Pomalidomide Explained

Verifiedfields:changed
Watchedfields:changed
Verifiedrevid:352895258
Width:200
Chirality:Racemic mixture
Tradename:Pomalyst, Imnovid
Licence Eu:yes
Dailymedid:Pomalidomide
Pregnancy Au:X
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth
Atc Prefix:L04
Atc Suffix:AX06
Legal Au:S4
Legal Au Comment:[2] [3]
Legal Br:C3
Legal Br Comment:[4]
Legal Ca:Rx-only
Legal Ca Comment:[5]
Legal Uk:POM
Legal Uk Comment:[6]
Legal Us:Rx-only
Legal Eu:Rx-only
Bioavailability:73% (at least)[7]
Protein Bound:12–44%
Metabolism:Liver (mostly CYP1A2- and CYP3A4-mediated; some minor contributions by CYP2C19 and CYP2D6)
Elimination Half-Life:7.5 hours
Excretion:Urine (73%), faeces (15%)
Cas Number:19171-19-8
Pubchem:134780
Iuphar Ligand:7348
Drugbank:DB08910
Chemspiderid:118785
Unii:D2UX06XLB5
Kegg:D08976
Chembl:43452
Iupac Name:4-amino-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione
C:13
H:11
N:3
O:4
Smiles:C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)N
Stdinchi:1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)
Stdinchikey:UVSMNLNDYGZFPF-UHFFFAOYSA-N

Pomalidomide, sold under the brand names Pomalyst and Imnovid, is an anti-cancer medication used for the treatment of multiple myeloma and AIDS-related Kaposi sarcoma.[8]

Pomalidomide was approved for medical use in the United States in February 2013,[9] and in the European Union in August 2013. It is available as a generic medication.[10]

Medical uses

In the European Union, pomalidomide, in combination with bortezomib and dexamethasone, is indicated in the treatment of adults with multiple myeloma who have received at least one prior treatment regimen including lenalidomide; and in combination with dexamethasone is indicated in the treatment of adults with relapsed and refractory multiple myeloma who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy.[11]

In the United States, pomalidomide is indicated, in combination with dexamethasone, for people with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy; and is indicated for people with AIDS-related Kaposi sarcoma after failure of highly active antiretroviral therapy (HAART) or in people with Kaposi sarcoma who are HIV-negative.[12] [13] [14] [15]

Origin and development

The parent compound of pomalidomide, thalidomide, was originally discovered to inhibit angiogenesis in 1994.[16] Based upon this discovery, thalidomide was taken into clinical trials for cancer, leading to its ultimate FDA approval for multiple myeloma.[17] Structure-activity studies revealed that amino substituted thalidomide had improved antitumor activity, which was due to its ability to directly inhibit both the tumor cell and vascular compartments of myeloma cancers.[18] This dual activity of pomalidomide makes it more efficacious than thalidomide in vitro and in vivo.[19]

Mechanism of action

Pomalidomide directly inhibits angiogenesis and myeloma cell growth. This dual effect is central to its activity in myeloma, rather than other pathways such as TNF alpha inhibition, since potent TNF inhibitors including rolipram and pentoxifylline do not inhibit myeloma cell growth or angiogenesis.[18] Upregulation of interferon gamma, IL-2 and IL-10 as well as downregulation of IL-6 have been reported for pomalidomide. These changes may contribute to pomalidomide's anti-angiogenic and anti-myeloma activities.

Like thalidomide, pomalidomide works as a cereblon E3 ligase modulator.[20]

Side effects

Pomalidomide can cause harm to unborn babies when administered during pregnancy.

Pomalidomide is present in the semen of people receiving the drug.

