Guselkumab

Last updated

Guselkumab
Monoclonal antibody
Type Whole antibody
Source Human
Target IL23
Clinical data
Trade names Tremfya
AHFS/Drugs.com Monograph
MedlinePlus a617036
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
Formula C6402H9864N1676O1994S42
Molar mass 143561.59 g·mol−1

Guselkumab, sold under the brand name Tremfya, is a monoclonal antibody against interleukin-23 used for the treatment of plaque psoriasis, psoriatic arthritis, and ulcerative colitis. [7] [8] [9]

Contents

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). [10]

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, [11] joint pain, diarrhea, gastroenteritis, fungal skin infections and herpes simplex infections. [12] Because guselkumab is a new medicine, the long-term effects are not fully understood. [13]

Pharmacology

Mechanism of action

Guselkumab targets the IL-23 subunit alpha (p19 subunit) [14] preventing it from binding to cell receptors that would otherwise be activated by its presence. [15]

Pharmacokinetics

Commercialization

Guselkumab was developed by Janssen Pharmaceuticals. [16] In November 2016, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of guselkumab. [17]

In July 2017, Janssen gained US FDA approval to market guselkumab for treatment of plaque psoriasis. [18]

In November 2017 Health Canada approved guselkumab to be marketed for the treatment of plaque psoriasis in Canada. [19] In September 2020 approval was expanded to include the treatment of adults with psoriatic arthritis. [20]

In April 2018, guselkumab was approved in Japan for the treatment psoriatic arthritis. [21]

In July 2020, the FDA approved guselkumab as the first IL-23 inhibitor to treat active psoriatic arthritis (PsA) in the USA. [22] [23]

Guselkumab is manufactured by Janssen Sciences Ireland UC in Cork, Ireland. [24]

In September 2024, Janssen received FDA approval to market guselkumab for the treatment of moderately to severely active ulcerative colitis in adults. [9]

Cost

The list price of each 100 mg dose (to be given once every two months) is about $10,000. [25]

Research and development

During development, guselkumab was referred to as CNTO-1959. [15] Guselkumab has undergone phase 3 clinical trials comparing it with adalimumab (Humira) and ustekinumab (Stelara). [16]

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). [13] 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. [13]

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. [15]

Related Research Articles

<span class="mw-page-title-main">Psoriasis</span> Non-contagious skin disease

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by patches of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.

<span class="mw-page-title-main">Infliximab</span> Biopharmaceutical drug for autoimmune disorders

Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, and Behçet's disease. It is given by slow injection into a vein, typically at six- to eight-week intervals.

<span class="mw-page-title-main">Psoriatic arthritis</span> Long-term inflammatory arthritis

Psoriatic arthritis (PsA) is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. This often happens in association with changes to the nails such as small depressions in the nail (pitting), thickening of the nails, and detachment of the nail from the nailbed. Skin changes consistent with psoriasis frequently occur before the onset of psoriatic arthritis but psoriatic arthritis can precede the rash in 15% of affected individuals. It is classified as a type of seronegative spondyloarthropathy.

Etanercept, sold under the brand name Enbrel among others, is a biologic medical product that is used to treat autoimmune diseases by interfering with tumor necrosis factor (TNF), a soluble inflammatory cytokine, by acting as a TNF inhibitor. It has US Food and Drug Administration (FDA) approval to treat rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. Tumor necrosis factor alpha (TNFα) is the "master regulator" of the inflammatory (immune) response in many organ systems. Autoimmune diseases are caused by an overactive immune response. Etanercept has the potential to treat these diseases by inhibiting TNF-alpha.

Adalimumab, sold under the brand name Humira and others, is a disease-modifying antirheumatic drug and monoclonal antibody used to treat rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, and uveitis. It is administered by subcutaneous injection. It works by inactivating tumor necrosis factor-alpha (TNFα).

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections, congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

<span class="mw-page-title-main">Biological therapy for inflammatory bowel disease</span>

Biological therapy, the use of medications called biopharmaceuticals or biologics that are tailored to specifically target an immune or genetic mediator of disease, plays a major role in the treatment of inflammatory bowel disease. Even for diseases of unknown cause, molecules that are involved in the disease process have been identified, and can be targeted for biological therapy. Many of these molecules, which are mainly cytokines, are directly involved in the immune system. Biological therapy has found a niche in the management of cancer, autoimmune diseases, and diseases of unknown cause that result in symptoms due to immune related mechanisms.

Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous or exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.

Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23.

<span class="mw-page-title-main">Golimumab</span> Pharmaceutical drug

Golimumab, sold under the brand name Simponi, is a human monoclonal antibody which is used as an immunosuppressive medication. Golimumab targets tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory molecule and hence is a TNF inhibitor. Profound reduction in C-reactive protein (CRP) levels, interleukin (IL)-6, intercellaular adhesion molecules (ICAM)-1, matrix metalloproteinase (MMP)-3, and vascular endothelial growth factor (VEGF) demonstrates golimumab as an effective modulator of inflammatory markers and bone metabolism. Golimumab is given via subcutaneous injection.

