Tralokinumab

Tralokinumab
Tralokinumab Fab fragment bound to IL-13. From PDB 5L6Y​.
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL-13
Clinical data
Pronunciation/ˌtreɪləˈkɪnjʊmæb/
TRAY-lə-KIN-yuu-mab
Trade namesAdtralza, Adbry
Other namesCAT-354, tralokinumab-ldrm
License data
Routes of
administration		Subcutaneous
ATC code
Legal status
Legal status
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6374H9822N1698O2014S44
Molar mass143875.20 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Tralokinumab sold under the brand names Adtralza (EU/UK) and Adbry (US) among others, is a human monoclonal antibody used for the treatment of atopic dermatitis.[3][5] Tralokinumab targets the cytokine interleukin 13.[8]

The most common side effects include upper respiratory tract infections (colds and other infections of the nose and throat), reactions at the injection site, and redness and discomfort in the eye.[5]

Tralokinumab was approved for medical use in the European Union and in the United Kingdom in June 2021.[3][5][9] It was approved for medical use in the United States in December 2021.[7][10][4] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[11]

Medical uses

Tralokinumab is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.[5][3]

In the United States, tralokinumab is indicated for the treatment of moderate-to-severe atopic dermatitis in adults whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.[4][7]

Discovery and development

Tralokinumab was discovered by Cambridge Antibody Technology scientists[12][13][14] using protein optimization based on Ribosome Display.[15] They used the extensive data sets from ribosome display to patent protect CAT-354 in a world-first of sequence-activity-relationship claims.[14] In 2004, clinical development of CAT-354 was initiated with this first study completing in 2005.[16] On 21 July 2011, MedImmune LLC initiated a Phase IIb, randomized, double-blind study to evaluate the efficacy of tralokinumab in adults with asthma.[17][18][19]

In 2016, MedImmune and AstraZeneca started developing tralokinumab for asthma (Phase III) and atopic dermatitis (Phase IIb) while clinical development for moderate-to-severe ulcerative colitis and idiopathic pulmonary fibrosis (IPF) have been discontinued.[16] In July of that year AstraZeneca licensed tralokinumab to Leo Pharma for skin diseases.[20]

A phase IIb study of tralokinumab found that treatment was associated with early and sustained improvements in atopic dermatitis symptoms and tralokinumab had an acceptable safety and tolerability profile, thereby providing evidence for targeting IL-13 in patients with atopic dermatitis.[21]

In June 2017, Leo Pharma started phase III clinical trials with tralokinumab in atopic dermatitis.[22]

Society and culture

In April 2021, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Adtralza, intended for the treatment of moderate‑to‑severe atopic dermatitis.[23] The applicant for this medicinal product is LEO Pharma A/S.[23] Tralokinumab was approved for medical use in the European Union in June 2021.[5]

Names

Tralokinumab is the international nonproprietary name (INN)[24] and the United States Adopted Name (USAN).[25]

