pharma · Prurigo Nodularis · Vitiligo
Incyte is a pharma organization headquartered in Wilmington, USA. Primary therapeutic focus areas include Prurigo Nodularis, Vitiligo, Hidradenitis Suppurativa, Chronic Graft-Versus-Host Disease, chronic graft-versus-hos
Phase 2 · small molecule · Lymphoma
Parsaclisib (INCB 50465-203) is a small-molecule PI3-kinase p110-delta subunit inhibitor developed by Incyte for the treatment of lymphoma. The drug targets the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, a key signaling pathway implicated in B-cell malignancies. The CITADEL-203 phas
Internal code INCB 50465-203 (CITADEL-203)
Parsaclisib (INCB 50465-203) is a small-molecule PI3-kinase p110-delta subunit inhibitor developed by Incyte for the treatment of lymphoma. The drug targets the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, a key signaling pathway implicated in B-cell malignancies. The CITADEL-203 phase 2 trial (NCT03126019) evaluated parsaclisib in lymphoma patients and has been completed as of March 2025. However, Incyte's regulatory strategy encountered a setback in Europe, where an EMA marketing authorization application was withdrawn, indicating the sponsor chose not to pursue or could not sustain approval in that region. The drug remains in development phase 2 status globally, with no current approved indication disclosed. The mechanism of action as a selective PI3K delta inhibitor positions parsaclisib within the immunomodulatory oncology space, where such agents have demonstrated clinical utility in hematologic malignancies. The completed CITADEL-203 trial represents a key milestone, though detailed efficacy and safety data have not yet been disclosed in the facts provided. Incyte's decision to withdraw the EMA application suggests either strategic reprioritization or challenges in meeting regulatory approval criteria.
PI3K delta inhibitors represent an important therapeutic class for B-cell lymphomas, where dysregulation of PI3K signaling drives malignant proliferation and survival. The unmet medical need in lymphoma remains substantial, particularly for patients with relapsed or refractory disease and those seeking alternatives to conventional chemotherapy or established targeted agents. Parsaclisib's selective targeting of the delta isoform may offer a differentiated safety and efficacy profile compared to pan-PI3K inhibitors, potentially reducing toxicity to other cell types while maintaining anti-tumor activity in B cells.
The competitive landscape for lymphoma therapeutics includes multiple approved agents across different mechanisms, including proteasome inhibitors (KYPROLIS), tyrosine kinase inhibitors (ALUNBRIG, INLYTA), and tubulin inhibitors (CABAZITAXEL ACCORD). However, the specific niche of selective PI3K delta inhibition in lymphoma represents a distinct therapeutic approach. The withdrawal of the EMA application raises questions about commercial viability or regulatory feasibility in key markets, potentially limiting Incyte's near-term commercial opportunity. The patient population for lymphoma is substantial, but market access and reimbursement dynamics vary significantly by geography and disease subtype. The completed phase 2 trial and subsequent regulatory decision suggest Incyte is reassessing the program's development strategy, with unclear implications for future advancement or potential partnership opportunities.
Drug Class: Antineoplastic and immunomodulating agent (ATC L01)
Mechanism of Action: Selective inhibitor of phosphatidylinositol 3-kinase (PI3K) p110-delta subunit
Molecular Target: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD)
Modality: Small-molecule oral or systemic agent (route of administration not yet disclosed)
Therapeutic Rationale: The PI3K/AKT/mTOR pathway is frequently hyperactivated in B-cell lymphomas through PIK3CD mutations or amplification. Selective delta isoform inhibition preferentially affects B cells and T cells while sparing other cell types, potentially improving the therapeutic window compared to pan-PI3K inhibitors.
Related Therapies: Other PI3K inhibitors in development or approved for hematologic malignancies; BTK inhibitors (ibrutinib, acalabrutinib); mTOR inhibitors; proteasome inhibitors; and conventional chemotherapy regimens.
Regulatory Classification: Incyte Biosciences Distribution B.V. holds the EMA product number EMEA/H/C/005893; the application was withdrawn, indicating no current European marketing authorization.
Also known as: lymphoma (Hodgkin and non-Hodgkin), lymphoma (Hodgkin's and non-Hodgkin's), lymphoma, malignant, lymphomatous, malignant lymphoma, MLYM
A malignant (clonal) proliferation of B- lymphocytes or T- lymphocytes which involves the lymph nodes, bone marrow and/or extranodal sites. This category includes Non-Hodgkin lymphomas and Hodgkin lymphomas.
ClinicalTrials.gov lists 16 registered studies for Lymphoma, Hodgkin (AACT aggregate).
