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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.

Medical uses

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

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).

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

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. Because guselkumab is a new medicine, the long-term effects are not fully understood.

Pharmacology

Mechanism of action

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

Pharmacokinetics

• C_max 8.09 μg/mL
• t_max 5.5 days
• volume of distribution 13.5 L
• apparent clearance 0.516 L/day

Commercialization

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

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

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

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

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

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

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

Cost

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

Research and development

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

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). 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.

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.

References

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9. ^ "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.
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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. ^ 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. ^ "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.
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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.
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• Medicine

• Anti-interleukin monoclonal antibodies
• Drugs developed by Johnson & Johnson