Leniolisib, a Selective Phosphoinositide 3-Kinase Delta (PI3Kδ) Inhibitor, in Japanese Patients Aged 12 and Over with Activated PI3Kδ Syndrome (APDS): Data from a 12-Week, Open-Label, Single-Arm Study

Background Leniolisib is a phosphoinositide 3-kinase delta (PI3Kδ) inhibitor approved to treat activated PI3Kδ syndrome (APDS) in patients ≥12 years old in the U.S. There are no clinical data on leniolisib in Japanese APDS patients ≥12 years old. Methods This prospective, 2-part, open-label, single-arm study (NCT06249997) evaluated bodyweight-adjusted doses of leniolisib in Japanese APDS patients 12–75 years old and ≥35 kg. Part 1 co-primary endpoints were changed from baseline (CFB) to day 85 in log10-transformed sum of product of diameters (SPD) of index lymph nodes and % of naïve B cells (CD19+CD20+IgD+CD27-) out of total B cells. Results The study enrolled 3 patients: 2 received leniolisib 70 mg BID, and 1 received 50 mg BID. The mean CFB in log10-transformed index lymph node SPD was –0.41 (SD, 0.26) and mean CFB in % of naïve B cells was 7.2% (SD, 7.0); the corresponding CFB in % of CD19+CD27-CD10- naïve B cells was 32.7% (SD, 17.1). Grades 1 and 2 adverse events (AEs) and treatment-related AEs (all in the system-organ-class “Investigations”) were reported in 3 patients. No AEs were serious, and none led to leniolisib discontinuation. Conclusion Overall, leniolisib was generally well-tolerated and met the co-primary endpoints, reducing lymphoproliferation and increasing % of naïve B cells. Results in Japanese patients appear consistent with those from the pivotal trial (NCT02435173).