Pharming Group N.V. announced the expansion of its rare disease pipeline with plans to develop leniolisib for additional primary immunodeficiencies (PIDs) beyond activated phosphoinositide 3-kinase delta syndrome (APDS). Pharming has engaged with the US Food and Drug Administration (FDA) and has received feedback on its plans to develop leniolisib for PID disorders with immune dysregulation. This includes the recent FDA review of a Phase 2, proof of concept, clinical trial protocol in PIDs with immune dysregulation linked to PI3K signaling submitted under the existing leniolisib IND.

The Phase 2 clinical trial will evaluate leniolisib in PIDs with immune dysregulation linked to PI3K signaling in lymphocytes, with similar clinical phenotypes to APDS. These PID disorders are defined by loss-of-function variants in the following genes cytotoxic T-lymphocyte associated protein 4 (CTLA4), FAS (causing autoimmune lymphoproliferative syndrome or ALPS), and phosphatase and tensin homolog (PTEN), among others. The epidemiology of these targeted PID genetic disorders suggests a prevalence of approximately 5 patients per million.

The Phase 2 clinical trial is a single arm, open-label, dose range-finding study, to be conducted in approximately 12 patients and is planned to start in Second Quarter 2024. The objectives for the trial will be to assess safety and tolerability, pharmacokinetics, pharmacodynamics, and explore clinical efficacy of leniolisib in this new PID population. The trial has been designed to inform a subsequent Phase 3 program.

The Phase 2 clinical trial will be conducted at the National Institute of Allergy and Infectious Diseases (NIAID) part of the National Institutes of Health (NIH) with lead investigator Gulbu Uzel, M.D., Senior Research Physician and co-investigator V. Koneti Rao, M.D., FRCPA, Senior Research Physician, Primary Immune Deficiency Clinic (ALPS Clinic).