Interim Safety and Efficacy Outcomes of an Open-Label Long-Term Extension Study of Treatment with PI3Kδ Inhibitor Leniolisib in Pediatric Patients Aged 4-11 Years with Activated PI3Kδ Syndrome (APDS)

Leniolisib, a selective PI3Kδ inhibitor, is a Food and Drug Administration (FDA)-approved treatment for activated PI3Kδ syndrome (APDS) in patients ≥12 years weighing ≥45 kg. To determine its impact on children, patients aged 4-11 years with APDS were enrolled in a two-part, prospective, open-label, single-arm, international study to evaluate its safety and efficacy (NCT05438407). Results of 12-week treatment (part 1) were previously reported. We report safety and efficacy outcomes of the 1-year extension study. Twenty of 21 patients enrolled in part 1 transitioned to the extension. Leniolisib was administered orally twice daily with dosing based on weight at study visit, ranging from 20–70 mg. The primary endpoint was safety. Additional efficacy outcomes included change from part 1 baseline (CFB) at day (D) 252 in log10-transformed sum of product of diameters (SPD) of index lymph nodes, spleen volume, and naïve B cells. No formal statistical hypotheses were tested. Median treatment exposure was 51 weeks (range, 18–64 weeks). Median treatment compliance was 98.7% (range, 26-100%), with 2 patients ≤80%. Leniolisib was well tolerated (supplemental table). Seventeen patients had 68 adverse events (AEs). The only grade 3 AE was a femur fracture; the rest were grade 1 or 2. Two serious AEs deemed unrelated to leniolisib were reported by 1 patient each: femur fracture and lymphoid tissue operation. Six patients had 7 treatment-related AEs. No AEs led to leniolisib discontinuation. Efficacy outcomes improved at D252 of treatment. Mean CFB in log10-transformed SPD was -0.267 (SD, 0.191; n = 18; 897.1 mm2 to 487.3 mm2), corresponding to -41%. Mean CFB in spleen volume was -66.0 cm3 (SD, 56; n = 20; 242.3 cm3 to 176.3 cm3), corresponding to -25%. Mean CFB in naïve B cells (CD19+CD20+CD27-IgD+) out of total B cells was 9.7% (SD, 9.5; n = 10; 78.6% to 89.7%), corresponding to 27.0% (SD, 26.21; n = 10; 24.9% to 51.9%) in calculated naïve B cells (naïve–transitional B cells) and 25.6% (SD, 19.7; n = 8; 30.6% to 56.2%) in mature naïve B cells. Body weight–adjusted doses of leniolisib were well tolerated and maintained durable outcomes with long-term exposure in patients aged 4-11 years with APDS. Data are consistent with prior studies in adolescents and adults. Tabular data are included as downloadable supplement files.