FDA approves leniolisib for children aged 4 to 11 with APDS

According to a new announcement from Pharming, the FDA has approved leniolisib (Joenja) for children aged 4 to 11 years weighing at least 27 kg with activated phosphoinositide 3-kinase delta syndrome (APDS). The approval covers new 40 mg and 50 mg twice-daily dosing strengths and marks the first FDA-approved treatment for this pediatric age group. Leniolisib was previously approved in March 2023 for patients 12 years and older with APDS.¹

Before this approval, pediatricians managing APDS in children aged 4 to 11 years could offer only symptom management and diagnostic support, without an agent addressing the underlying PI3Kδ pathway. APDS drives significant immune dysregulation and recurrent sinopulmonary infections, which over time can lead to permanent lung damage and other complications.² The expanded indication gives pediatricians a new tool for early disease intervention in a population previously without a targeted option.

Regulatory support for the expanded pediatric indication comes from a multinational, open-label, single-arm phase 3 study of leniolisib in children aged 4 to 11 years with APDS. An NCT number was not disclosed in the announcement. This single-arm pediatric study is distinct from the randomized, placebo-controlled phase 3 trial supporting the original 2023 approval in patients aged 12 years and older.³

Over 12 weeks of treatment, investigators observed improvement in two hallmarks of APDS: reduced lymphadenopathy and increased naive B cell counts. Together, these findings indicate an improvement in the underlying immune defect driving the syndrome, rather than symptom control alone. Exact effect sizes and statistical comparisons were not included in the announcement.

The July 30 submission of a separate sNDA, seeking approval of lower doses for children aged 4 to 11 years weighing 13 kg to less than 27 kg, signals Pharming's intent to extend leniolisib access further down the pediatric weight range.

Safety profile and access timeline for pediatric leniolisib dosing

The safety profile of leniolisib in children aged 4 to 11 years was consistent with prior experience in older patients. All treatment-emergent adverse events reported in the pediatric study were mild to moderate in severity, and no drug-related serious adverse events were observed. The most common adverse reactions in patients aged 4 to 11 years weighing 27 kg or greater were abdominal pain, cough, and respiratory tract infection.

Neutropenia remains a monitoring consideration across the labeled population. Seven of 21 patients aged 12 years and older and 5 of 8 patients aged 4 to 11 years weighing at least 27 kg developed an absolute neutrophil count between 500 and 1,500 cells/microL after starting leniolisib. No patients developed an ANC below 500 cells/microL, and no neutropenia-related infections were reported.

Newly approved doses of leniolisib are expected to reach eligible pediatric patients in the United States in October 2026, distributed through Pharming's existing specialty pharmacy network and patient-support infrastructure. For children weighing 13 kg to less than 27 kg, no approved dosing currently exists, and the pending lower-dose sNDA submitted in July 2026 aims to close this gap.

"To give children living with APDS the best chance at a healthier future, early disease intervention is critical," Eveline Wu, MD, MSCR, associate professor of pediatrics at the University of North Carolina at Chapel Hill, said in a news release. "With the approval of Joenja for this pediatric population, we can now take that support even further to address the underlying pathway of disease, with the goal of reducing symptoms and preventing the irreversible complications that often arise with APDS."¹

For pediatricians, this approval adds leniolisib as a disease-modifying option for patients aged 4 to 11 years with APDS, rather than management of infections and complications alone. Availability begins in October 2026 through Pharming's specialty distribution network.

1. FDA approves Pharming’s Joenja® as first treatment for children with APDS in the U.S. News release. Pharming. September 11, 2026. Accessed September 11, 2026. https://www.pharming.com/our-news/fda-approves-pharming-joenja-as-first-treatment-for-children-with-apds-in-the-us
2. Coulter TI, Chandra A, Bacon CM, et al. J Allergy Clin Immunol. 2017;139(2):597-606.e4. doi:10.1016/j.jaci.2016.06.021
3. Rao VK, Webster S, Šedivá A, et al. Blood. 2023;141(9):971-983. doi:10.1182/blood.2022018546