FDA Approves Leniolisib for Children 4 to 11 Years With APDS

The FDA approved the 40-mg and 50-mg twice daily doses of leniolisib (Joenja), an oral, selective PI3Kδ inhibitor, for the treatment of children aged 4 to 11 years weighing at least 27 kg with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency. With this approval, leniolisib becomes the first FDA-approved treatment for children aged 4 to 11 years with APDS in the US. The newly approved doses are expected to reach eligible pediatric patients in October through Pharming's specialty distribution network and patient-support infrastructure.¹

The approval expands the leniolisib indication to include children aged 4 to 11 who weigh at least 27 kg with APDS. Separately, Pharming submitted another supplemental new drug application on July 30 seeking approval of lower leniolisib doses for pediatric APDS patients aged 4 to 11 years who weigh 13 kg to less than 27 kg.

"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.¹ "Previously, our best approach for children aged 4 to 11 years with APDS was to provide an accurate diagnosis and a treatment plan to manage the symptoms of APDS. 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."

Clinical Data Supporting the Pediatric Indication

The approval is supported by data from a multinational, open-label, single-arm phase 3 study in children aged 4 to 11 years with APDS. The study demonstrated improvements over 12 weeks in reduced lymphadenopathy and increased naïve B cells, together indicating an improvement in the underlying immune defect. The safety profile was consistent with prior leniolisib experience. All treatment-emergent adverse events were mild to moderate, and no drug-related serious adverse events were observed.¹

The pediatric approval builds on the trial that supported leniolisib’s original 2023 clearance. That approval, covering adult and pediatric patients 12 years of age and older weighing at least 45 kg, was based on the placebo-controlled portion of Study 2201 (NCT02435173), a 12-week, blinded, randomized trial of 31 patients with confirmed APDS-associated PIK3CD or PIK3R1 variants.²

Twenty-one patients received 70 mg of leniolisib and 10 received a placebo twice daily. The coprimary end points were improvement in lymphoproliferation, measured as a reduction in index lymph node size, and normalization of immunophenotype, measured as the percentage of naïve B cells among total B cells. By day 85, patients taking leniolisib saw a reduction in lymph node size and a 37% improvement in naïve B cell counts compared with placebo, indicating correction of the underlying immune defect.²

A separate analysis of that same trial found that 26% of patients in the leniolisib group achieved complete absence of their index lymphadenopathy, and the remaining 74% achieved a partial response. In the placebo group, 45% achieved a partial response, 44% had stable disease, and 11% had an unknown response. Leniolisib also reduced splenomegaly more than placebo did, and the mean serum IgM level in the leniolisib arm fell 208.26 mg/dL from baseline by day 85, compared with a 10.00 mg/dL decline in the placebo arm.³

Safety Considerations

The most common adverse reactions occurring in more than 10% of patients were headache, sinusitis, atopic dermatitis, and weight gain in adult and pediatric patients 12 years of age and older, and abdominal pain, cough, and respiratory tract infection in pediatric patients from 4 years to younger than 12 years who weigh 27 kg or greater. Seven patients (33%) 12 years of age and older and 5 patients (63%) aged 4 to 12 years weighing 27 kg or greater developed an absolute neutrophil count between 500 and 1500 cells/µL after receiving Joenja, though no patients developed a count below 500 cells/µL, and no infections associated with neutropenia were reported.^1-3

Prescribers should verify pregnancy status in females of reproductive potential before starting leniolisib, since the drug may cause fetal harm; patients should use highly effective contraception during treatment and for 1 week after the last dose and should not breastfeed during that same window. Live, attenuated vaccines may be less effective when administered during leniolisib treatment, and the drug may cause hypersensitivity reactions, including anaphylaxis. Leniolisib is not recommended for patients with moderate to severe hepatic impairment, and clinicians should avoid coadministering it with strong CYP3A4 inhibitors, strong or moderate CYP3A4 inducers, or BCRP, OATP1B1, and OATP1B3 substrates. Joenja is now available in 40-mg, 50-mg, and 70-mg tablets.^1-3

Disease Background and Pharmacy Relevance

APDS is an inborn error of immunity caused by variants in either the PIK3CD or PIK3R1 gene, which lead to hyperactivation of the PI3Kδ signaling pathway and impair normal B- and T-cell maturation and function.^1,3 The condition is inherited in an autosomal dominant pattern.

Because APDS symptoms overlap with other primary immunodeficiencies, patients are frequently misdiagnosed and experience a median 7-year diagnostic delay, a lag that can allow damage such as permanent lung disease and lymphoma to accumulate before treatment begins. Pharming estimates APDS affects approximately 1 to 2 people per million worldwide, while GeneReviews places the estimated prevalence at around 1 in 1 million.^1,3

For pharmacists, the pediatric approval adds two new tablet strengths, 40 mg and 50 mg, to the existing 70-mg tablet used in patients 12 years and older, which will require attention to correct strength dispensing as younger patients transition onto therapy.¹

Leniolisib is the recommended first-line targeted therapy for APDS patients with significant lymphoproliferative disease, including lymphadenopathy and splenomegaly, ahead of sirolimus or allogeneic hematopoietic stem cell transplant, which are reserved for cases where leniolisib is unavailable or disease is severe and treatment-refractory.³

Leniolisib is distributed through Pharming's specialty pharmacy network rather than through general retail channels, which pharmacists should factor into counseling and refill-timing conversations with families.¹

Vanessa Tenembaum, CEO of the Jeffrey Modell Foundation, an international, nonprofit organization dedicated to helping individuals and family members affected by primary immunodeficiency disorders, said the approval addresses a population whose disease does not pause for treatment gaps.¹

"APDS is not a disease that waits. It can affect important aspects of childhood, potentially impacting time in school, time with friends, and other activities of daily life," Tenembaum said.¹ "This approval is a meaningful step forward because it gives younger patients and their physicians another much-needed option earlier in the disease journey. For families living with APDS, it means more than progress; it means renewed hope, greater possibility, and a clearer path forward."

REFERENCES

1. Pharming Group N.V. FDA approves Pharming's Joenja® as first treatment for children with APDS in the U.S. News release. Pharming Group N.V. September 11, 2026. Accessed September 14, 2026. https://www.globenewswire.com/news-release/2026/09/11/3360484/0/en/fda-approves-pharming-s-joenja-as-first-treatment-for-children-with-apds-in-the-u-s.html

2. US Food and Drug Administration. FDA approves first treatment for activated phosphoinositide 3-kinase delta syndrome. March 24, 2023. Accessed September 14, 2026. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-activated-phosphoinositide-3-kinase-delta-syndrome

3. Ali A, Qureshi A, Shigri AF, Alvi AM, Malikzai A. Leniolisib: a drug providing a promising avenue for the treatment of activated phosphoinositide 3-kinase δ syndrome (APDS). Ann Med Surg. 2024;86:3812-3813. doi:10.1097/MS9.0000000000002189

4. Sacco K, Uzel G. Activated PI3K Delta Syndrome. In: Adam MP, Bick S, Mirzaa GM, et al., eds. GeneReviews® [Internet]. University of Washington, Seattle; January 30, 2025. Accessed September 14, 2026. https://www.ncbi.nlm.nih.gov/books/NBK611655/