Guselkumab

Pregnancy
categoryRoutes of
administrationSubcutaneousATC codeLegal statusLegal status IdentifiersCAS NumberDrugBankChemSpiderUNIIKEGGChemical and physical dataFormulaC₆₄₀₂H₉₈₆₄N₁₆₇₆O₁₉₉₄S₄₂Molar 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.^[6][7]

Medical uses

Guselkumab is indicated to treat moderate to severe plaque psoriasis, and psoriatic arthritis in adults.^[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).^[8]

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.^[6] For this reason, people with psoriasis being considered for treatment with guselkumab must be screened for tuberculosis infection prior to treatment with guselkumab.^[6]

The most common side effects for guselkumab are upper respiratory tract infections, headache, injection site reactions,^[9] joint pain, diarrhea, gastroenteritis, fungal skin infections and herpes simplex infections.^[10] Because guselkumab is a new medicine, the long-term effects are not fully understood.^[11]

Pharmacology

Mechanism of action

Guselkumab targets the IL-23 subunit alpha (p19 subunit)^[12] preventing it from binding to cell receptors that would otherwise be activated by its presence.^[13]

Pharmacokinetics

• C_max 8.09 µg/mL
• t_max 5.5 days
• volume of distribution 13.5 L
• apparent clearance 0.516 L/day^[13]

Commercialization

Guselkumab was developed by Janssen Global Services, LLC.^[14] In November 2016, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of guselkumab.^[15]

In July 2017, Janssen gained US FDA approval to market guselkumab for treatment of plaque psoriasis.^[16]

In November 2017 Health Canada approved guselkumab to be marketed for the treatment of plaque psoriasis in Canada. ^[17] In September 2020 approval was expanded to include the treatment of adults with psoriatic arthritis. ^[18]

In April 2018, guselkumab was approved in Japan for the treatment psoriatic arthritis.^[19]

In July 2020, the FDA approved as the first IL-23 inhibitor to treat active psoriatic arthritis (PsA) in the USA. ^[20][21]

Guselkumab is manufactured by Janssen Sciences Ireland UC in Cork, Ireland.^[22]

Cost

The list price of each 100 mg dose (to be given once every two months) is about $10,000.^[23]

Research and development

During development, guselkumab was referred to as CNTO-1959.^[13] Guselkumab has undergone phase 3 clinical trials comparing it with adalimumab (Humira) and ustekinumab (Stelara).^[14]

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).^[11] 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.^[11]

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.^[13]

References

External links

• "Guselkumab". Drug Information Portal. U.S. National Library of Medicine.