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

A Diagnostic Challenge in Activated PI3K-Delta Syndrome: Multisystem Inflammatory and Infectious Mimicry (ACG 2026) - "Case Description/ A 50 year old female from the Dominican Republic with APDS 2 on IgG and leniolisib history of childhood toxoplasmosis recurrent sinopulmonary infections mastoiditis otitis media and duodenal ulcer disease presented with 4 days of fever night sweats diffuse abdominal pain and 2 days of diarrhea.She previously required hospitalization for GBS pharyngitis with bacteremia complicated by abdominal pain submandibular swelling odynophagia diarrhea and hematochezia...She was treated with IV acyclovir fluconazole and Bactrim prophylaxis...Broad differential diagnosis and multidisciplinary management are essential when standard diagnostics remain unrevealing. Figure: Upper GI tract nasopharynx/oropharynx abnormal Figure: lower third of the esophagus and GE junction"

Candidiasis • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Otorhinolaryngology • Peptic Ulcer • Primary Immunodeficiency • Respiratory Diseases • PIK3CD

Pharming…announced that the U.S. Food and Drug Administration (FDA) has accepted its supplemental New Drug Application (sNDA) seeking approval for lower doses of Joenja (leniolisib), an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor… (GlobeNewswire) - "...for children aged 4 years and older who weigh between 13 kg and 27 kg with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency. The application has been granted Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) target action date of January 30, 2027. The sNDA is supported by positive data from an open-label, multinational, single-arm Phase III study in children aged 4 to 11 years, which showed improvements over 12 weeks in two clinically relevant hallmarks of the condition, reduced lymphadenopathy and increased naive B cells, together indicating correction of the underlying immune defect."

FDA filing • PDUFA • Priority review • Immunology

Leniolisib for Immune Dysregulation in CVID (clinicaltrials.gov) - P2 | N=27 | Completed | Sponsor: Pharming Technologies B.V. | Active, not recruiting ➔ Completed | N=20 ➔ 27

Enrollment change • Trial completion • Primary Immunodeficiency • CARD11 • CD20 • CD81 • CTLA4 • CTNNB1 • IKZF1 • NFKB2 • PTEN • SEC61A1 • TNFRSF13B • TNFRSF13C • TNFSF12

Associations Between Short-Term Changes in Disease Activity and Long-Term Clinical Outcomes in Activated Phosphoinositide 3-Kinase Delta Syndrome. (PubMed, J Immunol Res) - "In this clinical trial setting, short-term improvements in immunodeficiency and dysregulation following treatment with leniolisib were associated with longer-term improvements in clinical outcomes, including infection rates and quality of life, for patients with APDS."

Clinical • Clinical data • Journal • Infectious Disease • Rare Diseases • PIK3CD

Long-term Safety and Efficacy of Leniolisib in PIDs With Immune Dysregulation (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Pharming Technologies B.V. | Trial completion date: Apr 2029 ➔ Aug 2029 | Trial primary completion date: Sep 2028 ➔ Aug 2029 | Recruiting ➔ Active, not recruiting

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

Pharming…announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental New Drug Application (sNDA) for 40 mg and 50 mg twice-daily dosing of Joenja (leniolisib)…as a treatment for children aged 4 to 11 years weighing at least 27 kg with activated phosphoinositide 3-kinase delta syndrome (APDS) (GlobeNewswire) - "The newly approved Joenja doses are expected to be available to eligible pediatric patients in the U.S. in October through Pharming’s established specialty distribution network and patient-support infrastructure. On July 30, Pharming also submitted a separate sNDA seeking approval of lower Joenja doses for pediatric APDS patients aged 4 to11 years who weigh 13 kg to less than 27 kg....Today’s approval is supported by data from a multinational, open-label, single-arm Phase III study in children aged 4 to 11 years with APDS."

FDA approval • FDA filing • Launch US • Immunology • Primary Immunodeficiency

APDS treatment in Germany: decision criteria, costs and contribution of leniolisib to outcomes. (PubMed, Front Immunol) - "Based on currently available data on leniolisib therapy, mortality and several patient-relevant morbidity endpoints are expected to improve in future clinical practice in Germany. Leniolisib may significantly modify the course of disease in APDS patients."

Journal • Bronchiectasis • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases • Transplantation

Treating hematologic immune dysregulation in inborn errors of immunity: a real-life multicenter study. (PubMed, Front Immunol) - "LTT included sirolimus (42.9%), mycophenolate mofetil (34.5%), rituximab (29.8%), and targeted therapies (17.9%)...Response rates are variable and influenced by the underlying diagnosis. Targeted therapies are associated with an improved response, the suboptimal molecular diagnosis rate currently limits their use."

