Pharming Group Initiates Phase II Trial of Leniolisib for Primary Immunodeficiencies
核心洞察
Pharming Group has commenced a Phase II clinical trial to assess leniolisib in primary immunodeficiencies (搜索) (PIDs) with immune dysregulation.
The trial will focus on PIDs like ALPS-FAS (搜索), CTLA4 haploinsufficiency (搜索), NFKB1 haploinsufficiency (搜索), and PTEN deficiency (搜索), which have a higher prevalence than APDS (搜索).
This open-label, dose range-finding study, involving approximately 12 patients, will evaluate safety, tolerability, pharmacokinetics, and clinical efficacy.
Pharming Group N.V. has announced the initiation of a Phase II clinical trial to investigate leniolisib for the treatment of primary immunodeficiencies (搜索) (PIDs) characterized by immune dysregulation linked to altered PI3Kδ (搜索) signaling in lymphocytes. The trial, conducted at the National Institutes of Health (NIH), aims to assess the safety, tolerability, and efficacy of leniolisib in patients with various PIDs, including ALPS-FAS (搜索), CTLA4 haploinsufficiency (搜索), NFKB1 haploinsufficiency (搜索), and PTEN deficiency (搜索).
These targeted PIDs exhibit a prevalence of approximately seven patients per million, which is notably higher than the one to two patients per million observed for activated phosphoinositide 3-kinase delta syndrome (APDS (搜索)). This study represents Pharming's second clinical program focusing on PIDs for leniolisib, building upon its current approval for treating APDS in adults and pediatric patients aged 12 and older.
Trial Design and Objectives
The Phase II trial is designed as a single-arm, open-label, dose range-finding study involving approximately 12 patients. The primary objectives include evaluating the safety, tolerability, pharmacokinetics, and pharmacodynamics of leniolisib in the specified PID population. Furthermore, the trial will explore the clinical efficacy of leniolisib in addressing the underlying immune dysregulation associated with these conditions.
According to Anurag Relan, MD, MPH, Chief Medical Officer of Pharming, "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 (搜索), 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 (搜索), CTLA4 haploinsufficiency (搜索), NFKB1 haploinsufficiency (搜索) and PTEN deficiency (搜索)."
Rationale for Leniolisib in PIDs
The rationale for exploring leniolisib in these PIDs stems from the shared clinical phenotypes with APDS (搜索), particularly the altered PI3Kδ (搜索) signaling in lymphocytes. Genetic factors in ALPS-FAS (搜索), CTLA4 haploinsufficiency (搜索), NFKB1 haploinsufficiency (搜索), and PTEN deficiency (搜索) lead to enhanced PI3Kδ signaling, resulting in immune dysregulation similar to that observed in APDS. PTEN patients with immunodeficiency are often described as 'APDS-like', while ALPS-FAS patients predominantly display lymphoproliferative clinical manifestations with frequent cytopenic episodes. CTLA4 and NFKB1 haploinsufficiency patients exhibit lymphoproliferative, cytopenic, and/or organ-specific autoimmune/inflammatory complications of immune dysregulation.
About Leniolisib
Leniolisib is an oral small molecule inhibitor of phosphoinositide 3-kinase delta (PI3Kδ (搜索)). It is approved in the U.S. and several other countries as a targeted treatment for activated phosphoinositide 3-kinase delta syndrome (APDS (搜索)) in adult and pediatric patients 12 years and older. Leniolisib functions by inhibiting the production of phosphatidylinositol-3-4-5-trisphosphate, a crucial cellular messenger involved in regulating cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Clinical trial data have demonstrated statistically significant improvements in co-primary endpoints, indicating a favorable impact on immune dysregulation and deficiency in APDS patients. Leniolisib is currently under regulatory review in the European Economic Area, Canada, and Australia for APDS, with plans for further regulatory approvals in Japan and South Korea.