Guselkumab
- US DailyMed: Guselkumab
category
- AU: B1
administration
- L04AC16 (WHO)
- AU: S4 (Prescription only)[1]
- CA: Rx-only, Schedule D[2][3]
- UK: POM (Prescription only)[4]
- US: ℞-only[5]
- EU: Rx-only[6]
- 1350289-85-8
- DB11834
- none
- 089658A12D
- D10438
Guselkumab, sold under the brand name Tremfya, is a monoclonal antibody against interleukin-23 used for the treatment of plaque psoriasis.[7][8]
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).[9]
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,[10] joint pain, diarrhea, gastroenteritis, fungal skin infections and herpes simplex infections.[11] Because guselkumab is a new medicine, the long-term effects are not fully understood.[12]
Pharmacology
Mechanism of action
Guselkumab targets the IL-23 subunit alpha (p19 subunit)[13] preventing it from binding to cell receptors that would otherwise be activated by its presence.[14]
Pharmacokinetics
- Cmax 8.09 μg/mL
- tmax 5.5 days
- volume of distribution 13.5 L
- apparent clearance 0.516 L/day[14]
Commercialization
Guselkumab was developed by Janssen Global Services, LLC.[15] In November 2016, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of guselkumab.[16]
In July 2017, Janssen gained US FDA approval to market guselkumab for treatment of plaque psoriasis.[17]
In November 2017 Health Canada approved guselkumab to be marketed for the treatment of plaque psoriasis in Canada. [18] In September 2020 approval was expanded to include the treatment of adults with psoriatic arthritis. [19]
In April 2018, guselkumab was approved in Japan for the treatment psoriatic arthritis.[20]
In July 2020, the FDA approved as the first IL-23 inhibitor to treat active psoriatic arthritis (PsA) in the USA. [21][22]
Guselkumab is manufactured by Janssen Sciences Ireland UC in Cork, Ireland.[23]
Cost
The list price of each 100 mg dose (to be given once every two months) is about $10,000.[24]
Research and development
During development, guselkumab was referred to as CNTO-1959.[14] Guselkumab has undergone phase 3 clinical trials comparing it with adalimumab (Humira) and ustekinumab (Stelara).[15]
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).[12] 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.[12]
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.[14]
References
- ^ "Tremfya (Guselkumab) Australian Product Information". Department of Health, Therapeutic Goods Administration. The Australian Government.
- ^ "Product information". health-products.canada.ca. 27 November 2017. Retrieved 18 March 2024.
- ^ "Skin health". Health Canada. 9 May 2018. Retrieved 13 April 2024.
- ^ "Tremfya 100 mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC)". (emc). 1 November 2020. Retrieved 12 June 2021.
- ^ a b "Tremfya- guselkumab injection". DailyMed. Retrieved 22 January 2021.
- ^ "European Medicines Agency". European Medicines Agency {EMA). 17 September 2018. Retrieved 12 June 2021.
- ^ a b c "Guselkumab Injection". MedlinePlus Drug Information.
- ^ "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.
- ^ "Janssen Announces U.S. FDA Approval of Tremfya (Guselkumab) for the Treatment of Moderate to Severe Plaque Psoriasis". Johnson & Johnson. 13 July 2017.
- ^ 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.
- ^ "TREMFYA". Drug Approvals and Databases > Drug Trials Snapshots. U.S. Food and Drug Administration. 3 August 2017.
- ^ 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.
- ^ 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.
- ^ 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.
- ^ a b "Janssen Wins FDA Approval for Plaque Psoriasis Treatment Tremfya". Genetic Engineering & Biotechnology News. 14 July 2017.
- ^ "Janssen Submits Application to EMA Seeking Approval of Anti-Interleukin-23 Monoclonal Antibody Guselkumab for the Treament of Moderate-to-Severe Plaque Psoriasis". Janssen. Archived from the original on 7 November 2017. Retrieved 1 November 2017.
- ^ "Novel Drug Approvals for 2017". U.S. Food and Drug Administration. 25 January 2021.
- ^ "Regulatory Decision Summary for Tremfya". Drug and Health Products Portal. 10 November 2017. Retrieved 18 March 2024.
- ^ "Regulatory Decision Summary for Tremfya". Drug and Health Products Portal. 4 September 2020. Retrieved 18 March 2024.
- ^ "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.
- ^ "FDA approves Tremfya (guselkumab) for psoriatic arthritis". www.mdedge.com. Retrieved 15 July 2020.
- ^ "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.
- ^ "Guselkumab BLA Approval Letter" (PDF). U.S. Food and Drug Administration.
- ^ 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.
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