Clinical • Journal • Retrospective data • Bone Marrow Transplantation • Hematological Disorders • Hemophagocytic lymphohistiocytosis • Immunology • Primary Immunodeficiency • Rare Diseases • Transplantation

Pediatric Patients Aged 1 to 6 Years With APDS (clinicaltrials.gov) - P3 | N=16 | Active, not recruiting | Sponsor: Pharming Technologies B.V. | Trial completion date: Oct 2026 ➔ Oct 2028 | Trial primary completion date: Jul 2026 ➔ Jul 2028

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

Pharming announces U.S. FDA acceptance of sNDA resubmission for Joenja (leniolisib) to treat children aged 4 to 11 years with APDS (The Manila Times) - "Following the Complete Response Letter (CRL) received on January 30, 2026, and a subsequent Type A meeting with the FDA on March 26, 2026, the resubmission seeks approval of 40 mg and 50 mg twice-daily dosing for pediatric patients weighing 27 kg or more, who represent a meaningful proportion of the identified pediatric patient population. The resubmission includes additional data requested by the FDA on analytical methods used for production batch testing. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of October 24, 2026...A separate sNDA seeking approval for lower doses for patients weighing less than 27 kg is planned for this summer."

FDA filing • PDUFA • Immunology • Primary Immunodeficiency

Evaluating the impact of leniolisib treatment on symptoms and health-related quality of life in activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome. (PubMed, Front Immunol) - P2/3 | "As data were unsolicited and baseline symptoms/HRQoL were not available, results may not represent all changes experienced, and is not possible to determine the amount of change in symptoms/HRQoL associated with leniolisib. Nevertheless, these analyses indicate that participants with APDS experienced improvements in symptoms and overall wellbeing following treatment with leniolisib."

Clinical • HEOR • Journal • Fatigue • PIK3CD

Expanding the scope of PI3K-δ inhibition: Leniolisib treatment in PRKCD deficiency. (PubMed, J Hum Immun) - "This experience supports expanding Leniolisib's potential indications to appropriately selected patients and conditions. Broader repurposing strategies for targeted therapies in diseases involving dysregulated PI3K signaling should be systematically evaluated in clinical trials."

Journal • Hematological Disorders • Interstitial Lung Disease • Pulmonary Disease • Respiratory Diseases • mTOR • PIK3CD

European Commission grants marketing authorization to Pharming’s Joenja (leniolisib) – the first approved treatment for APDS in the European Union (GlobeNewswire) - "The first European launch is expected in Germany in Q3 2026, with additional launches anticipated pending completion of national reimbursement negotiations....The EC approval is based on results from a multinational, triple-blind, placebo-controlled, randomized Phase II/III clinical trial, evaluating leniolisib in 31 patients with APDS aged 12 years and older."

EMA approval • Launch Europe • Immunology • Primary Immunodeficiency

Interim Safety and Efficacy Outcomes of an Open-Label Long-Term Extension Study of Treatment with PI3Kδ Inhibitor Leniolisib in Pediatric Patients Aged 4-11 Years with Activated PI3Kδ Syndrome (APDS) (CIS 2026) - P3 | "Data are consistent with prior studies in adolescents and adults. Tabular data are included as downloadable supplement files."

Clinical • Musculoskeletal Diseases • Orthopedics • Pediatrics • CD20 • CD27 • PIK3CD

Caregiver- and Clinician-Reported Symptoms in Pediatric Patients with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Receiving Leniolisib (CIS 2026) - P3 | "These findings demonstrated durable and clinically relevant progressive symptom improvement through 12 months. Tabular data are included as downloadable supplement files."

Clinical • Pediatrics • Rare Diseases

NFKB1 Truncating Variants Associated with Significant Autoimmunity and Lymphoproliferation in Common Variable Immunodeficiency (CIS 2026) - P, P2 | "Further elucidation of the mechanisms underlying profound immune dysregulation is crucial because these patients may benefit from the PI3Kδ inhibitor leniolisib, given the observed PI3K signaling activation. A prospective clinical trial is currently recruiting such participants to investigate this targeted therapy (NCT06549114)."

Bone Marrow Transplantation • Primary Immunodeficiency • NFKBIA • PIK3CD

Clinical Experience with Use of the PI3Kdelta Inhibitor Leniolisib to Treat Immune Dysregulation in Patients with CVID and CVID-Like Disorders (CIS 2026) - "Conclusions Experience suggests that PI3K inhibition may offer clinical benefit to CVID and other primary immunodeficiency patients suffering from complications of immune dysregulation. Two phase 2 clinical trials to formally evaluate safety and tolerability in CVID and other patients with clinical manifestations of immune dysregulation are underway in the USA, England, and Spain."

