FDA Expands Leniolisib Approval to Children Aged 4 to 11 Years With APDS

The FDA approved leniolisib (Joenja; Pharming Healthcare) tablets for the treatment of activated phosphoinositide 3-kinase delta syndrome (APDS) in children aged 4 to 11 years who weigh at least 27 kg. The decision makes leniolisib the first FDA-approved treatment for children in this age and weight group with the rare genetic immune disorder.¹

Leniolisib was initially approved in March 2023 for adults and adolescents aged 12 years and older with APDS. For the newly eligible pediatric population, treatment is administered orally twice daily approximately 12 hours apart at a weight-based dose of 40, 50, or 70 mg.¹˒²

APDS Disrupts Immune Cell Development

APDS is an inborn error of immunity caused by pathogenic variants in either the PIK3CD or PIK3R1 gene. These variants lead to overactivation of the phosphoinositide 3-kinase delta (PI3Kδ) pathway, disrupting the development and function of immune cells.³

Patients frequently experience recurrent infections involving the ears, sinuses, and respiratory tract. The condition can also cause lymphoproliferation, including enlargement of the lymph nodes, tonsils, and spleen. Some patients develop cytopenias, gastrointestinal complications, or airway obstruction. APDS is also associated with an increased risk of lymphoma.¹˒³

The clinical presentation can overlap with other immune disorders, contributing to delayed or missed diagnoses. Genetic testing is required to confirm a pathogenic variant in PIK3CD or PIK3R1 and establish an APDS diagnosis.³

Leniolisib is an oral, selective PI3Kδ inhibitor designed to address the signaling abnormality underlying APDS. By inhibiting overactive PI3Kδ signaling, the medication targets immune dysregulation rather than managing individual complications alone.²˒⁴

Evidence Supporting the Pediatric Indication

The original approval of leniolisib was supported by the randomized, double-blind, placebo-controlled portion of Study 2201 (NCT02435173). The trial included 31 patients aged 12 years and older with genetically confirmed APDS. Twenty-one patients received leniolisib 70 mg twice daily and 10 received placebo for 12 weeks.¹˒⁴

The study’s coprimary end points evaluated reductions in lymphoproliferation and correction of immunophenotype, as measured by the proportion of naïve B cells among total B cells. By day 85, treatment with leniolisib reduced lymph node size and produced a 37-percentage-point improvement in the proportion of naïve B cells compared with placebo.¹˒⁴

For children aged 4 to 11 years, the FDA evaluated safety and pharmacokinetic findings from the single-arm, open-label Study LE 3301 (NCT05438407). Eight patients received the recommended weight-based dosage. Pharmacokinetic analyses found no clinically meaningful difference in leniolisib exposure between patients younger than 12 years and older patients, supporting the pediatric dosing regimens.¹˒⁵

The pediatric study adds evidence for using a targeted PI3Kδ inhibitor earlier in the course of APDS. Because the disorder is progressive, earlier treatment could reduce the period during which children remain vulnerable to recurrent infections and other complications. Continued follow-up will be important for understanding the therapy’s long-term clinical effects in younger patients.

Safety and Pharmacy Considerations

The most common adverse reactions reported among children aged 4 to 11 years included abdominal pain, respiratory tract infection, diarrhea, headache, cough, nausea, rhinitis, and alopecia. Leniolisib is not recommended for patients with moderate or severe hepatic impairment.¹˒²

Pharmacists can help families follow the twice-daily, weight-based regimen and understand that doses should be taken approximately 12 hours apart. Because the correct dose depends on body weight, pharmacists should verify the prescribed strength and monitor whether growth or weight changes require reassessment by the treating clinician.¹˒²

Medication reconciliation also remains important for identifying potential interactions and confirming that families understand how to manage missed doses. Pharmacists can reinforce that leniolisib is intended to address the underlying PI3Kδ pathway abnormality, but patients may still require monitoring and supportive care for infections or established complications of APDS.²˒³

REFERENCES

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. Joenja (leniolisib) tablets. Prescribing information. Pharming Healthcare, Inc. Revised September 2026. https://joenja.com/prescribing-information.pdf

3. Sacco K, Milner JD, Orange JS. Activated PI3K delta syndrome. GeneReviews. University of Washington, Seattle. Updated 2025. https://www.ncbi.nlm.nih.gov/books/NBK611655/

4. Rao VK, Webster S, Šedivá A, et al. A randomized, placebo-controlled phase 3 trial of the PI3Kδ inhibitor leniolisib for activated PI3Kδ syndrome. Blood. 2023;141(9):971-983. doi:10.1182/blood.2022018546

5. Study of leniolisib in pediatric patients aged 4 to 11 years with activated PI3K delta syndrome. ClinicalTrials.gov identifier: NCT05438407. Updated September 2026. https://clinicaltrials.gov/study/NCT05438407