A randomised, placebo-controlled, phase III trial of leniolisib in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): Adolescent and adult subgroup analysis.

Activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) is an ultra-rare, progressive genetic disease, characterised by immune deficiency and dysregulation, affecting individuals from birth. In a 12-week phase III randomised placebo-controlled trial, leniolisib, a selective PI3Kδ inhibitor, was well-tolerated and met both co-primary endpoints (change from Baseline in log₁₀-transformed sum of product of diameters of index lymph nodes and percentage of naïve/total B cells at Day 85). Here, prespecified subgroup analyses are reported in adolescents aged 12-17 years (leniolisib, n = 8; placebo, n = 4) and adults aged ≥18 (leniolisib, n = 13; placebo, n = 6). In both subgroups, leniolisib reduced lymphadenopathy (least squares mean change versus placebo: adolescents, -0.4 versus -0.1; adults, -0.3 versus 0.1) and increased the percentage of naïve B cells (least squares mean change: adolescents, 44.5 versus -16.5; adults, 28.4 versus -1.1). Leniolisib was well-tolerated in both adolescents and adults. These results show leniolisib is an effective APDS treatment in both subpopulations.