Significant reductions in lymphadenopathy1
Significant increase in naïve B cells1-3
Log10-transformed SPD of index lesions (excluding patients with
0 lesions at baseline) at week 121,*
*The LS mean change from baseline, difference in LS mean change from baseline between Joenja and placebo and its P value, were obtained from an ANCOVA model with treatment, glucocorticoid use, and immunoglobulin replacement therapy at baseline, and baseline measurement as covariates.
†The analysis excluded 2 patients from each treatment group due to protocol deviations and 1 Joenja patient having complete resolution of the index lesion identified at baseline.
Significantly improved immunophenotype vs placebo at week 12
- In patients with <48% of naïve B cells at baseline,* the adjusted mean difference between Joenja (n=8) and placebo (n=5) in the percentage of naïve B cells out of total B cells was 37.30 (95% CI: 24.06, 50.54), P=0.0002†


At week 12, patients saw a
significant reduction in
lymphadenopathy‡ with Joenja vs placebo1

Absolute percentage of naïve B
cells over time




%
REDUCTION WITH joenja
Reduction computed based on estimates for
the adjusted mean changes.2
‡Change in index lesion size was measured using the log10-transformed SPD of the largest lymph nodes (maximum of 6) identifified as per the Cheson criteria on CT/MRI.
ANCOVA, analysis of covariance; LS, least squares; SE, standard error.
by week 4 and maintained
through week 12 with Joenja
*Cell surface markers used to distinguish naïve B cells on flow cytometry were CD19+, CD27-, and CD10-. Baseline is defined as the arithmetic mean of the baseline and day 1 values when both were available, and if either value was missing, the existing value was used.
†The analysis excluded 2 patients from each treatment group due to protocol deviations, 5 Joenja patients and 3 placebo patients with ≥48% naïve B cells at baseline, 5 Joenja patients with no day 85 measurement, and 1 Joenja patient with no baseline measurement.
CD, cluster of differentiation.








Joenja effectively helped normalize immune balance in patients with APDS1,3

Joenja significantly reduced splenomegaly3


Significant reductions in spleen by 2D and 3D analysis compared
to placebo
- The adjusted mean difference in bidimensional spleen size between Joenja (n=19) and placebo (n=9) was -13.5 cm2 (95% CI: -24.1, -2.91), P=0.0148
- The adjusted mean difference in 3D spleen volume between Joenja (n=19) and placebo (n=9) was -186 cm3 (95% CI: -297, -76.2), P=0.0020

%
REDUCTION in 3d spleen volume‡- The adjusted mean difference in bidimensional spleen size between Joenja (n=19) and placebo (n=9) was -13.5 cm2 (95% CI: -24.1, -2.91), P=0.0148
- The adjusted mean difference in 3D spleen volume between Joenja (n=19) and placebo (n=9) was -186 cm3 (95% CI: -297, -76.2), P=0.0020



Secondary measure: Spleen volume scan results of actual patient illustrate average improvement documented for patients taking Joenja
prior to treatment (spleen volume 491 mL)


after 12 weeks (spleen volume 314 mL)



‡In the PD analysis set, the mean (SD) percentage change from baseline to week 12 in 3D spleen volume (mm3) was -26.68% (12.137) with Joenja (n=19) and -1.37% (24.238) with placebo (n=9). The ANCOVA model was used with treatment as a fixed effect and log10-transformed baseline as a covariate for index and non-index lesions. The use of both glucocorticoids and IV Ig at baseline was included as
categorical (yes/no) covariates.
This analysis excluded 2 patients in each treatment group. In the Joenja group, 1 patient with a complete index lesion response was excluded, and 3 patients were excluded for no non-index lesion at baseline.
Ig, immunoglobulin; IV, intravenous; PD, pharmacodynamics.
SF-36 (Short Form 36) Survey and WPAI-CIQ (Work Productivity Activity Impairment plus Classroom Impairment Questionnaire), visual analogue scales for Physician’s Global Assessment (PGA), and Patient’s Global Assessment (PtGA), and patient narratives by investigator. Clinical relevance from these assessments was not established.
An exploratory end point showed Joenja reduced IgM levels3
- In the Joenja arm, IgM was elevated above normal limits in 6 patients at baseline, and by week 12 was reduced in all, with 50% returning to within normal limits
- In contrast, IgM was elevated above normal limits at baseline in 4 patients in the placebo arm, and by day 85 levels remained stable
or elevated, with 0% returning to within
normal limits

Mean serum IgM reduced to within normal limits


Soluble biomarkers, including IgM, were prespecified exploratory end points in the protocol. Although an observational decrease in IgM was noted in some patients, no statistical significance can be made from this analysis, and no conclusions should be drawn.
About APDS
Hyperactivity along the Pl3Kδ signaling
pathway disrupts immune cell balance,
causing immune deficiency and
immune dysregulation.1,3,4,7
Additional
Safety
of Joenja is under investigation in
the open-label extension study with
some patients receiving treatment
for as long as 5 years.1,6
et al. Disease evolution and response to rapamycin in activated phosphoinositide 3-kinase δ syndrome: The European Society for Immunodeficiencies-Activated Phosphoinositide 3-Kinase δ Syndrome Registry. Front Immunol. 2018;9:543. doi:10.3389/fimmu.2018.00543 5. Rao VK, Webster S, Dalm VASH, et al. Effective “activated PI3Kδ syndrome”—targeted therapy with the PI3Kδ inhibitor leniolisib. Blood. 2017;130(21):2307-2316. doi:10.1182/blood-2017-08-801191 6. US National Library of Medicine. ClinicalTrials.gov/NCT02859727. 7. Angulo I, Vadas O, Garçon F, et al. Phosphoinositide 3-kinase δ gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866-871. doi:10.1126/science.1243292