Guselkumab

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

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

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]

In October 2022, J&J announced the results of a 38-week Phase IIa clinical trial ("VEGA") for adults with moderate to severe ulcerative colitis who received a 12-week therapy of Tremfya and golimumab followed by a transition only to Tremfya. The results of the combined therapy showed a achieved a remission rate of 47.9%, a higher rate than when Tremfya was used alone (31%).[20][21]

References
  1. "Tremfya (Guselkumab) Australian Product Information". Department of Health, Therapeutic Goods Administration. The Australian Government.
  2. "Tremfya 100 mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC)". (emc). 1 November 2020. Retrieved 12 June 2021.
  3. "Tremfya- guselkumab injection". DailyMed. Retrieved 22 January 2021.
  4. "European Medicines Agency". European Medicines Agency {EMA). Retrieved 12 June 2021.
  5. "Guselkumab Injection". MedlinePlus Drug Information.
  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.
  8. "TREMFYA". Drug Approvals and Databases > Drug Trials Snapshots. U.S. Food and Drug Administration. 3 August 2017.
  9. 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.
  10. 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): 715–25. doi:10.1016/S1074-7613(00)00070-4. PMID 11114383.
  11. Markham A (September 2017). "Guselkumab: First Global Approval". Drugs. 77 (13): 1487–1492. doi:10.1007/s40265-017-0800-7. PMID 28819723. S2CID 35810454.
  12. "Janssen Wins FDA Approval for Plaque Psoriasis Treatment Tremfya". Genetic Engineering & Biotechnology News. 14 July 2017.
  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.
  14. "Novel Drug Approvals for 2017". U.S. Food and Drug Administration. 25 January 2021.
  15. "MorphoSys' licensee Janssen receives Japanese approval for Tremfya to treat moderate to severe forms of psoriasis & psoriatic arthritis". pharmabiz.com. Retrieved 2018-06-05.
  16. "FDA approves Tremfya (guselkumab) for psoriatic arthritis". www.mdedge.com. Retrieved 2020-07-15.
  17. "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. 2020-07-14. Retrieved 2020-09-06.
  18. "Guselkumab BLA Approval Letter" (PDF). U.S. Food and Drug Administration.
  19. 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.
  20. Johnson, Janssen Pharmaceutical Companies of Johnson &. "Results of Novel Clinical Study of Guselkumab and Golimumab Combination Therapy Show Adults with Moderately to Severely Active Ulcerative Colitis Maintained Higher Rates of Clinical, Histologic, and Endoscopic Remission at Week 38". www.prnewswire.com. Retrieved 2022-10-11.
  21. Janssen Research & Development, LLC (2021-12-30). "A Phase 2a Randomized, Double-blind, Active-controlled, Parallel-group, Multicenter, Proof-of-concept Clinical Study to Evaluate the Efficacy and Safety of Combination Therapy With Guselkumab and Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis". {{cite journal}}: Cite journal requires |journal= (help)
  • "Guselkumab". Drug Information Portal. U.S. National Library of Medicine.
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