Chemistry:Guselkumab

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Short description: Monoclonal antibody
Guselkumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL23
Clinical data
Trade namesTremfya
AHFS/Drugs.comMonograph
MedlinePlusa617036
License data
Pregnancy
category
  • AU: B1
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6402H9864N1676O1994S42
Molar mass143561.59 g·mol−1

Guselkumab, sold under the brand name Tremfya, is a monoclonal antibody against interleukin-23 used for the treatment of plaque psoriasis.[5][6]

Medical uses

Guselkumab is indicated to treat moderate to severe plaque psoriasis, and psoriatic arthritis in adults.[3]

Guselkumab is provided as a subcutaneous injection of 100 mg given every eight weeks (except for the second dose, which is given four weeks after the first dose).[7]

Adverse effects

Because guselkumab lowers the release of immune system signalling molecules, patients may have a higher risk of getting infections from bacteria, viruses, and fungi.[5] For this reason, people with psoriasis being considered for treatment with guselkumab must be screened for tuberculosis infection prior to treatment with guselkumab.[5]

The most common side effects for guselkumab are upper respiratory tract infections, headache, injection site reactions, joint pain, diarrhea, gastroenteritis, fungal skin infections and herpes simplex infections.[8] Because guselkumab is a new medicine, the long-term effects are not fully understood.[9]

Pharmacology

Mechanism of action

Guselkumab targets the IL-23 subunit alpha (p19 subunit)[10] preventing it from binding to cell receptors that would otherwise be activated by its presence.[11]

Pharmacokinetics

  • Cmax 8.09 µg/mL
  • tmax 5.5 days
  • volume of distribution 13.5 L
  • apparent clearance 0.516 L/day[11]

Commercialization

Guselkumab was developed by Janssen Global Services, LLC.[12] In November 2016, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of guselkumab.[13]

In July 2017, Janssen gained US FDA approval to market guselkumab for treatment of plaque psoriasis.[14]

In April 2018, Guselkumab was approved in Japan for the treatment psoriatic arthritis.[15]

In July 2020, the FDA approved as the first IL-23 inhibitor to treat active psoriatic arthritis (PsA) in the USA. [16][17]

Guselkumab is manufactured by Janssen Sciences Ireland UC in Cork, Ireland.[18]

Cost

The list price of each 100 mg dose (to be given once every two months) is about $10,000.[19]

Research and development

During development, guselkumab was referred to as CNTO-1959.[11] Guselkumab has undergone phase 3 clinical trials comparing it with adalimumab (Humira) and ustekinumab (Stelara).[12]

The safety and efficacy of guselkumab was compared to a placebo and to adalimumab in the "VOYAGE 1" and "VOYAGE 2" phase 3 clinical trials (ClinicalTrials.gov IDs: NCT02207231 and NCT02207244).[9] Preliminary results indicated that a significantly higher proportion of patients taking guselkumab had better skin clearance compared to those taking the other treatments. At week 16, 73.3% of patients taking guselkumab achieved a PASI 90 (90% reduction in PASI score from baseline), vs 49.7% of those taking adalimumab; additionally, 91.2% of patients taking guselkumab achieved a PASI 75 (75% reduction in PASI score from baseline), vs 73.1% of those taking adalimumab.[9]

The phase III clinical trial "NAVIGATE" (ClinicalTrials.gov ID: NCT02203032) included only patients who had poor responses to treatment with ustekinumab. It showed that patients who switched to guselkumab from ustekinumab did better than those who remained on ustekinumab.[11]

