Guselkumab
| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Human |
| Target | IL23 |
| Clinical data | |
| Trade names | Tremfya |
| AHFS/Drugs.com | tremfya |
| ATC code | |
| Legal status | |
| Legal status |
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| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
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| UNII | |
| KEGG | |
| Chemical and physical data | |
| Formula | C6402H9864N1676O1994S42 |
| Molar mass | 143561.59 g·mol−1 |
Guselkumab, sold under the trade name Tremfya, is a monoclonal antibody against interleukin-23 used for the treatment of plaque psoriasis.[1][2]
Medical uses
Guselkumab is FDA approved to treat moderate to severe plaque psoriasis in adults.[3] Its use for the treatment of psoriatic arthritis is being explored.[4]
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).[5]
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.[1] For this reason, people with psoriasis being considered for treatment with guselkumab must be screened for tuberculosis infection prior to treatment with guselkumab.[1]
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.[3] As guselkumab is a new medicine, the long term effects are not fully understood.[6]
Pharmacology
Mechanism of action
Guselkumab targets the IL-23 subunit alpha (p19 subunit)[7] preventing it from binding to cell receptors that would otherwise be activated by its presence.[4]
Pharmacokinetics
- Cmax 8.09 µg/mL
- tmax 5.5 days
- volume of distribution 13.5 L
- apparent clearance 0.516 L/day[4]
Commercialization
Guselkumab was developed by Janssen Global Services, LLC.[8] In November 2016, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of guselkumab.[9] In July 2017 Janssen gained US FDA approval to market guselkumab for treatment of plaque psoriasis.[10] Usage for psoriatic arthritis has also been approved in Japan as of April 2018.[11] Guselkumab is manufactured by Janssen Sciences Ireland UC in Cork, Ireland. [12]
Cost
The list price of each 100 mg dose (to be given once every two months) is about $10,000.[13]
Research and development
During development, guselkumab was referred to as CNTO-1959.[4] Guselkumab has undergone phase 3 clinical trials comparing it with adalimumab (Humira) and ustekinumab (Stelara).[8]
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 NCT02207231)[6] 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.[6]
The phase 3 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.[4]
See also
- Ustekinumab, a monoclonal antibody targeting both IL-12 and IL-23 and used to treat plaque psoriasis, launched in the United States under the brand name Stelara
- Tildrakizumab, is a humanized monoclonal IgG1, IL-23-specific antibody approved for the treatment of moderate to severe plaque psoriasis. It is marketed under the brand name Ilumya.
References
- ^ a b c Guselkumab Injection: MedlinePlus Drug Information
- ^ "Guselkumab". 2012. PMID 31643594.
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b Drug Approvals and Databases > Drug Trials Snapshots: TREMFYA
- ^ a b c d e Markham A (Sep 2017). "Guselkumab: First Global Approval". Drugs. 77 (13): 1487–1492. doi:10.1007/s40265-017-0800-7. PMID 28819723.
- ^ JANSSEN ANNOUNCES U.S. FDA APPROVAL OF TREMFYA™ (GUSELKUMAB) FOR THE TREATMENT OF MODERATE TO SEVERE PLAQUE PSORIASIS Johnson & Johnson
- ^ a b c Nakamura M, Lee K, Jeon C, Sekhon S, Afifi L, Yan D, Lee K, Bhutani T (Jun 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, Vega F, Yu N, Wang J, Singh K, Zonin F, Vaisberg E, Churakova T, Liu M, Gorman D, Wagner J, Zurawski S, Liu Y, Abrams JS, Moore KW, Rennick D, de Waal-Malefyt R, Hannum C, Bazan JF, Kastelein RA (Jan 2001). "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.
- ^ a b Janssen Wins FDA Approval for Plaque Psoriasis Treatment Tremfya. 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
- ^ Novel Drug Approvals for 2017
- ^ "MorphoSys' licensee Janssen receives Japanese approval for Tremfya to treat moderate to severe forms of psoriasis & psoriatic arthritis". pharmabiz.com. Retrieved 2018-06-05.
- ^ Guselkumab BLA Approval Letter
- ^ Johnson & Johnson's Tremfya gets its go-ahead to fight Novartis, Lilly in psoriasis. Can it stand out?