FDA Accepts Pharming's sNDA for Lower-Dose Joenja in Children With APDS, Sets January 2027 Decision Date
核心洞察
The FDA has accepted Pharming's supplemental New Drug Application for lower doses of Joenja (leniolisib) in children aged 4 years and older weighing 13 kg to 27 kg with APDS.
The application received Priority Review with a PDUFA target action date of January 30, 2027, following September 2026 approval of Joenja for children weighing at least 27 kg.
The sNDA is supported by an open-label, multinational, single-arm Phase III study showing reduced lymphadenopathy and increased naive B cells over 12 weeks in children aged 4 to 11.
Pharming Group N.V. announced that the U.S. Food and Drug Administration has accepted its supplemental New Drug Application (sNDA) for lower doses of Joenja (leniolisib), an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, for children aged 4 years and older who weigh between 13 kg and 27 kg with activated phosphoinositide 3-kinase delta syndrome (搜索) (APDS). The application has been granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2027.
If approved, Joenja would be available to eligible patients aged 4 years and older with APDS who weigh 13 kg or more. The submission follows the September 2026 FDA approval expanding Joenja to children aged 4 to 11 years weighing at least 27 kg. The drug was first approved in the United States for adults and pediatric patients aged 12 years and older with APDS in March 2023.
Phase III Data Supporting the Lower-Weight Dosing
The sNDA is supported by positive data from an open-label, multinational, single-arm Phase III study in children aged 4 to 11 years. Over 12 weeks, the study showed improvements in two clinically relevant hallmarks of the condition: reduced lymphadenopathy and increased naive B cells, together indicating correction of the underlying immune defect. The submission also includes additional scientific and clinical pharmacology assessments supporting the proposed dosing in lower-weight pediatric patients.
The FDA grants Priority Review to applications for medicines that, if approved, would offer significant improvements in effectiveness or safety of the treatment, prevention, or diagnosis of serious conditions.
"Today's acceptance and Priority Review of our sNDA marks yet another important step in our efforts to expand access to Joenja for younger children living with APDS. Following the recent approval of Joenja for children aged 4 to 11 years weighing at least 27 kg, this review brings us closer to the possibility of reaching smaller children who currently are ineligible for treatment with Joenja," said Anurag Relan, Chief Medical Officer of Pharming. "We look forward to working with the FDA and making Joenja available to eligible pediatric patients as efficiently as possible."
Mechanism and Broader Development Program
Leniolisib inhibits the production of phosphatidylinositol-3-4-5-trisphosphate, an important cellular messenger that regulates cell functions including proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Results from a randomized, placebo-controlled Phase III clinical trial demonstrated statistically significant improvement in the coprimary endpoints, reflecting a favorable impact on the immune dysregulation and deficiency seen in these patients. Open-label extension data has supported the safety and tolerability of long-term leniolisib administration.
Joenja is approved as the first and only targeted treatment of APDS in adult and pediatric patients 12 years of age and older in the U.S., U.K., Australia, Israel, the EU, Canada, and South Korea; in children 4 to 11 years of age who weigh at least 27 kg in the U.S.; and for patients 4 years of age and older in Japan. Leniolisib is under regulatory review for the treatment of APDS in several other countries. It is also being evaluated in two Phase II clinical trials in primary immunodeficiencies (搜索) (PIDs) with immune dysregulation, though the safety and efficacy of leniolisib has not been established for PIDs with immune dysregulation beyond APDS.
Disease Burden and Diagnostic Delay
APDS is a rare primary immunodeficiency first characterized in 2013. It is caused by variants in either of two genes, PIK3CD (搜索) or PIK3R1 (搜索), which are vital to the development and function of immune cells. Variants of these genes lead to hyperactivity of the PI3Kδ pathway, causing immune cells to fail to mature and function properly, resulting in immunodeficiency and dysregulation.
APDS is characterized by severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy. Because these symptoms overlap with a variety of conditions, including other primary immunodeficiencies (搜索), people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay. As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma. A definitive diagnosis can be made through genetic testing. APDS affects approximately 1 to 2 people per million worldwide.