Phase breakdown: NA (10), PHASE1 (3), PHASE2 (3)
Common investigational therapies:
Disease data sourced from MONDO Disease Ontology (MONDO:0005062), Orphanet — lymphoma, NCT00026208, NCT00578461, NCT01459224, NCT02996773, NCT03117036, AACT (ClinicalTrials.gov aggregate), ClinicalTrials.gov, Open Targets Platform (CC BY 4.0).
CITADEL-203 trial enrollment and conduct
Phase 2 study (NCT03126019) evaluating parsaclisib in lymphoma patients was conducted under Incyte sponsorship.
CITADEL-203 trial completed
Phase 2 trial completion milestone reached; detailed results and regulatory implications not yet disclosed.
EMA application withdrawn
Incyte withdrew the European marketing authorization application for parsaclisib (EMEA/H/C/005893), indicating no pursuit of EMA approval at this time.
The lymphoma therapeutics market includes multiple approved agents with diverse mechanisms. KYPROLIS (carfilzomib, Amgen) is a 26S proteasome inhibitor approved for multiple myeloma and certain lymphomas. ALUNBRIG (brigatinib, Lacuna Pharma) is an ALK tyrosine kinase inhibitor used in ALK-positive malignancies. INLYTA (axitinib, Pfizer) targets vascular endothelial growth factor receptors. MEKTOVI (binimetinib, Pierre Fabre) inhibits dual specificity mitogen-activated protein kinase kinase 1. CABAZITAXEL ACCORD (Lacuna Pharma) and CABOMETYX (cabozantinib, Ipsen) represent tubulin and hepatocyte growth factor receptor inhibition, respectively. EVOLTRA (clofarabine, Amneal Pharma) is a DNA polymerase inhibitor. These agents collectively address multiple lymphoma subtypes and resistance mechanisms, but none specifically target PI3K delta as a primary indication in the disclosed facts.
Parsaclisib's selective PI3K delta inhibition represents a mechanistically distinct approach, potentially offering advantages in B-cell lymphomas where delta isoform activation is prevalent. However, the withdrawal of the EMA application suggests Incyte encountered either regulatory challenges, insufficient efficacy/safety data, or strategic reprioritization. The competitive positioning remains unclear pending disclosure of CITADEL-203 results and Incyte's future development strategy.
| Therapy | Company | Mechanism | Status |
|---|---|---|---|
| GLIADEL | Eisai Co., | Glutathione reductase inhibitor | approved |
| TEKINEX | Teva Pharma GmbH | Protein synthesis inhibitor | approved |
| ALUNBRIG | Lacuna Pharma Pty Ltd | ALK tyrosine kinase receptor inhibitor | approved |
| KYPROLIS | Amgen | 26S proteosome inhibitor | approved |
| EVOLTRA | Amneal Pharma Europe Ltd | DNA polymerase (alpha/delta/epsilon) inhibitor | approved |
| APX-CELECOXIB | Viatris Pharmaceuticals Co., | Cyclooxygenase-2 inhibitor | approved |
| INLYTA | Pfizer Australia Pty Ltd | Vascular endothelial growth factor receptor inhibitor | approved |
| MEKTOVI | Pierre Fabre Australia Pty Ltd | Dual specificity mitogen-activated protein kinase kinase 1 inhibitor | approved |
| CABAZITAXEL ACCORD | Lacuna Pharma Pty Ltd | Tubulin inhibitor | approved |
| CABOMETYX | Ipsen | Hepatocyte growth factor receptor inhibitor | approved |
| CAPECITABINE SANDOZ | Alphapharm Pty Ltd | Thymidylate synthase inhibitor | approved |
| UNITUXIN | United Therapeutics Europe Ltd | Disialoganglioside GD2 binding agent | approved |
| ZOLEDRONIC ACID | — | Farnesyl diphosphate synthase inhibitor | Approved |
| ZANUBRUTINIB | — | Tyrosine-protein kinase BTK inhibitor | Approved |
| VORINOSTAT | — | Histone deacetylase 1 inhibitor | Approved |
| VINBLASTINE SULFATE | — | Tubulin inhibitor | Approved |
| VENETOCLAX | — | Apoptosis regulator Bcl-2 inhibitor | Approved |
| UMBRALISIB TOSYLATE | — | Tyrosine-protein kinase ABL inhibitor | Approved |
| TISAGENLECLEUCEL | — | B-lymphocyte antigen CD19 binding agent | Approved |
| THALIDOMIDE | — | CRL4(CRBN) E3 ubiquitin ligase inhibitor | Approved |
Additional associated therapies sourced from Open Targets Platform (CC0), linked to NovaPharmaNews drug profiles where matched.
European Medicines Agency (EMA): Incyte Biosciences Distribution B.V. submitted a marketing authorization application for parsaclisib (EMEA/H/C/005893). The application was subsequently withdrawn, indicating Incyte did not pursue or could not sustain approval in the European Union. No authorization date is recorded.