Clinical trials

Phase I trial results showed tolerable side effects.[21]

Phase II clinical trials for multiple myeloma and myelofibrosis reported 'promising results'.[22] [23]

Phase III results showed significant extension of progression-free survival, and overall survival (median 11.9 months vs. 7.8 months; p = 0.0002) in patients taking pomalidomide and dexamethasone vs. dexamethasone alone.[24]

Notes and References

  1. Web site: Pomalidomide (Pomalyst) Use During Pregnancy . Drugs.com . 14 May 2020 . 21 September 2020 . 25 January 2021 . https://web.archive.org/web/20210125172209/https://www.drugs.com/pregnancy/pomalidomide.html . live .
  2. Web site: Pomalidomide Medicianz/ Pomalimed/ Pomalidomide Medsurge (Medicianz Healthcare Pty Ltd) . Therapeutic Goods Administration (TGA) . 5 December 2022 . 9 April 2023 . 18 March 2023 . https://web.archive.org/web/20230318044400/https://www.tga.gov.au/resources/prescription-medicines-registrations/pomalidomide-medicianz-pomalimed-pomalidomide-medsurge-medicianz-healthcare-pty-ltd . live .
  3. Web site: Prescription medicines: registration of new chemical entities in Australia, 2014 . Therapeutic Goods Administration (TGA) . 21 June 2022 . 10 April 2023 . 10 April 2023 . https://web.archive.org/web/20230410065838/https://www.tga.gov.au/resources/resource/guidance/prescription-medicines-registration-new-chemical-entities-australia-2014 . live .
  4. Web site: Anvisa . Brazilian Health Regulatory Agency . 2023-03-31 . RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial . Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control. live . https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 . 2023-08-03 . 2023-08-15 . . pt-BR . 2023-04-04.
  5. Web site: Pomalyst Product information . Health Canada . 16 December 2023.
  6. Web site: Imnovid 1 mg hard capsules - Summary of Product Characteristics (SmPC) . (emc) . 16 June 2020 . 21 September 2020 . 26 October 2020 . https://web.archive.org/web/20201026072630/https://www.medicines.org.uk/emc/product/1262/smpc . live .
  7. Web site: Imnovid 1 mg Hard Capsules. Summary of Product Characteristics. 5.2 Pharmacokinetic properties. Celgene Europe Ltd.. 21 August 2016. 22. 27 June 2016. https://web.archive.org/web/20160627190420/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002682/WC500147717.pdf. live.
  8. Web site: Pomalyst- pomalidomide capsule . DailyMed . 7 December 2017 . 21 September 2020 . 20 October 2020 . https://web.archive.org/web/20201020205544/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2b25ef01-5c9e-11e1-b86c-0800200c9a66 . live .
  9. Web site: Drug Approval Package: Pomalyst (pomalidomide) Capsules NDA #204026 . U.S. Food and Drug Administration (FDA) . 8 February 2013 . 21 September 2020 . 29 March 2021 . https://web.archive.org/web/20210329224959/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204026Orig1s000TOC.cfm . live .
  10. Web site: 2020 First Generic Drug Approvals . U.S. Food and Drug Administration . 23 February 2021 . 12 May 2023 . 26 September 2021 . https://web.archive.org/web/20210926025105/https://www.fda.gov/drugs/first-generic-drug-approvals/2020-first-generic-drug-approvals . live .
  11. Web site: Imnovid EPAR . European Medicines Agency (EMA) . 17 September 2018 . 21 September 2020 . 27 October 2020 . https://web.archive.org/web/20201027132039/https://www.ema.europa.eu/en/medicines/human/EPAR/imnovid-previously-pomalidomide-celgene . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  12. Web site: Pomalidomide . National Cancer Institute . 13 February 2013 . 12 May 2023 . 15 January 2023 . https://web.archive.org/web/20230115084913/https://www.cancer.gov/about-cancer/treatment/drugs/pomalidomide . live .