References

  1. ↑ "Tremfya (Guselkumab) Australian Product Information". Department of Health, Therapeutic Goods Administration. The Australian Government. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2018-PI-01506-1. 
  2. ↑ "Tremfya 100 mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC)". 1 November 2020. https://www.medicines.org.uk/emc/product/9587/smpc. 
  3. ↑ 3.0 3.1 "Tremfya- guselkumab injection". https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e6dc9ae-1c4c-42d9-87aa-c315ecc51b56. 
  4. ↑ "European Medicines Agency". https://www.ema.europa.eu/en/medicines/human/EPAR/tremfya. 
  5. ↑ 5.0 5.1 5.2 "Guselkumab Injection". MedlinePlus Drug Information. https://medlineplus.gov/druginfo/meds/a617036.html. 
  6. ↑ "Guselkumab". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. (National Institute of Diabetes and Digestive and Kidney Diseases). June 2018. PMID 31643594. 
  7. ↑ "Janssen Announces U.S. FDA Approval of Tremfya (Guselkumab) for the Treatment of Moderate to Severe Plaque Psoriasis". Johnson & Johnson. 13 July 2017. https://www.jnj.com/media-center/press-releases/janssen-announces-us-fda-approval-of-tremfya-guselkumab-for-the-treatment-of-moderate-to-severe-plaque-psoriasis. 
  8. ↑ "TREMFYA". Drug Approvals and Databases > Drug Trials Snapshots. U.S. Food and Drug Administration. 3 August 2017. https://www.fda.gov/Drugs/InformationOnDrugs/ucm568274.htm. 
  9. ↑ 9.0 9.1 9.2 "Guselkumab for the Treatment of Psoriasis: A Review of Phase III Trials". Dermatology and Therapy 7 (3): 281–292. September 2017. doi:10.1007/s13555-017-0187-0. PMID 28639011. 
  10. ↑ "Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12". Immunity 13 (5): 715–25. November 2000. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383. 
  11. ↑ 11.0 11.1 11.2 11.3 "Guselkumab: First Global Approval". Drugs 77 (13): 1487–1492. September 2017. doi:10.1007/s40265-017-0800-7. PMID 28819723. 
  12. ↑ 12.0 12.1 "Janssen Wins FDA Approval for Plaque Psoriasis Treatment Tremfya". Genetic Engineering & Biotechnology News. 14 July 2017. http://www.genengnews.com/gen-news-highlights/janssen-wins-fda-approval-for-plaque-psoriasis-treatment-tremfya/81254657. 
  13. ↑ "Janssen Submits Application to EMA Seeking Approval of Anti-Interleukin-23 Monoclonal Antibody Guselkumab for the Treament of Moderate-to-Severe Plaque Psoriasis". Janssen. http://www.janssen.com/janssen-submits-application-ema-seeking-approval-anti-interleukin-23-monoclonal-antibody-guselkumab. 
  14. ↑ "Novel Drug Approvals for 2017". U.S. Food and Drug Administration. 25 January 2021. https://www.fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm537040.htm. 
  15. ↑ "MorphoSys' licensee Janssen receives Japanese approval for Tremfya to treat moderate to severe forms of psoriasis & psoriatic arthritis". http://pharmabiz.com/NewsDetails.aspx?aid=108225&sid=2. 
  16. ↑ "FDA approves Tremfya (guselkumab) for psoriatic arthritis" (in en). https://www.mdedge.com/rheumatology/article/225460/psoriatic-arthritis/fda-approves-tremfya-guselkumab-psoriatic-arthritis. 
  17. ↑ "DGAP-News: MororphoSys's Licensee Janssen Announces Approval of Tremfya (Guselkumab) by U.S. FDA for Treatment of Adults with Active Psoriatic Arthritis" (in en). Bloomberg.com. 14 July 2020. https://www.bloomberg.com/press-releases/2020-07-14/dgap-news-mororphosys-s-licensee-janssen-announces-approval-of-tremfya-guselkumab-by-u-s-fda-for-treatment-of-adults-with. 
  18. ↑ "Guselkumab BLA Approval Letter". U.S. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/761061Orig1s000ltr.pdf. 
  19. ↑ "Johnson & Johnson's Tremfya gets its go-ahead to fight Novartis, Lilly in psoriasis. Can it stand out?". Fierce Pharma. 13 July 2017. http://www.fiercepharma.com/pharma/johnson-johnson-s-tremfya-gets-its-green-light-to-challenge-novartis-lilly-and-more-ultra. 

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