Pharming: Leniolisib reduces spleen size by 26% in other primary immunodeficiencies
Already marketed under the name Joenja in APDS syndrome, Leniolisib was tested in 13 patients with other primary immunodeficiencies associated with immune dysregulation. Pharming presented these results on October 14, 2026, which it qualifies as positive, at the Congress of the European Society for Immunodeficiencies (ESID) in Maastricht, after announcing their acceptance as a late-breaking abstract on September 22, 2026.
Reduction in spleen and lymph node size in most evaluated patients
The open-label, dose-escalation trial in individual patients recruited participants carrying variants in the CTLA4, SOCS1, NFKB1 or FAS genes. Nine of them also had a diagnosis of common variable immunodeficiency (CVID). Patients received Leniolisib twice daily for 20 weeks, with the dose escalating from 10 mg (4 weeks) to 30 mg (4 weeks), then to 70 mg (12 weeks).
Spleen volume decreased by an average of 26.4% compared to baseline (n=11), with reduction in 10 of the 11 evaluable participants. The size of the reference lymph node lesion decreased by an average of 33.7% in the four evaluable participants. In the seven patients presenting with impaired gas exchange at baseline, the carbon monoxide diffusing capacity of the lungs (DLCO, as a percentage of predicted value) improved by an average of 8.0%.
Interstitial pneumonia scores assessed on CT scans decreased in 4 of 5 evaluable participants, and liver stiffness improved in 2 of 3 patients who presented with elevated values at baseline. For Anurag Relan, Medical Director of Pharming, the reductions in spleen volume suggest that the product acts on "a central driver of the disease process." He added that pulmonary improvements, even if limited, were not expected over such a short treatment period.
Tolerability, trial limitations, and next step in CVID
According to the company, Leniolisib was overall well tolerated across the four genotypes studied, with infections being the most frequent adverse events, with no new safety signal identified. All treatment-related adverse events were grade 1. Two participants experienced serious adverse events, considered unrelated to Leniolisib, and one patient with a history of portal hypertension discontinued treatment prematurely due to acute hepatitis.
These data are based on a trial without a control group, with several endpoints evaluated in three to five evaluable participants. The company notes that the safety and efficacy of Leniolisib have not been established in these experimental indications. All 12 participants who completed the study chose to continue treatment in the three-year extension study.
Anurag Relan stated that these results reinforce the group's strategy of evaluating PI3Kδ inhibition in primary immunodeficiencies characterized by immune dysregulation, regardless of the underlying genetic cause. Key results from a separate Phase II trial in CVID are expected in November and will guide the design of a potential registration study in the broader CVID population. According to the company's prevalence estimates, these populations represent approximately 7.5 patients per million for genetic deficiencies and approximately 39 per million for CVID (with overlap between the two), compared to approximately 1.5 per million for APDS.
