Leniolisib

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome.

• JOENJA is indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older. JOENJA is a kinase inhibitor indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older.

• None. None.contraindicated

Verify pregnancy status in females of reproductive potential prior to initiating treatment. ( 2.1 , 5.1 ) Recommended dosage: 70 mg administered orally twice daily approximately 12 hours apart, with or without food, in adult and pediatric patients 12 years of age and older and weighing ≥ 45kg. ( 2.2 ) 2.1 Testing Prior to Treatment with JOENJA Verify pregnancy status in females of reproductive potential prior to initiating treatment with JOENJA [see Warnings and Precautions ( 5.1 ), and Use in Specific Populations ( 8.1 , 8.3 )] . 2.2 Recommended Dosage and Administration The recommended dosage of JOENJA in adult and pediatric patients 12 years of age and older weighing 45 kg or greater is 70 mg administered orally twice daily approximately 12 hours apart, with or without food. There is no recommended dosage for patients weighing less than 45 kg. Advise patients that if a dose is missed by more than 6 hours, wait and take the next dose at the usual time. Advise patients that if vomiting occurs within 1 hour after taking JOENJA, take JOENJA as soon as possible. If vomiting occurs more than 1 hour after dosing, wait and take the next dose at the usual time.

Embryo-Fetal Toxicity: JOENJA may cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. ( 5.1 , 8.1 , 8.3 ) Vaccinations: Live, attenuated vaccinations may be less effective if administered during JOENJA treatment. ( 5.2 ) Risk of Hypersensitivty Reactions Including Anaphylaxis: Hypersensitivity reactions including anaphlyaxis have been reported in the postmarketing setting. If hypersensitivity reactions occur, discontinue JOENJA and institute appropriate therapy. ( 5.3 ) 5.1 Embryo-Fetal Toxicity Based on findings in animals, JOENJA may cause fetal harm when administered to a pregnant woman. Administration of leniolisib to rats and rabbits during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 2-6 times higher than the maximum recommended human dose (MRHD) in APDS patients based on AUC comparisons. Verify the pregnancy status of patients of reproductive potential prior to starting treatment. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use highly effective methods of contraception during treatment and for 1 week after the last dose [see Dosage and Administration ( 2.1 ), Use in Specific Populations ( 8.1 , 8.3 )] . 5.2 Vaccinations Live, attenuated vaccinations may be less effective if administered during JOENJA treatment. 5.3 Risk of Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reaction(s), including anaphylaxis, have been reported in postmarketing setting.

The following clinically significant adverse reactions are described elsewhere in the labeling: Risk of Hypersensitivity Reactions, Including Anaphylaxis [see Warnings and Precautions (5.3) ] Most common adverse reactions (incidence > 10%) were headache, sinusitis, and atopic dermatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Pharming Healthcare Inc. at 1-800-930-5221 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of JOENJA reflects exposure based on 38 adult and pediatric patients 12 years of age and older with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) from the placebo-controlled portion of Study 2201 [see Clinical Studies ( 14 )] and additional open-label clinical safety data. Thirty-seven of 38 patients received JOENJA 70 mg orally twice daily for at least 25 weeks and 66% were exposed for 96 weeks or longer. Median duration of JOENJA treatment was approximately 2 years, and 4 patients had more than 5 years of JOENJA exposure. The data below are based on the 12-week, placebo-controlled portion of Study 2201 in which either JOENJA 70 mg (N=21) or placebo (N=10) was administered twice daily to patients with APDS.

Lactation: Advise women not to breastfeed. ( 8.2 ) Hepatic impairment: Use in patients with moderate to severe hepatic impairment is not recommended. ( 8.6 ) 8.1 Pregnancy Risk Summary JOENJA can cause fetal harm based on findings from animal studies. There are no available data on JOENJA use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of leniolisib to pregnant rats and rabbits during the period of organogenesis at exposures approximately 2-6 times the MRHD on an AUC basis, produced embryofetal toxicity including malformations ( see Data ). Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage of clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Leniolisib was administered orally to pregnant rats at doses of 10, 30, and 120 mg/kg/day during the period of organogenesis from gestation Day 6 to Day 17.

