Pharming widens leniolisib beyond APDS to broader PI3Kδ-driven PIDs in H2 2026 test
A 12-patient Phase 2 trial extends Pharming's approved PI3Kδ inhibitor to genetically defined immunodeficiencies with safety, not efficacy, as the registered primary endpoint.
Executive Summary
- Pharming is testing whether its approved PI3Kδ inhibitor can safely extend beyond its labeled indication into a broader set of genetically defined immune disorders driven by the same pathway.
- The registered primary endpoint is tolerability, not a comparative efficacy bar, so the readout will speak most directly to whether the drug's known safety profile holds in a sicker, more heterogeneous population.
- No other industry-sponsored trial targets PI3Kδ in this specific genetically defined population, and the closest comparator is Pharming's own second Phase 2 leniolisib study in a related immunodeficiency population, both reading out in the same half.
- The trial has moved calendar dates twice and shifted status from recruiting to active-not-recruiting on schedule, a pattern consistent with a small trial reaching its enrollment target rather than a program in distress.
The trial
NCT06549114 is enrolling patients 12 to 75 years old with pathogenic variants in SOCS1, PTEN, CTLA4, NFKB1, or FAS, or with RAS-associated leukoproliferative disorder, who present with cytopenias, splenomegaly, lymphadenopathy, or PID-related lung disease. The trial targets 12 patients, its enrollment target is unchanged from initial registration, and it is Active, not recruiting, having completed enrollment ahead of a primary completion date now set for November 1, 2026. The registered primary endpoint is the number of participants with treatment-emergent adverse events, serious adverse events, and adverse events, with 26 secondary endpoints tracking blood counts, organ involvement, and pharmacokinetics. NCT06549114Leniolisib for Immune Dysregulation in PIDsNCT06549114
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
Why leniolisib, why now
Leniolisib is approved in the United States as Joenja for activated PI3Kδ syndrome (APDS) in patients 12 and older. Pharming has described APDS as a genetically defined form within the broader common variable immunodeficiency spectrum and calls it a proof-of-concept for targeting PI3Kδ-driven immune dysregulation more broadly, framing this trial and a parallel Phase 2 study in CVID with immune dysregulation as the next test of that thesis. "Leniolisib and napazimone (KL1333) are being developed for large, underserved rare disease populations with unmet need," Chief Executive Officer Fabrice Chouraqui said, describing both programs as supported by a growing body of clinical evidence. PharmingPharming Group announces 2026 financial guidance and highlights rare disease pipeline at ...Feb 3, 2026
The timeline
The primary completion date has moved twice since the trial was first registered: from January 1, 2025 to October 1, 2025 in November 2024, and then to November 1, 2026 in February 2026, alongside the status change to active-not-recruiting. Pharming's own guidance, issued February 3, 2026, points to top-line data for both PID-linked Phase 2 trials in the second half of 2026, a window that runs from July 1 through December 31 and contains the registry's November 1 primary completion date. NCT06549114+1Leniolisib for Immune Dysregulation in PIDsNCT06549114Pharming Group announces 2026 financial guidance and highlights rare disease pipeline at ...Feb 3, 2026
The competitive frame
No other industry trial is registered for PI3Kδ in this genetically defined PID population, making NCT06549114 the only Phase 2 asset in this specific indication-target pairing. The nearest comparator is Pharming's own leniolisib trial in common variable immunodeficiency with immune dysregulation, sharing target, mechanism, modality, and sponsor. Other PI3Kδ inhibitors in clinical development, including parsaclisib, zandelisib, and duvelisib, are being tested in lymphoma and leukemia indications rather than primary immunodeficiency, so they inform tolerability of the drug class broadly but not this population directly. With no validated PI3Kδ-targeted alternative in this genetically defined PID setting, a safety profile consistent with the APDS label, paired with directional improvement across the cytopenia, organ-involvement, and lymphoproliferation secondary measures, would be the result that supports moving the drug into this broader population.
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.