References

  1. ^ "Summary Basis of Decision (SBD) for Adtralza". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
  2. ^ "Health product highlights 2021: Annexes of products approved in 2021". Health Canada. 3 August 2022. Retrieved 25 March 2024.
  3. ^ a b c d "Adtralza 150 mg solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC)". (emc). 5 July 2021. Archived from the original on 9 July 2021. Retrieved 9 July 2021.
  4. ^ a b c "Adbry- tralokinumab-ldrm injection, solution". DailyMed. Archived from the original on 13 January 2022. Retrieved 13 January 2022.
  5. ^ a b c d e f "Adtralza EPAR". European Medicines Agency (EMA). 20 April 2021. Archived from the original on 29 June 2021. Retrieved 9 July 2021. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  6. ^ "Adtralza Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  7. ^ a b c "LEO Pharma announces FDA approval of Adbry (tralokinumab-ldrm) as the first and only treatment specifically targeting IL-13 for adults with moderate-to-severe atopic dermatitis" (Press release). LEO Pharma. 28 December 2021. Archived from the original on 5 October 2022. Retrieved 22 January 2023 – via Business Wire.
  8. ^ Kopf M, Bachmann MF, Marsland BJ (September 2010). "Averting inflammation by targeting the cytokine environment". Nature Reviews. Drug Discovery. 9 (9): 703–18. doi:10.1038/nrd2805. PMID 20811382. S2CID 23769909.
  9. ^ "LEO Pharma announces European Commission approval of Adtralza (tralokinumab) as the first and only treatment specifically targeting IL-13 for adults with moderate-to-severe atopic dermatitis" (Press release). LEO Pharma. 22 June 2021. Archived from the original on 26 October 2021. Retrieved 22 January 2023 – via Business Wire.
  10. ^ "Drug Approval Package: Adbry". U.S. Food and Drug Administration (FDA). 25 January 2022. Archived from the original on 11 October 2022. Retrieved 22 January 2023.
  11. ^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  12. ^ Thom G, Cockroft AC, Buchanan AG, Candotti CJ, Cohen ES, Lowne D, et al. (May 2006). "Probing a protein-protein interaction by in vitro evolution" [P]. Proceedings of the National Academy of Sciences of the United States of America. 103 (20): 7619–24. Bibcode:2006PNAS..103.7619T. doi:10.1073/pnas.0602341103. PMC 1458619. PMID 16684878.
  13. ^ May RD, Monk PD, Cohen ES, Manuel D, Dempsey F, Davis NH, et al. (May 2012). "Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the treatment of severe uncontrolled asthma". British Journal of Pharmacology. 166 (1): 177–93. doi:10.1111/j.1476-5381.2011.01659.x. PMC 3415647. PMID 21895629.
  14. ^ a b Human Antibody Molecules for Il-13, archived from the original on 8 February 2016, retrieved 26 July 2015
  15. ^ Jermutus L, Honegger A, Schwesinger F, Hanes J, Plückthun A (January 2001). "Tailoring in vitro evolution for protein affinity or stability". Proceedings of the National Academy of Sciences of the United States of America. 98 (1): 75–80. Bibcode:2001PNAS...98...75J. doi:10.1073/pnas.98.1.75. PMC 14547. PMID 11134506.
  16. ^ a b "Tralokinumab". Adis Insight. Springer Nature Switzerland AG. Archived from the original on 3 March 2016. Retrieved 20 February 2016.
  17. ^ Clinical trial number NCT01402986 for "A Phase 2b, Randomized, Double-blind Study to Evaluate the Efficacy of Tralokinumab in Adults With Asthma" at ClinicalTrials.gov
  18. ^ "Pipeline". MedImmune. Archived from the original on 7 August 2013. Retrieved 11 June 2013.
  19. ^ "Studies found for CAT-354". ClinicalTrials.gov. Archived from the original on 30 July 2013. Retrieved 11 June 2013.
  20. ^ "AstraZeneca enters licensing agreements with LEO Pharma in skin diseases". July 2016. Archived from the original on 3 October 2021. Retrieved 13 March 2017.
  21. ^ Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. (January 2019). "Treatment of atopic dermatitis with tralokinumab, an anti-IL-13 mAb". The Journal of Allergy and Clinical Immunology. 143 (1): 135–141. doi:10.1016/j.jaci.2018.05.029. PMID 29906525.
  22. ^ "LEO Pharma starts phase 3 clinical study for tralokinumab in atopic dermatitis". LEO Pharma (Press release). 1 July 2016. Archived from the original on 31 July 2019. Retrieved 31 July 2019.
  23. ^ a b "Adtralza: Pending EC decision". European Medicines Agency (EMA). 23 April 2021. Archived from the original on 23 April 2021. Retrieved 23 April 2021.
  24. ^ World Health Organization (2010). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 64". WHO Drug Information. 24 (3). hdl:10665/74577.
  25. ^ "Statement On A Nonproprietary Name Adopted By The USAN Council: Tralokinumab" (PDF). American Medical Association. Archived (PDF) from the original on 30 December 2021. Retrieved 4 July 2022.