Metabolism

The systemic drug exposure (AUC and C max ) of leniolisib increased dose proportionally within the studied range of doses (20 to 140 mg twice a day dosing and single doses of 10 to 400 mg). During twice daily dosing approximately 12 hours apart, leniolisib accumulates approximately 1.4-fold (range of 1.0 to 2.2) in achieving steady-state, consistent with an effective half-life (t 1/2 ) of approximately 7 hours.

If overdosage occurs, monitor the patient for any signs or symptoms of adverse reactions. Treatment of overdose with JOENJA consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.

• Mar 24, 2023NDANDA217759Pharming

1. 1Infection12116%
2. 2Product Dose Omission Issue10715%
3. 3Off Label Use567.6%
4. 4Sinusitis435.8%
5. 5Headache385.2%
6. 6Nasopharyngitis364.9%
7. 7Fatigue253.4%
8. 8Ear Infection243.3%
9. 9Nausea243.3%
10. 10Alopecia212.9%
11. 11Pneumonia212.9%
12. 12Diarrhoea202.7%
13. 13Cough172.3%
14. 14Vomiting172.3%
15. 15Rash152.0%

The 10 most recently updated of 10 ClinicalTrials.gov registrations naming Leniolisib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Pediatric Patients Aged 4 to 11 Years With APDS
  Active not recruiting · Phase 3 · Interventional · 15 enrolled · Pharming Technologies B.V.
  NCT05438407updated 2026-05-06
• Extension to the Study of Efficacy of CDZ173 in Patients With APDS/PASLI
  Terminated · Phase 2 · Phase 3 · Interventional · 37 enrolled · Pharming Technologies B.V.
  NCT02859727updated 2026-03-30
• New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome
  Recruiting · Observational · 14 enrolled · Assistance Publique - Hôpitaux de Paris
  NCT06694363updated 2026-03-23
• Leniolisib for Immune Dysregulation in PIDs
  Active not recruiting · Phase 2 · Interventional · 12 enrolled · Pharming Technologies B.V.
  NCT06549114updated 2026-02-13
• Long-term Safety and Efficacy of Leniolisib in PIDs With Immune Dysregulation
  Recruiting · Phase 2 · Interventional · 12 enrolled · Pharming Technologies B.V.
  NCT06990529updated 2026-02-13
• Leniolisib for Immune Dysregulation in CVID
  Active not recruiting · Phase 2 · Interventional · 20 enrolled · Pharming Technologies B.V.
  NCT06897358updated 2026-02-12
• Pediatric Patients Aged 1 to 6 Years With APDS
  Active not recruiting · Phase 3 · Interventional · 16 enrolled · Pharming Technologies B.V.
  NCT05693129updated 2025-10-28
• An Open-Label Study to Assess the Safety & Efficacy of Leniolisib in Japanese Patients With APDS
  Unknown · Phase 3 · Interventional · 3 enrolled · Pharming Technologies B.V.
  NCT06249997updated 2024-02-08
• Study of Efficacy of CDZ173 in Patients With APDS/PASLI
  Completed · Phase 2 · Phase 3 · Interventional · 37 enrolled · Novartis Pharmaceuticals
  NCT02435173updated 2022-08-10
• Safety, Pharmacokinetics, and Preliminary Efficacy Study of CDZ173 in Patients With Primary Sjögren's Syndrome
  Completed · Phase 2 · Interventional · 30 enrolled · Novartis Pharmaceuticals
  NCT02775916updated 2021-01-05

Frequently asked questions

How does Leniolisib work?

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome.

What is Leniolisib used for?

According to FDA labeling, Leniolisib carries indications including: JOENJA is indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older. JOENJA is a kinase inhibitor indicated for the treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Leniolisib?

Leniolisib is classified as Other immunostimulants, Kinase Inhibitor, Breast Cancer Resistance Protein Inhibitors, Cytochrome P450 1A2 Inhibitors, Kinase Inhibitors, Organic Anion Transporting Polypeptide 1B1 Inhibitors, Organic Anion Transporting Polypeptide 1B3 Inhibitors, Phosphoinositide 3-Kinase delta Inhibitors, Cellular Proliferation Alteration, Decreased B Lymphocyte Activation, Decreased T Lymphocyte Activation.

What are the brand names for Leniolisib?

Leniolisib is marketed under brand names including Joenja.

What are the contraindications for Leniolisib?

Leniolisib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.