Joenja (leniolisib) / Novartis, Pharming Group - LARVOL DELTA

Pediatric Patients Aged 1 to 6 Years With APDS (clinicaltrials.gov) - P3 | N=16 | Active, not recruiting | Sponsor: Pharming Technologies B.V. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2025 ➔ Apr 2025

Enrollment closed • Trial primary completion date • Pediatrics • PIK3CD • PIK3R1

Pharming Group announces upcoming presentations at the 2025 Annual Meeting of the Clinical Immunology Society (CIS) (GlobeNewswire) - "Pharming Group N.V...announces the following presentations by the Company or its collaborators at the 2025 Annual Meeting of the Clinical Immunology Society (CIS), taking place May 1-4, 2025 in Philadelphia, PA. These presentations include Phase III clinical data for leniolisib for pediatric patients aged 4-11 years with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) and insights into APDS and additional primary immunodeficiencies (PIDs) with immune dysregulation."

Clinical data • P3 data • Immunology • Primary Immunodeficiency

Pharming receives positive recommendation from NICE for Joenja (leniolisib) as a treatment for APDS (GlobeNewswire) - "Pharming Group N.V...announces that the National Institute for Health and Care Excellence (NICE) has issued positive final guidance recommending Joenja (leniolisib) for reimbursement and use within the National Health Service (NHS) in England and Wales for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older. The NICE recommendation is based on the totality of the data, including the Phase III clinical trial evaluating leniolisib..."

NICE • Immunology • Primary Immunodeficiency

Primary and Safety Outcomes of a Phase 3, Open-Label, Single-Arm, 12-Week Study of Treatment with PI3Kδ Inhibitor Leniolisib in Paediatric Patients Aged 4–11 Years With Activated PI3Kδ Syndrome (APDS) (EAACI 2025) - No abstract available

Clinical • Late-breaking abstract • P3 data • Immunology • PIK3CD

Leniolisib for Immune Dysregulation in CVID (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: Pharming Technologies B.V.

New P2 trial • Primary Immunodeficiency

Extension to the Study of Efficacy of CDZ173 in Patients with APDS/PASLI (clinicaltrials.gov) - P2/3 | N=37 | Terminated | Sponsor: Pharming Technologies B.V. | Trial completion date: Jan 2027 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2027 ➔ Jan 2025; All participant have transitioned to commercial product or compassionate use.

Trial completion date • Trial primary completion date • Trial termination • PIK3CD

When The Target Is Off The Mark: A Case of Severe APDS2 Refractory to Leniolisib (AAAAI-WAO 2025) - "Organized by the Military Allergy & Immunology Assembly."

Clinical • Immunology

Value contribution of leniolisib in the Treatment of Activated PI3Kδ syndrome (APDS) in Spain using Multi-Criteria Decision Analysis (MCDA). (PubMed, Glob Reg Health Technol Assess) - "The supporting data was considered of high quality. Based on MCDA methodology and stakeholder experience in APDS management, leniolisib is seen as a value-added treatment option compared to SoC in Spain."

Journal • Rare Diseases • PIK3CD

Expert insights on Hodgkin's lymphoma development in an activated PI3K delta syndrome patient undergoing leniolisib treatment. (PubMed, Front Immunol) - "More recently, an increasing level of interest has been shown in the use of more targeted agents such as PI3Kδ-specific inhibitors. Here, we provide expert perspective on the suspected causality of a case of lymphoma observed in a 20-year-old female patient who was included in a clinical trial of leniolisib, a PI3K inhibitor."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Immunology • Lymphoma • Oncology • Primary Immunodeficiency • Transplantation • PIK3CD

Towards Targeted Therapies in Childhood Autoimmune Cytopenias: A Report on Leniolisib Use. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • Hematological Disorders • Immunology

Report of the Italian Cohort with Activated Phosphoinositide 3-Kinase δ Syndrome in the Target Therapy Era. (PubMed, J Clin Immunol) - "This study underscores the clinical heterogeneity and challenging diagnosis of APDS, highlighting the importance of multidisciplinary management tailored to individual needs and further supporting leniolisib efficacy."

