aged 12 years and older. The drug has shown significant clinical benefit in Phase III trials by improving immune dysregulation and deficiency, with long-term extension studies supporting its safety profile. Regulatory reviews are ongoing in Europe, Japan, Canada, and other regions, and additional studies are underway in pediatric APDS and other immune dysregulation disorders.
Pharming’s next steps will focus on generating the requested pharmacokinetic evidence and resolving batch testing concerns, with the goal of ultimately making Joenja available to younger pediatric patients living with this rare and progressive immune disorder.
References
Pharming Group receives Complete Response Letter from U.S. FDA for sNDA for Joenja® (leniolisib) in children aged 4 to 11 years with APDS, 01 Feb 2026, Pharming Group
Pediatric Patients Aged 4 to 11 Years With APDS, ClinicalTrials.gov ID NCT05438407, https://clinicaltrials.gov/study/NCT05438407