Umbralisib

Umbralisib, sold under the brand name Ukoniq, is a medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL).[2] It is taken by mouth.[2]

Umbralisib
Clinical data
Trade namesUkoniq
Other namesRP5264; TGR-1202
License data
Pregnancy
category
  • Not recommended[1]
Routes of
administration		By mouth
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
MetabolismCYP2C9, CYP3A4, and CYP1A2[1]
Elimination half-life91 h[1]
ExcretionFeces, urine[1]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC31H24F3N5O3
Molar mass571.560 g·mol−1
3D model (JSmol)

The most common side effects include increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash.[2]

Umbralisib inhibits P110δ and casein kinase CK1-epsilon.[2][3][4] Umbralisib was approved for medical use in the United States in February 2021.[2][5]

Medical uses

Umbralisib is indicated for adults with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen; and adults with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.[2][1]

Adverse effects

The prescribing information provides warnings and precautions for adverse reactions including infections, neutropenia, diarrhea and non-infectious colitis, hepatotoxicity, and severe cutaneous reactions.[2]

History

It has undergone clinical studies for chronic lymphocytic leukemia (CLL).[6][7] Three year data (including follicular lymphoma and DLBCL) was announced June 2016.[8] It is in combination trials for various leukemias and lymphomas, such as mantle cell lymphoma (MCL)[9][10] and other lymphomas.[11]

Umbralisib was granted breakthrough therapy desgination by the U.S. Food and Drug Administration (FDA) for use in people with marginal zone lymphoma (MZL), a type of cancer with no specifically approved therapies.[12]

FDA approval was based on two single-arm cohorts of an open-label, multi-center, multi-cohort trial, UTX-TGR-205 (NCT02793583), in 69 participants with marginal zone lymphoma (MZL) who received at least one prior therapy, including an anti-CD20 containing regimen, and in 117 participants with follicular lymphoma (FL) after at least two prior systemic therapies.[2] The application for umbralisib was granted priority review for the marginal zone lymphoma (MZL) indication and orphan drug designation for the treatment of MZL and follicular lymphoma (FL).[2][13][14][15][16]

References
  1. "Ukoniq (umbralisib) tablets, for oral use" (PDF). TG Therapeutics.
  2. "FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular lymphoma". U.S. Food and Drug Administration (FDA). 5 February 2021. Retrieved 5 February 2021. This article incorporates text from this source, which is in the public domain.
  3. Lunning M, Vose J, Nastoupil L, Fowler N, Burger JA, Wierda WG, et al. (November 2019). "Ublituximab and umbralisib in relapsed/refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia". Blood. 134 (21): 1811–20. doi:10.1182/blood.2019002118. PMC 7042665. PMID 31558467.
  4. Burris HA, Flinn IW, Patel MR, Fenske TS, Deng C, Brander DM, et al. (April 2018). "Umbralisib, a novel PI3Kδ and casein kinase-1ε inhibitor, in relapsed or refractory chronic lymphocytic leukaemia and lymphoma: an open-label, phase 1, dose-escalation, first-in-human study". Lancet Oncology. 19 (4): 486–96. doi:10.1016/S1470-2045(18)30082-2. PMID 29475723.
  5. "TG Therapeutics Announces FDA Accelerated Approval of Ukoniq (umbralisib)" (Press release). TG Therapeutics. 5 February 2021. Retrieved 5 February 2021 – via GlobeNewswire.
  6. Inman S (19 March 2016). "Novel BTK, PI3K Inhibitors on Horizon for Relapsed CLL". OncLive. Archived from the original on 1 May 2016.
  7. "Therapy Focus –- TG Could Benefit From Zydelig Setback". Seeking Alpha. 29 March 2016.
  8. "TG Therapeutics, Inc. Announces First Patient Enrolled in the Registration-Directed UNITY-DLBCL Phase 2b Trial". TG Therapeutics Inc. June 2016.
  9. Clinical trial number NCT02268851 for "A Phase I/Ib Safety and Efficacy Study of the PI3K-delta Inhibitor TGR-1202 and Ibrutinib in Patients With CLL or MCL" at ClinicalTrials.gov
  10. "Follow-Up Data for Combination of TGR-1202 (umbralisib) plus Ibrutinib in Patients with Relapsed or Refractory CLL and MCL" (Press release). TG Therapeutics. 14 June 2017 – via Globenewswire.
  11. Clinical trial number NCT02793583 for "Study to Assess the Efficacy and Safety of Ublituximab + TGR-1202 With or Without Bendamustine and TGR-1202 Alone in Patients With Previously Treated Non-Hodgkin's Lymphoma (UNITY-NHL)" at ClinicalTrials.gov
  12. Columbus G (22 January 2019). "FDA Grants Umbralisib Breakthrough Designation for Marginal Zone Lymphoma". OncLive. Archived from the original on 23 January 2019.
  13. "Orphan Treatment of extranodal marginal zone lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  14. "Orphan Treatment of splenic marginal zone lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  15. "Orphan Treatment of Follicular Lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  16. "Orphan Treatment of nodal marginal zone lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  • "Umbralisib". Drug Information Portal. U.S. National Library of Medicine.
  • "Umbralisib". NCI Drug Dictionary. National Cancer Institute.


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