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Joenja (LENIOLISIB)
Joenja works by blocking the activity of a specific enzyme called PI3K delta, which is involved in the immune system's response.
At a glance
| Generic name | LENIOLISIB |
|---|---|
| Sponsor | Pharming |
| Target | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform |
| Modality | Small molecule |
| Therapeutic area | Immunology |
| Phase | FDA-approved |
| First approval | 2023 |
Mechanism of action
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. In cell-based assays, leniolisib reduced pAKT pathway activity and inhibited proliferation and activation of and cell subsets. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and to the dysregulation of and cells.
Approved indications
- Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS)
Common side effects
- Headache
- Sinusitis
- Dermatitis atopic
- Tachycardia
- Diarrhea
- Fatigue
- Pyrexia
- Back pain
- Neck pain
- Alopecia
Drug interactions
- Strong CYP3A4 Inhibitors
- Strong and Moderate CYP3A4 Inducers
- BCRP, OATP1B1, and OATP1B3 Substrates
Key clinical trials
- New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome
- Long-term Safety and Efficacy of Leniolisib in PIDs With Immune Dysregulation (PHASE2)
- Leniolisib for Immune Dysregulation in PIDs (PHASE2)
- Leniolisib for Immune Dysregulation in CVID (PHASE2)
- Pediatric Patients Aged 1 to 6 Years With APDS (PHASE3)
- Pediatric Patients Aged 4 to 11 Years With APDS (PHASE3)
- Extension to the Study of Efficacy of CDZ173 in Patients with APDS/PASLI (PHASE2,PHASE3)
- An Open-Label Study to Assess the Safety & Efficacy of Leniolisib in Japanese Patients With APDS (PHASE3)
Patents
| Patent | Expiry | Type |
|---|---|---|
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
| FDA Orange Book | Patents + exclusivity |