Journal • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Respiratory Diseases • PIK3CD • PIK3R1

Pediatric Patients Aged 1 to 6 Years with APDS (clinicaltrials.gov) - P3 | N=15 | Recruiting | Sponsor: Pharming Technologies B.V. | Trial completion date: Nov 2025 ➔ Feb 2026

Trial completion date • Pediatrics • PIK3CD • PIK3R1

Comparative efficacy of leniolisib (CDZ173) versus standard of care on rates of respiratory tract infection and serum immunoglobulin M (IgM) levels among individuals with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): An externally-controlled study. (PubMed, Clin Exp Immunol) - P2/3 | "The results were consistent across all sensitivity analyses, regardless of censoring, baseline infection rate definition, missing data handling, or covariate selection. These novel data provide an extended comparison of leniolisib treatment versus standard of care, highlighting the potential for leniolisib to deliver long-term benefits by restoring immune system function and reducing infection rate, potentially reducing complications and treatment burden."

Journal • Infectious Disease • Respiratory Diseases • PIK3CD

ALPS, CVID, and LGL: When Autoimmune Cytopenias Are a Marker of Underlying Immune Disease (ASH 2024) - "Koneti Rao will discuss diagnosis and management of ALPS-FAS (Autoimmune Lymphoproliferative Syndrome due to FAS variants) and APDS (Activated PI3Kinase Delta Syndrome due to PIK3CD and PIK3R1 genetic variants) including recently licensed targeted treatment for the latter using a PI3Kinsae inhibitor, leniolisib...Treatment of the hematologic complications may require frequent and episodic use of corticosteroids, and/or rituximab; splenectomy is discouraged...Immunosuppressive agents (cyclophosphamide, methotrexate and cyclosporine) constitute the foundation of first line therapy. Recent advances have led to the development of targeted approaches, including JAK-STAT inhibitors, cytokine targeting and hypomethylating agents, opening novel approaches in an otherwise incurable disease."

IO biomarker • Anemia • Endocrine Disorders • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Arthritis • Leukemia • Lymphoma • Neutropenia • Oncology • Primary Immunodeficiency • Rheumatoid Arthritis • Rheumatology • Sjogren's Syndrome • Vasculitis • CCL2 • CCL22 • CTLA4 • IKZF1 • KMT2D • NFKB2 • PIK3CD • PIK3R1 • STAT1 • STAT3 • TET2 • TNFAIP3

Beyond FAScinating: advances in diagnosis and management of autoimmune lymphoproliferative syndrome and activated PI3 kinase δ syndrome. (PubMed, Hematology Am Soc Hematol Educ Program) - "Over the last 20 years, both rapamycin and mycophenolate mofetil have been successfully used as steroid-sparing long-term measures in ALPS. Current therapeutic options for APDS/PASLI (phosphoinositide 3-kinase [PI3K]-associated senescent T lymphocytes, lymphadenopathy, and immunodeficiency) include the orally bioavailable PI3Kδ inhibitor, leniolisib, which was licensed by the US Food and Drug Administration (FDA) in 2023 for use in individuals older than 12 years as a targeted treatment. Paradigms learned from patients with rare genetic disorders like ALPS and APDS may help in exploring and streamlining molecular therapy strategies in the wider group of IEIs presenting with refractory cytopenias and lymphoproliferation."

Clinical • Journal • Review • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Lymphoma • Oncology • PIK3CD

A randomised, placebo-controlled, phase III trial of leniolisib in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS): Adolescent and adult subgroup analysis. (PubMed, Clin Immunol) - "Leniolisib was well-tolerated in both adolescents and adults. These results show leniolisib is an effective APDS treatment in both subpopulations."

