Pharming Group announces start of Phase II clinical trial of leniolisib for primary immunodeficiencies (PIDs) with immune dysregulation
Thursday, October 10, 2024
Pharming Group N.V. announces the start of a Phase II, proof of concept, clinical trial evaluating leniolisib in primary immunodeficiencies (PIDs) with immune dysregulation linked to altered PI3Kẟ signaling in lymphocytes.
The clinical trial is open for enrollment and will include PID patients with ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency, among others. These PID patients exhibit altered PI3Kẟ signaling in lymphocytes and likewise display similar clinical phenotypes to activated phosphoinositide 3-kinase delta syndrome (APDS) patients. Epidemiology suggests a prevalence of approximately seven patients per million in this targeted PID population, compared to one to two patients per million for APDS.
The Phase II clinical trial is a single arm, open-label, dose range-finding study to be conducted in approximately 12 patients. The objectives for the trial will be to assess safety and tolerability, pharmacokinetics, pharmacodynamics, and explore clinical efficacy of leniolisib in the targeted PID population. The trial has been designed to inform a subsequent Phase III program. The Phase II clinical trial is being 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).
Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, commented:
“The initiation of this study is an important milestone for Pharming as it represents the second primary immunodeficiency (PID) clinical program for leniolisib. Based on our experience in APDS, and the significant role of PI3Kd in regulating lymphocytes, leniolisib has the potential to address the underlying immune dysregulation and deficiency in a number of rare PID disorders with significant unmet medical needs, including ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN deficiency. We are excited to be leading this important scientific effort and to sharing the results of the study with the medical community.”
The first patient is expected to be enrolled in the study in the coming weeks.
This is the first clinical trial initiated by Pharming to study leniolisib in PIDs with immune dysregulation beyond APDS. The unique genetic drivers in ALPS-FAS, CTLA4 haploinsufficiency, NFKB1 haploinsufficiency and PTEN patients lead to enhanced PI3Kd signaling and clinical phenotypes of immune dysregulation shared with APDS. Specifically, PTEN patients with immunodeficiency are frequently described as ‘APDS-like’1, patients with ALPS-FAS display predominantly lymphoproliferative clinical manifestations with frequent cytopenic episodes2, and CTLA4 haploinsufficiency3 as well as NFKB1 haploinsufficiency4 patients demonstrate lymphoproliferative, cytopenic, and/or organ-specific autoimmune/inflammatory complications of immune dysregulation.
Leniolisib is marketed in the U.S. and approved in several other countries, for the treatment of APDS in adult and pediatric patients 12 years of age and older.
Source: globenewswire.com
