Leiden, The Netherlands – Pharming Group N.V. announced today 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 PI3Kẟ signaling submitted under the existing leniolisib IND.
The Phase 2 clinical trial will evaluate leniolisib in PIDs with immune dysregulation linked to PI3Kẟ 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 2Q 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).
Dr. Jocelyn Farmer, MD/PhD, Director, Clinical Immunodeficiency Program, Beth Israel Lahey Health, commented:
“As a physician who manages a care program for primary immunodeficiency (PID) patients, I understand the large disease burden they face, with no approved therapies to target their underlying immune dysregulation. PI3Kẟ is an important regulator of lymphocytes, and unbalanced PI3Kẟ signaling in lymphocytes is a key signature of immune dysregulation among PID patients who develop lymphoproliferative and autoimmune disease. Therefore, I am very excited to see Pharming progressing the evaluation of the PI3Kẟ inhibitor leniolisib into PIDs beyond the FDA-approved APDS indication, where it promises an opportunity to provide critical benefit to patients with a large, currently unmet, clinical need.”
Anurag Relan, Chief Medical Officer, commented:
“Today’s announcement is an exciting first step towards expanding our clinical pipeline into additional primary immunodeficiencies beyond APDS. Building upon the success of leniolisib for APDS, we believe that leniolisib will continue to have efficient uses in rebalancing immune dysregulation in PIDs. Our priority is the preparation and start of a Phase 2 clinical trial with leniolisib for targeted PID genetic disorders with immune dysregulation including CTLA4, ALPS-FAS and PTEN in the second quarter of 2024.”
About Activated Phosphoinositide 3-Kinase δ Syndrome (APDS)
APDS is a rare primary immunodeficiency that was first characterized in 2013. APDS is caused by variants in either one of two identified genes known as PIK3CD or PIK3R1, which are vital to the development and function of immune cells in the body. Variants of these genes lead to hyperactivity of the PI3Kδ (phosphoinositide 3-kinase delta) pathway, which causes immune cells to fail to mature and function properly, leading to immunodeficiency and dysregulation1,2,3 APDS is characterized by a variety of symptoms, including severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy.4,5 Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, it has been reported that people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay.6 As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma.4-7 A definitive diagnosis can be made through genetic testing. APDS affects approximately 1 to 2 people per million worldwide.
About Joenja® (leniolisib)
Joenja® (leniolisib) is an oral small molecule phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor approved in the US as the first and only targeted treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older. Joenja® inhibits the production of phosphatidylinositol-3-4-5-trisphosphate, which serves as an important cellular messenger and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Results from a randomized, placebo-controlled Phase II/III clinical trial demonstrated clinical efficacy of Joenja® in the coprimary endpoints; demonstrating statistically significant impact on immune dysregulation and normalization of immunophenotype within these patients, and interim open label extension data has supported the safety and tolerability of long-term leniolisib administration.8,9 Leniolisib is currently under regulatory review in Europe, Canada, Australia and Israel, with plans to pursue further regulatory approvals in the UK and Japan. Leniolisib is also being evaluated in two Phase III clinical trials in children with APDS. For information about Joenja®, visit: Joenja.com
About Pharming Group N.V.
Pharming Group N.V. (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. Pharming is commercializing and developing an innovative portfolio of protein replacement therapies and precision medicines, including small molecules, biologics, and gene therapies that are in early to late-stage development. Pharming is headquartered in Leiden, Netherlands, and has employees around the globe who serve patients in over 30 markets in North America, Europe, the Middle East, Africa, and Asia-Pacific.
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