U.S. Food and Drug Administration (FDA): Regulatory status with the FDA is not yet disclosed in the available facts.
Japan (PMDA) and China (NMPA): Regulatory status in these jurisdictions is not yet disclosed.
Clinical Trial Transparency: The pivotal trial NCT03126019 (CITADEL-203) has been completed as of March 2025, but detailed trial results, regulatory submissions, or approval decisions have not been disclosed. The withdrawal of the EMA application occurred at an undisclosed date and may reflect trial outcomes, safety signals, or strategic decisions by Incyte.
Parsaclisib is a small-molecule PI3K delta inhibitor in development for the treatment of lymphoma. It has not yet received regulatory approval for any indication.
Parsaclisib selectively inhibits the phosphatidylinositol 3-kinase (PI3K) p110-delta subunit, targeting the PIK3CD gene product. This mechanism preferentially affects B cells and T cells, disrupting pro-survival signaling in lymphoma cells.
Parsaclisib is developed and sponsored by Incyte Corporation. The EMA marketing authorization holder would be Incyte Biosciences Distribution B.V., though the application was withdrawn.
Regulatory status with the FDA is not yet disclosed. The drug remains in phase 2 development globally.
No. Incyte withdrew the European marketing authorization application (EMEA/H/C/005893), indicating parsaclisib is not approved by the EMA.
The CITADEL-203 trial (NCT03126019) is a phase 2 study evaluating parsaclisib in lymphoma patients. The trial was completed as of March 2025, but detailed results have not yet been disclosed.
Parsaclisib is in phase 2 development. The CITADEL-203 trial has been completed, but the program's future direction is unclear following the withdrawal of the EMA application.
Parsaclisib is classified as an antineoplastic and immunomodulating agent (ATC L01) and specifically as a PI3K delta inhibitor.
Parsaclisib targets the phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (PIK3CD), the gene encoding the p110-delta subunit of PI3K.
The specific lymphoma subtypes evaluated in CITADEL-203 are not yet disclosed. PI3K delta inhibitors are generally relevant to B-cell lymphomas where delta isoform activation occurs.
The specific reason for withdrawal is not disclosed. Possible factors include insufficient efficacy or safety data, regulatory feedback, or strategic reprioritization by Incyte.
Competing agents include KYPROLIS (proteasome inhibitor), ALUNBRIG (ALK inhibitor), INLYTA (VEGFR inhibitor), MEKTOVI (MEK inhibitor), CABAZITAXEL ACCORD (tubulin inhibitor), CABOMETYX (HGF receptor inhibitor), EVOLTRA (DNA polymerase inhibitor), and others with diverse mechanisms.
Parsaclisib is a small-molecule drug, not a biologic.
The route of administration (oral, intravenous, etc.) has not yet been disclosed in the available facts.
No partner is disclosed for parsaclisib. Incyte is the sole sponsor of the program.
The timing of CITADEL-203 results publication is not yet disclosed. Results may be presented at medical conferences or published in peer-reviewed journals.
Projected peak sales and commercial forecasts are not yet disclosed. The withdrawal of the EMA application raises questions about near-term commercial viability.
Parsaclisib → Drug → Target → Indication → Company → Trials → Competitors
Strategic Implications: The completion of CITADEL-203 followed by withdrawal of the EMA application suggests Incyte is reassessing parsaclisib's development trajectory. The lack of disclosed trial results and the regulatory withdrawal raise questions about efficacy, safety, or commercial viability in key markets. Incyte may be considering alternative development pathways, such as focusing on specific lymphoma subtypes, exploring combination strategies, or pursuing partnerships.
Competitive Implications: The PI3K delta inhibitor space for lymphoma remains competitive but not saturated. Withdrawal of parsaclisib from EMA consideration may reduce competitive pressure in Europe but also signals potential challenges in the mechanism class or indication. Other PI3K delta inhibitors in development by competitors may benefit from reduced competition if parsaclisib is deprioritized.
Future Catalysts: Key milestones include disclosure of CITADEL-203 efficacy and safety data, clarification of Incyte's future development strategy (continuation, partnership, or discontinuation), potential FDA submissions or interactions, and any label expansion or combination therapy trials. The timing and nature of these disclosures will be critical for assessing parsaclisib's long-term viability.
Expected Milestones: Pending publication of CITADEL-203 results; potential FDA pre-clinical meeting or IND application; partnership announcements; or formal discontinuation notice. No expected next milestone date is currently disclosed.
Concise, citable answers optimized for AI answer engines.
Intelligence compiled from public regulatory and clinical sources (FDA, EMA, ClinicalTrials.gov and company disclosures). Figures may be editorial or analyst estimates; verify against primary sources before relying on them.