Umbralisib

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Umbralisib
Umbralisib.svg
Clinical data
Trade namesUkoniq
Other namesRP5264; TGR-1202
AHFS/Drugs.comUkoniq
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
  • 2-[(1S)-1-[4-Amino-3-(3-fluoro-4-propan-2-yloxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-6-fluoro-3-(3-fluorophenyl)chromen-4-one
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC31H24F3N5O3
Molar mass571.560 g·mol−1
3D model (JSmol)
  • CC(C)OC1=C(C=C(C=C1)C2=NN(C3=NC=NC(=C23)N)C(C)C4=C(C(=O)C5=C(O4)C=CC(=C5)F)C6=CC(=CC=C6)F)F
  • InChI=1S/C31H24F3N5O3/c1-15(2)41-24-9-7-18(12-22(24)34)27-26-30(35)36-14-37-31(26)39(38-27)16(3)29-25(17-5-4-6-19(32)11-17)28(40)21-13-20(33)8-10-23(21)42-29/h4-16H,1-3H3,(H2,35,36,37)/t16-/m0/s1
  • Key:IUVCFHHAEHNCFT-INIZCTEOSA-N

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]

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 is a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon.[2][3][4] Umbralisib was approved for medical use in the United States in February 2021.[2][5][6]

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).[7][8] Three year data (including follicular lymphoma and DLBCL) was announced June 2016.[9] It is in combination trials for various leukemias and lymphomas, such as mantle cell lymphoma (MCL)[10][11] and other lymphomas.[12]

Umbralisib was granted breakthrough therapy designation 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.[13]

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][14][15][16][17]

References[]

  1. ^ a b c d e f "Ukoniq- umbralisib tablet, film coated". DailyMed. Retrieved 13 September 2021.
  2. ^ a b c d e f g h i j "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. Public Domain 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. ^ "Drug Approval Package: Ukoniq (umbralisib)". U.S. Food and Drug Administration (FDA). 5 March 2020. Retrieved 13 September 2021.
  7. ^ Inman S (19 March 2016). "Novel BTK, PI3K Inhibitors on Horizon for Relapsed CLL". OncLive. Archived from the original on 1 May 2016.
  8. ^ "Therapy Focus –- TG Could Benefit From Zydelig Setback". Seeking Alpha. 29 March 2016.
  9. ^ "TG Therapeutics, Inc. Announces First Patient Enrolled in the Registration-Directed UNITY-DLBCL Phase 2b Trial". TG Therapeutics Inc. June 2016.
  10. ^ 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
  11. ^ "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.
  12. ^ 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
  13. ^ Columbus G (22 January 2019). "FDA Grants Umbralisib Breakthrough Designation for Marginal Zone Lymphoma". OncLive. Archived from the original on 23 January 2019.
  14. ^ "Orphan Treatment of extranodal marginal zone lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  15. ^ "Orphan Treatment of splenic marginal zone lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  16. ^ "Orphan Treatment of Follicular Lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.
  17. ^ "Orphan Treatment of nodal marginal zone lymphoma". U.S. Food and Drug Administration (FDA). 11 April 2019. Retrieved 5 February 2021.

External links[]

  • "Umbralisib". Drug Information Portal. U.S. National Library of Medicine.
  • "Umbralisib". NCI Drug Dictionary. National Cancer Institute.


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