Pharming's leniolisib shows spleen and lung benefits in broader PIDs

Pharming has reported positive topline data from a Phase II study of leniolisib in patients with genetically identifiable primary immunodeficiencies (PIDs) beyond activated phosphoinositide 3-kinase delta syndrome (APDS), the indication for which the drug is already approved. The data were presented as a late-breaking poster at the 22nd Biennial Meeting of the European Society for Immunodeficiencies (ESID) in Maastricht on 14 October 2026.

The single-arm, open-label, intra-patient dose-escalation study enrolled 13 participants carrying variants in the CTLA4, SOCS1, NFKB1 or FAS genes. Nine of the 13 also carried a diagnosis of common variable immunodeficiency (CVID). Participants received leniolisib twice daily for 20 weeks, escalating from 10 mg through 30 mg to a maintenance dose of 70 mg.

Key efficacy signals

The most striking result was a mean reduction in spleen volume of 26.4%, observed in 10 of 11 evaluable participants. Splenomegaly is a clinically meaningful marker of lymphoproliferation, and consistent reductions across nearly all evaluable patients strengthen the signal considerably given the small cohort size. Lymph node index lesion size fell by a mean of 33.7% in the four evaluable participants.

Pulmonary findings were also notable. Among the seven participants with impaired gas exchange at baseline, diffusing capacity of the lungs for carbon monoxide improved by a mean of 8.0%. CT-assessed interstitial lung disease scores decreased in four of five evaluable participants. Liver stiffness improved in two of three participants with elevated baseline readings.

On safety, all treatment-related adverse events were Grade 1. Two participants experienced serious adverse events deemed unrelated to leniolisib. One participant with a history of portal hypertension discontinued early because of acute hepatitis. All 12 participants who completed the study enrolled in a three-year extension study.

"The consistent reductions in spleen volume in nearly all evaluable participants are particularly encouraging," said Anurag Relan, Chief Medical Officer of Pharming. "The trends in pulmonary findings are also particularly noteworthy, as even small improvements in progressive lung disease were not expected over such a short treatment period."

Market context and regulatory path

The commercial logic behind expanding leniolisib beyond APDS is straightforward. Pharming estimates APDS prevalence at roughly 1.5 patients per million, whereas the genetic PID subtypes studied here represent approximately 7.5 patients per million and CVID with immune dysregulation approximately 39 patients per million. Capturing even a fraction of the CVID addressable population would substantially enlarge the drug's commercial ceiling.

Leniolisib is marketed as Joenja and is already approved in multiple countries for APDS, giving Pharming an established commercial infrastructure and safety database from which to pursue label expansion. The PI3K-delta inhibitor class has faced mixed fortunes in oncology, where toxicity has constrained uptake, but the immune dysregulation PID setting involves different patient profiles and dosing regimens, and Pharming's safety data to date appear consistent with the known disease burden rather than the drug itself.

The next near-term catalyst is topline data from a separate Phase II study in CVID, which Pharming said it expects to report in November 2026. Those results will inform the company's planning for a potential registrational study in the broader CVID population. Investors and clinicians will want to see whether the CVID dataset replicates the organ-level trends observed here before drawing conclusions about a pivotal programme.