MorphoSys AG is a German biopharmaceutical company founded in 1992. The company is headquartered near Munich, Germany, and has a wholly owned subsidiary, MorphoSys US Inc., in Boston, Massachusetts, in the US. The company has various antibody, protein and peptide technologies that it uses to discover and develop both proprietary and partnered drug candidates. The company has more than 100 drugs in its wider pipeline that are being investigated for a variety of diseases. While many of these are being developed in partnership with pharma and biotech companies, MorphoSys also has a proprietary pipeline with a focus on cancer and autoimmune diseases.

Briakinumab (ABT-874) is a human monoclonal antibody being developed by Abbott Laboratories for the treatment of rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. As of 2011 drug development for psoriasis has been discontinued in the U.S. and Europe.

<span class="mw-page-title-main">Tofacitinib</span> Medication

Tofacitinib, sold under the brand Xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, polyarticular course juvenile idiopathic arthritis, and ulcerative colitis. It is a janus kinase (JAK) inhibitor, discovered and developed by the National Institutes of Health and Pfizer.

Ixekizumab, sold under the brand name Taltz, is an injectable medication for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody. The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.

<span class="mw-page-title-main">Secukinumab</span> Monoclonal antibody against IL-17

Secukinumab, sold under the brand name Cosentyx among others, is a human IgG1κ monoclonal antibody used for the treatment of psoriasis, ankylosing spondylitis, and psoriatic arthritis. It binds to the protein interleukin (IL)-17A and is marketed by Novartis.

Sarilumab, sold under the brand name Kevzara, is a human monoclonal antibody medication against the interleukin-6 receptor. Regeneron Pharmaceuticals and Sanofi developed the drug for the treatment of rheumatoid arthritis (RA), for which it received US FDA approval on 22 May 2017 and European Medicines Agency approval on 23 June 2017.

Tildrakizumab, sold under the brand name Ilumya among others, is a monoclonal antibody designed for the treatment of immunologically mediated inflammatory disorders. It is approved for the treatment of adults with moderate-to-severe plaque psoriasis in the United States and in the European Union.

Risankizumab, sold under the brand name Skyrizi, is a humanized monoclonal antibody used for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. It is designed to target interleukin 23A (IL-23A). It is given by subcutaneous injection.

<span class="mw-page-title-main">Upadacitinib</span> Biopharmaceutical drug

Upadacitinib, sold under the brand name Rinvoq, is a medication used for the treatment of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and axial spondyloarthritis. Upadacitinib is a Janus kinase (JAK) inhibitor that works by blocking the action of enzymes called Janus kinases. These enzymes are involved in setting up processes that lead to inflammation, and blocking their effect brings inflammation in the joints under control.

Bimekizumab, sold under the brand name Bimzelx, is a humanized anti-IL17A, anti-IL-17F, and anti-IL17AF monoclonal antibody that is used to treat plaque psoriasis, psoriatic arthritis, axial spondyloarthritis, and ankylosing spondylitis.

References

  1. ↑ "Tremfya (Guselkumab) Australian Product Information". Department of Health, Therapeutic Goods Administration. The Australian Government.
  2. ↑ "Product information". health-products.canada.ca. 27 November 2017. Retrieved 18 March 2024.
  3. ↑ "Skin health". Health Canada . 9 May 2018. Retrieved 13 April 2024.
  4. ↑ "Tremfya 100 mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC)". (emc). 1 November 2020. Retrieved 12 June 2021.
  5. 1 2 "Tremfya- guselkumab injection". DailyMed. Retrieved 22 January 2021.
  6. ↑ "European Medicines Agency". European Medicines Agency {EMA). 17 September 2018. Retrieved 12 June 2021.
  7. 1 2 3 "Guselkumab Injection". MedlinePlus Drug Information.
  8. ↑ "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.
  9. 1 2 "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.
  10. ↑ "Janssen Announces U.S. FDA Approval of Tremfya (Guselkumab) for the Treatment of Moderate to Severe Plaque Psoriasis". Johnson & Johnson. 13 July 2017.
  11. ↑ 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.
  12. ↑ "TREMFYA". Drug Approvals and Databases > Drug Trials Snapshots. U.S. Food and Drug Administration. 3 August 2017.
  13. 1 2 3 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.
  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. 1 2 3 4 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. 1 2 "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.
  20. ↑ "Regulatory Decision Summary for Tremfya". Drug and Health Products Portal. 4 September 2020. Retrieved 18 March 2024.
  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.
  25. ↑ 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.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.