Journal • P3 data • Genetic Disorders • PIK3CD

Leniolisib for Immune Dysregulation in PIDs (clinicaltrials.gov) - P2 | N=12 | Recruiting | Sponsor: Pharming Technologies B.V. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jan 2025 ➔ Oct 2025

Enrollment open • Trial primary completion date • Immunology • Primary Immunodeficiency

REDEFINING CVID: THE ROLE OF GENETIC INSIGHTS IN PRECISION THERAPY (ACAAI 2024) - "Treatment with Sirolimus and later Leniolisib (following approval for APDS) led to significant clinical improvement. Clinical trials (PMID: 36399712) have shown that Leniolisib therapy often normalizes immune cell subsets over time. We anticipate similar improvements in our patient, which would confirm the efficacy of this targeted therapy."

Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Immunology • Infectious Disease • Oncology • Otorhinolaryngology • Primary Immunodeficiency • Sinusitis • CD4 • CD8 • PIK3CD • PIK3R1

ACTIVATED PHOSPHOINOSITIDE 3- KINASE D SYNDROME INITIALLY MISDIAGNOSED AS COMMON VARIABLE IMMUNODEFICIENCY (ACAAI 2024) - "He developed severe AHAI, which was successfully treated with rituximab, sirolimus, IVIG, and steroids, and an interval PET scan showed decreasing lymphadenopathies. Rituximab was selected to treat his non-neoplastic proliferation and AIHA. Leniolisib, which is a PI3K-d inhibitor in clinical trials, was considered but deferred due to a lack of literature on its use in patients with AIHA."

Anemia • Autoimmune Hemolytic Anemia • Hematological Disorders • Infectious Disease • Oncology • Primary Immunodeficiency • CD27 • CD4 • CD8 • PIK3R1

LENIOLISIB EFFECT ON RESPONSE RATES FOR SELECT OUTCOMES IN ACTIVATED PHOSPHOINOSITIDE 3-KINASE DELTA SYNDROME (APDS) (ACAAI 2024) - "Treatment of APDS with leniolisib results in significant, persistent meaningful improvements in lymph node size, spleen volume, and percentage of naïve to total B-cell ratio. Figure 1. Proportion of Patients Meeting Responder Threshold in 6 Outcomes in Leniolisib Studies in APDS."

Anemia • Hematological Disorders • Thrombocytopenia

ACTIVATED PI3K-DELTA SYNDROME (APDS) ASSERTION CRITERIA FOR EVALUATING VARIANTS OF UNKNOWN SIGNIFICANCE IN PIK3CD OR PIK3R1 (ID 226) (ESID 2024) - "Based on our findings, the VUS mutations should be updated as pathogenic in ClinVar. A pathogenic mutation warrants consideration of Leniolisib as treatment."

Immunology • PIK3CD • PIK3R1

REPORT OF THE ITALIAN COHORT WITH ACTIVATED PHOSPHOINOSITIDE 3-KINASE DELTA SYNDROME IN THE TARGET THERAPY ERA (ID 358) (ESID 2024) - "Rapamycin, employed in 36% of patients, showed efficacy in controlling lymphoproliferation; selective PI3Kδ inhibitor leniolisib, administered in 32% of patients (follow-up 2 months - 5 years), demonstrated to be beneficial on both infections and immune dysregulation. All achieved remission. Conclusions This study underscores the clinical heterogeneity and challenging diagnosis of APDS, highlighting the importance of multidisciplinary management, tailored to individual needs, and supporting leniolisib efficacy."

Immunology • Inflammation • PIK3CD • PIK3R1

Leniolisib for Immune Dysregulation in PIDs (clinicaltrials.gov) - P2 | N=12 | Not yet recruiting | Sponsor: Pharming Technologies B.V.

New P2 trial • Immunology • Primary Immunodeficiency

Pediatric Patients Aged 4 to 11 Years With APDS (clinicaltrials.gov) - P3 | N=15 | Active, not recruiting | Sponsor: Pharming Technologies B.V. | Trial completion date: Jun 2025 ➔ Dec 2025 | Trial primary completion date: Feb 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Pediatrics • CD20 • PIK3CD

Leniolisib: a drug providing a promising avenue for the treatment of activated phosphoinositide 3-kinase δ syndrome (APDS). (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal