Langbahn Team – Weltmeisterschaft

Guselkumab

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, psoriatic arthritis, and ulcerative colitis.[7][8][9]

Medical uses

Guselkumab is indicated to treat moderate to severe plaque psoriasis, and psoriatic arthritis in adults.[5]

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).[10]

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.[7] For this reason, people with psoriasis being considered for treatment with guselkumab must be screened for tuberculosis infection prior to treatment with guselkumab.[7]

The most common side effects for guselkumab are upper respiratory tract infections, headache, injection site reactions,[11] joint pain, diarrhea, gastroenteritis, fungal skin infections and herpes simplex infections.[12] Because guselkumab is a new medicine, the long-term effects are not fully understood.[13]

Pharmacology

Mechanism of action

Guselkumab targets the IL-23 subunit alpha (p19 subunit)[14] preventing it from binding to cell receptors that would otherwise be activated by its presence.[15]

Pharmacokinetics

  • Cmax 8.09 μg/mL
  • tmax 5.5 days
  • volume of distribution 13.5 L
  • apparent clearance 0.516 L/day[15]

Commercialization

Guselkumab was developed by Janssen Pharmaceuticals.[16] In November 2016, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of guselkumab.[17]

In July 2017, Janssen gained US FDA approval to market guselkumab for treatment of plaque psoriasis.[18]

In November 2017 Health Canada approved guselkumab to be marketed for the treatment of plaque psoriasis in Canada.[19] In September 2020 approval was expanded to include the treatment of adults with psoriatic arthritis.[20]

In April 2018, guselkumab was approved in Japan for the treatment psoriatic arthritis.[21]

In July 2020, the FDA approved guselkumab as the first IL-23 inhibitor to treat active psoriatic arthritis (PsA) in the USA.[22][23]

Guselkumab is manufactured by Janssen Sciences Ireland UC in Cork, Ireland.[24]

In September 2024, Janssen received FDA approval to market guselkumab for the treatment of moderately to severely active ulcerative colitis in adults.[9]

Cost

The list price of each 100 mg dose (to be given once every two months) is about $10,000.[25]

Research and development

During development, guselkumab was referred to as CNTO-1959.[15] Guselkumab has undergone phase 3 clinical trials comparing it with adalimumab (Humira) and ustekinumab (Stelara).[16]

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).[13] 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.[13]

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.[15]

References

  1. ^ "Tremfya (Guselkumab) Australian Product Information". Department of Health, Therapeutic Goods Administration. The Australian Government.
  2. ^ "Product information". health-products.canada.ca. 27 November 2017. Retrieved 18 March 2024.
  3. ^ "Skin health". Health Canada. 9 May 2018. Retrieved 13 April 2024.
  4. ^ "Tremfya 100 mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC)". (emc). 1 November 2020. Retrieved 12 June 2021.
  5. ^ a b "Tremfya- guselkumab injection". DailyMed. Retrieved 22 January 2021.
  6. ^ "European Medicines Agency". European Medicines Agency {EMA). 17 September 2018. Retrieved 12 June 2021.
  7. ^ a b c "Guselkumab Injection". MedlinePlus Drug Information.
  8. ^ "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.
  9. ^ a b "TREMFYA® (guselkumab) receives U.S. FDA approval for adults with moderately to severely active ulcerative colitis, strengthening Johnson & Johnson's leadership in inflammatory bowel disease". Johnson & Johnson.
  10. ^ "Janssen Announces U.S. FDA Approval of Tremfya (Guselkumab) for the Treatment of Moderate to Severe Plaque Psoriasis". Johnson & Johnson. 13 July 2017.
  11. ^ Kim PJ, Lansang RP, Vender R (July 2023). "A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections". Journal of Cutaneous Medicine and Surgery. 27 (4): 358–367. doi:10.1177/12034754231188444. PMC 10486173. PMID 37533141.
  12. ^ "TREMFYA". Drug Approvals and Databases > Drug Trials Snapshots. U.S. Food and Drug Administration. 3 August 2017.
  13. ^ a b c Nakamura M, Lee K, Jeon C, Sekhon S, Afifi L, Yan D, et al. (September 2017). "Guselkumab for the Treatment of Psoriasis: A Review of Phase III Trials". Dermatology and Therapy. 7 (3): 281–292. doi:10.1007/s13555-017-0187-0. PMC 5574739. PMID 28639011.
  14. ^ Oppmann B, Lesley R, Blom B, Timans JC, Xu Y, Hunte B, et al. (November 2000). "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): 715–725. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383.
  15. ^ a b c d Markham A (September 2017). "Guselkumab: First Global Approval". Drugs. 77 (13): 1487–1492. doi:10.1007/s40265-017-0800-7. PMID 28819723. S2CID 35810454.
  16. ^ a b "Janssen Wins FDA Approval for Plaque Psoriasis Treatment Tremfya". Genetic Engineering & Biotechnology News. 14 July 2017.
  17. ^ "Janssen Submits Application to EMA Seeking Approval of Anti-Interleukin-23 Monoclonal Antibody Guselkumab for the Treatment of Moderate-to-Severe Plaque Psoriasis". Janssen. Archived from the original on 7 November 2017. Retrieved 1 November 2017.
  18. ^ "Novel Drug Approvals for 2017". U.S. Food and Drug Administration. 25 January 2021.
  19. ^ "Regulatory Decision Summary for Tremfya". Drug and Health Products Portal. 10 November 2017. Retrieved 18 March 2024.
  20. ^ "Regulatory Decision Summary for Tremfya". Drug and Health Products Portal. 4 September 2020. Retrieved 18 March 2024.
  21. ^ "MorphoSys' licensee Janssen receives Japanese approval for Tremfya to treat moderate to severe forms of psoriasis & psoriatic arthritis". pharmabiz.com. Archived from the original on 29 April 2021. Retrieved 5 June 2018.
  22. ^ "FDA approves Tremfya (guselkumab) for psoriatic arthritis". www.mdedge.com. Retrieved 15 July 2020.
  23. ^ "DGAP-News: MororphoSys's Licensee Janssen Announces Approval of Tremfya (Guselkumab) by U.S. FDA for Treatment of Adults with Active Psoriatic Arthritis". Bloomberg.com. 14 July 2020. Retrieved 6 September 2020.
  24. ^ "Guselkumab BLA Approval Letter" (PDF). U.S. Food and Drug Administration.
  25. ^ Helfand C (13 July 2017). "Johnson & Johnson's Tremfya gets its go-ahead to fight Novartis, Lilly in psoriasis. Can it stand out?". Fierce Pharma.
Quelle: https://en.wikipedia.org/wiki/Tremfya