b'The phase III study enrolled 31 patients from theits announcement of the drugs approval. The dif-U.S., Europe and Russia between the ages of 12 and ference in the adjusted mean change between leni-75 years of age with symptomatic, diagnosed APDS olisib and placebo was 25%. and at least one measurable lymph node on computed Inaddition,spleenvolumedeclinedsubstantially tomographyormagneticresonanceimaging.The more with leniolisib than placebo (adjusted mean dif-study was, and placebo-controlled using a fixed-dose ference in 3-dimensional volume [cm3], -186; 95% of 70 mg leniolisib or placebo at 12 hour intervals. CI, -297 to -76.2; P = 0.0020). Key immune cell sub-Twenty-one participants were randomized to receive sets also improved.the study drug; 10 to receive a placebo. 3 A lower percentage of participants in the leniolisib The 12-week subject-, investigator-, and sponsor- groupthanintheplacebogroupreportedstudy-blinded study included efficacy and safety assess- related adverse events, 23% and 30%, respectively, ments on days 15, 29, 57 and 85 along with phar- with most grade 1 or 2. The most common side effects macokinetic assessments on days 29, 57 and 85. Thewere headache, sinusitis and atopic dermatitis. primary endpoints were reduction in size of lymphThe FDA noted that leniolisib may cause fetal harm, nodes and increase at day 85 in the percentage ofadding that patients should be advised of the potential nave B cells out of all B cells as assessed by flowrisk to a fetus and patients pregnancy status should be cytometry. All patients had less than 48% nave Bverified before starting treatment. In addition, patients cells at study initiation. with moderate to severe hepatic impairment should Secondaryandexploratoryendpointsincludednot use leniolisib, noted the FDA.changes in bidimensional size and 3D volume of the1Lucas CL, Kuehn HS, Zhao F, Niemela JE, et. Al. Dominant-activat-spleen and liver, immunophenotyping of B- and T-celling germline mutations in the gene encoding the PI(3)K catalytic sub-subsets, and levels of serum immunoglobulins, cyto- unit p110 result in T cell senescence and human immunodeficiency. kines,chemokinesandinflammatorymarkers.TheNat Immunol. 2014 Jan;15(1):88-97. doi: 10.1038/ni.2771.researchers also measured EBV and CMV loads. 2Hanson J, Bonnen PE. Systematic review of mortality and survival By day 85 of the study, patients taking Joenjarates for APDS. Clin Exp Med. 2024 Jan 27;24(1):17. doi: 10.1007/[leniolisib]sawareductioninlymphnodesizes10238-023-01259-y.and a 37% improvement in nave B cells counts3Rao VK, Webster S, ediv A, Plebani A, et. Al. A randomized, placebo-controlled phase 3 trial of the PI3K inhibitor leniolisib for comparedtoplacebo,indicatingacorrectionofactivated PI3K syndrome. Blood. 2023 Mar 2;141(9):971-983. doi: the underlying immune defect, the FDA said in10.1182/blood.2022018546.Source: Systematic review of mortality and survival rates for APDS. Clin Exp Med. 2024 Jan 27;24(1):17. doi: 10.1007/s10238-023-01259-y.71'