Clinical • Diabetes • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Immunology • Interstitial Lung Disease • Neutropenia • Primary Immunodeficiency • Pulmonary Disease • Respiratory Diseases

Symptom Changes in Pediatric Patients with Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS) Receiving Leniolisib (CIS 2026) - P3 | "Conclusion According to caregiver ratings, the most severe APDS-related symptoms experienced by pediatric patients aged 4–11 years showed improvements after 12 weeks of leniolisib treatment. These results demonstrate the potential clinical benefit of leniolisib in most pediatric patients."

Clinical • Infectious Disease • Pediatrics • Rare Diseases

Pediatric and Adolescent Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS): Demographic and Clinical Findings from the APDS-Characterization and Clinical Outcomes Immunologic Registry (APDS-CHOIR) (CIS 2026) - "Sirolimus was used by six participants (43%) and leniolisib by one participant (7%). Given the paucity of clinical information regarding APDS in this population, these findings may improve the characterization of disease presentation and progression in children and adolescents. Tabular data are included as downloadable supplement files."

Clinical • Clinical data • Bone Marrow Transplantation • Infectious Disease • Pediatrics • PIK3CD • PIK3R1

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: Dec 2025 ➔ Dec 2026 | Trial primary completion date: Oct 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Pediatrics

Shrinking spleens and nodes, expanding horizons: leniolisib and the future of activated phosphoinositide 3-kinase delta syndrome (APDS). (PubMed, J Allergy Clin Immunol Pract) - "Early therapeutic strategies extrapolated from autoimmune lymphoproliferative syndrome, including mTOR inhibition with sirolimus, provided variable control of lymphoproliferation. We summarize current clinical evidence and practical considerations for dosing and monitoring in the absence of serum drug-level assays. Finally, we outline key unresolved questions, including long-term disease modification, biomarker validation, pediatric outcomes, treatment sequencing and combination strategies, while positioning leniolisib relative to hematopoietic stem cell transplantation, and desirability of it's wider global access."

Journal • Bone Marrow Transplantation • Immunology • Pediatrics • Transplantation • PIK3CD

Selective phosphoinositide 3-kinase inhibitors and implication in diabetic retinopathy as pharmacological tools. (PubMed, Front Pharmacol) - "Interestingly, leniolisib, a selective PI3Kδ kinase inhibitor, has been approved for the rare disease Activated Phosphoinositide 3-kinase Delta Syndrome (APDS)...We hereby explored the implication of PI3K signaling in diabetic retinopathy. Moreover, we reviewed the current literature to highlight molecular features of class I PI3K selective inhibitors, to further guide the design of novel selective and safe drugs targeting PI3Kδ, for management of diabetic retinopathy or other retinal proliferative diseases."

Journal • Review • Diabetes • Diabetic Retinopathy • Hematological Malignancies • Lymphoma • Metabolic Disorders • Oncology • Rare Diseases • Retinal Disorders • PIK3CD

Pharming Group announces approval of Joenja (leniolisib) in Japan for the treatment of APDS in patients aged 4 years and older (PRNewswire) - "Approval is based on positive Phase III data from multinational and Japanese studies in patients aged 12 years and older and a multinational pediatric study in children aged 4 to 11 years...The launch of Joenja is expected following agreement with the MHLW on its National Health Insurance drug price."

Japan approval • Primary Immunodeficiency

Pharming Group receives positive CHMP opinion for Joenja (leniolisib) for the treatment of APDS in adult and pediatric patients 12 years and older (The Manila Times) - "Decision based on Phase II/III clinical data demonstrating statistically significant impact on measures of immune dysregulation and immunodeficiency. Final European Commission decision expected in Q2 2026....The centralized marketing authorization would be valid in all 27 European Union Member States, as well as Norway, Iceland and Liechtenstein."

CHMP • EMA approval • Primary Immunodeficiency

LE 8201: Leniolisib for immune dysregulation in CVID (clinicaltrialsregister.eu) - P1/2 | N=6 | Active, not recruiting | Sponsor: Pharming Technologies B.V. | Recruiting ➔ Active, not recruiting

Enrollment closed • Primary Immunodeficiency • CARD11 • CD20 • CD81 • CTLA4 • CTNNB1 • IKZF1 • NFKB2 • PTEN • SEC61A1 • TNFRSF13B • TNFRSF13C • TNFSF12