Scienza e Tecnologia
Pharming announces first patient enrolled in pediatric clinical trial of leniolisib
At sites in the United States , Europe , and Japan , the single-arm, open-label, multinational clinical trial will evaluate the safety, tolerability, and efficacy of leniolisib in approximately 15 children aged 4 to 11 years who have a confirmed APDS diagnosis. The study's primary efficacy endpoints are a reduction in index lymph node size and an increased proportion of naïve B cells out of total B cells from baseline at 12 weeks. Secondary endpoints include an assessment of the ability of leniolisib to modify health-related quality of life based on measures of physical, social, emotional, and school functioning using a validated patient questionnaire.
Pharming plans to initiate a similar clinical trial in the third quarter of 2023 that will include children aged 1 to 6 years, with APDS, to evaluate a new pediatric formulation of leniolisib. Eligible patients enrolled in either of the pediatric trials will continue to receive leniolisib for a year after the initial 12-week treatment period through an open-label extension trial.
Pharming's program for the clinical development of leniolisib in pediatric APDS is supported by positive data from a Phase II/III clinical trial that investigated the drug as a treatment for patients with the disease aged 12 years and older. As announced on February 2, 2022 , and recently detailed in the international medical journal of the American Society of Hematology, the trial met both its co-primary endpoints, with patients who took leniolisib versus placebo achieving significant reductions in lymphoproliferation as measured by index lymph node size and increases in immunophenotype corrections as measured by the percentage of naïve B cells in peripheral blood.
During the first half of 2022, positive opinions were received from the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) on the Pediatric Investigation Plan (PIP) for leniolisib as a treatment for APDS in children. The PIP(s) included the plans for both pediatric clinical trials.
Based on the Phase II/III trial results and long-term open-label extension data, the U.S. Food and Drug Administration (FDA) is conducting a priority review of Pharming's New Drug Application for leniolisib as a treatment for adolescents and adults with APDS and has assigned a Prescription Drug User Fee Act (PDUFA) goal date of March 29, 2023 . In addition, Pharming's Marketing Authorisation Application (MAA) for leniolisib in the same patient population is under evaluation by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). Pharming expects that the CHMP will issue its opinion on the leniolisib MAA in 2H 2023.
APDS is a rare primary immunodeficiency that affects approximately 1 to 2 people per million. APDS is caused by variants in either of two genes, or , that regulate maturation of white blood cells. Variants of these genes lead to hyperactivity of the PI3Kδ (phosphoinositide 3-kinase delta) pathway. Balanced signaling in the PI3Kδ pathway is essential for physiological immune function. When this pathway is hyperactive, immune cells fail to mature and function properly, leading to immunodeficiency and dysregulation. APDS is characterized by severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy. Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay. As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma. A definitive diagnosis can be made through genetic testing.
Leniolisib is a small-molecule inhibitor of the delta isoform of the 110 kDa catalytic subunit of class IA PI3K. PI3Kδ is expressed predominately in hematopoietic cells and is essential to normal immune system function through conversion of phosphatidylinositol-4-5-trisphosphate (PIP2) to phosphatidylinositol-3-4-5-trisphosphate (PIP3). Leniolisib inhibits the production of PIP3 and PIP3 serves as an important cellular messenger activating AKT (via PDK1) and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Unlike PI3Kα and PI3Kβ, which are ubiquitously expressed, PI3Kẟ and PI3Kγ are expressed primarily in cells of hematopoietic origin. The central role of PI3Kẟ in regulating numerous cellular functions of the adaptive immune system (B-cells and, to a lesser extent, T cells) as well as the innate immune system (neutrophils, mast cells, and macrophages) strongly indicates that PI3Kẟ is a valid and potentially effective therapeutic target for immune diseases such as APDS. To date, leniolisib has been well tolerated during both the Phase 1 first-in-human trial in healthy subjects and the Phase II/III registration-enabling study in patients with APDS.
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 .
For more information, visit www.pharming.com and find us on LinkedIn.
Michael Levitan, VP Investor Relations & Corporate Communications
Heather Robertson , Investor Relations & Corporate Communications Manager
E: investor@pharming.com
Victoria Foster Mitchell / Alex Shaw / Amy Byrne
T: +44 203 727 1000
Leon Melens
T: +31 6 53 81 64 27
E: pharming@lifespring.nl
Ethan Metelenis
E: Ethan.Metelenis@precisionvh.com
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Dan Caley
E: Dan.caley@aprilsix.com
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