  13. Web site: FDA grants accelerated approval to pomalidomide for Kaposi sarcoma . U.S. Food and Drug Administration . 15 May 2020 . 12 May 2023 . 9 May 2023 . https://web.archive.org/web/20230509061138/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pomalidomide-kaposi-sarcoma . live .
  14. FDA approves pomalidomide for AIDS-related Kaposi sarcoma . National Cancer Institute . 15 May 2020 . 12 May 2023 . 8 May 2023 . https://web.archive.org/web/20230508204356/https://ccr.cancer.gov/news/article/fda-approves-pomalidomide-for-aids-related-kaposi-sarcoma . live .
  15. Web site: Cancer Accelerated Approvals . U.S. Food and Drug Administration . 1 May 2023 . 12 May 2023 . 27 April 2023 . https://web.archive.org/web/20230427230841/https://www.fda.gov/drugs/resources-information-approved-drugs/ongoing-cancer-accelerated-approvals . live .
  16. D'Amato RJ, Loughnan MS, Flynn E, Folkman J . Thalidomide is an inhibitor of angiogenesis . Proceedings of the National Academy of Sciences of the United States of America . 91 . 9 . 4082–5 . April 1994 . 7513432 . 43727 . 10.1073/pnas.91.9.4082 . 1994PNAS...91.4082D . 2364596 . free .
  17. News: Altman D . From Thalidomide to Pomalyst: Better Living Through Chemistry. 2 April 2013. 14 May 2021. 14 May 2021. https://web.archive.org/web/20210514043002/https://damatolab.com/news/thalidomide-pomalyst-better-living-through-chemistry. dead.
  18. D'Amato RJ, Lentzsch S, Anderson KC, Rogers MS . Mechanism of action of thalidomide and 3-aminothalidomide in multiple myeloma . Seminars in Oncology . 28 . 6 . 597–601 . December 2001 . 11740816 . 10.1016/S0093-7754(01)90031-4 .
  19. Lentzsch S, Rogers MS, LeBlanc R, Birsner AE, Shah JH, Treston AM, Anderson KC, D'Amato RJ . S-3-Amino-phthalimido-glutarimide inhibits angiogenesis and growth of B-cell neoplasias in mice . Cancer Research . 62 . 8 . 2300–5 . April 2002 . 11956087 .
  20. Asatsuma-Okumura T, Ito T, Handa H . Molecular mechanisms of cereblon-based drugs . Pharmacology & Therapeutics . 202 . 132–139 . October 2019 . 31202702 . 10.1016/j.pharmthera.2019.06.004 . free .
  21. Streetly MJ, Gyertson K, Daniel Y, Zeldis JB, Kazmi M, Schey SA . Alternate day pomalidomide retains anti-myeloma effect with reduced adverse events and evidence of in vivo immunomodulation . British Journal of Haematology . 141 . 1 . 41–51 . April 2008 . 18324965 . 10.1111/j.1365-2141.2008.07013.x . 37073246 .
  22. Promising Results From 2 Trials Highlighting Pomalidomide Presented At ASH . . 11 December 2008 . 28 October 2012 . 20 September 2018 . https://web.archive.org/web/20180920152609/https://www.medicalnewstoday.com/releases/132590.php . live .
  23. Pomalidomide Therapy in Anemic Patients with Myelofibrosis: Results from a Phase-2 Randomized Multicenter Study . Tefferi A . 8 December 2008 . 50th ASH Annual Meeting and Exposition . San Francisco . 28 October 2012 . 20 September 2018 . https://web.archive.org/web/20180920152602/https://ash.confex.com/ash/2008/webprogram/Paper13194.html . live .
  24. Miguel JS, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M . Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial . The Lancet. Oncology . 14 . 11 . 1055–1066 . September 2013 . 24007748 . 10.1016/s1470-2045(13)70380-2 . 2318/150538 . 4526729 . free . 2 September 2019 . 20 October 2021 . https://web.archive.org/web/20211020032825/https://iris.unito.it/retrieve/handle/2318/150538/60224/1323531.pdf . live .

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