Tralokinumab

(Heavy chain)
QVQLVQSGAE VKKPGASVKV SCKASGYTFT NYGLSWVRQA PGQGLEWMGW ISANNGDTNY
GQEFQGRVTM TTDTSTSTAY MELRSLRSDD TAVYYCARDS SSSWARWFFD LWGRGTLVTV
SSASTKGPSV FPLAPCSRST SESTAALGCL VKDYFPEPVT VSWNSGALTS GVHTFPAVLQ
SSGLYSLSSV VTVPSSSLGT KTYTCNVDHK PSNTKVDKRV ESKYGPPCPS CPAPEFLGGP
SVFLFPPKPK DTLMISRTPE VTCVVVDVSQ EDPEVQFNWY VDGVEVHNAK TKPREEQFNS
TYRVVSVLTV LHQDWLNGKE YKCKVSNKGL PSSIEKTISK AKGQPREPQV YTLPPSQEEM
TKNQVSLTCL VKGFYPSDIA VEWESNGQPE NNYKTTPPVL DSDGSFFLYS RLTVDKSRWQ
EGNVFSCSVM HEALHNHYTQ KSLSLSLGK
(Light chain)
SYVLTQPPSV SVAPGKTARI TCGGNIIGSK LVHWYQQKPG QAPVLVIYDD GDRPSGIPER
FSGSNSGNTA TLTISRVEAG DEADYYCQVW DTGSDPVVFG GGTKLTVLGQ PKAAPSVTLF
PPSSEELQAN KATLVCLISD FYPGAVTVAW KADSSPVKAG VETTTPSKQS NNKYAASSYL
SLTPEQWKSH RSYSCQVTHE GSTVEKTVAP TECS
(Disulfide bridge: H22-H96, H149-H205, H263-H323, H369-H427, H228-H’228, H231-H’231, L22-L87, L136-L195, H136-L213)

Tralokinumab

トラロキヌマブ (遺伝子組換え)

EU APPROVED, Adtralza, 2021/6/17

Antiasthmatic, Anti-inflammatory, Anti-IL-13 antibody

Tralokinumab is a human monoclonal antibody which targets the cytokine interleukin 13,^[1] and is designed for the treatment of asthma and other inflammatory diseases.^[2] Tralokinumab was discovered by Cambridge Antibody Technology scientists, using Ribosome Display, as CAT-354^[3] and taken through pre-clinical and early clinical development.^[4] After 2007 it has been developed by MedImmune, a member of the AstraZeneca group, where it is currently in Ph3 testing for asthma and Ph2b testing for atopic dermatitis.^[5][6] This makes it one of the few fully internally discovered and developed drug candidates in AstraZeneca’s late stage development pipeline.

Discovery and development

Tralokinumab (CAT-354) was discovered by Cambridge Antibody Technology scientists^[7] using protein optimization based on Ribosome Display.^[8] They used the extensive data sets from ribosome display to patent protect CAT-354 in a world-first of sequence-activity-relationship claims.^[7] In 2004, clinical development of CAT-354 was initiated with this first study completing in 2005.^[9] On 21 July 2011, MedImmune LLC initiated a Ph2b, randomized, double-blind study to evaluate the efficacy of tralokinumab in adults with asthma.^[10]

In 2016, MedImmune and AstraZeneca were developing tralokinumab for asthma (Ph3) and atopic dermatitis (Ph2b) while clinical development for moderate-to-severe ulcerative colitis and idiopathic pulmonary fibrosis (IPF) have been discontinued.^[9] In July of that year AstraZeneca licensed Tralokinumab to LEO Pharma for skin diseases.^[11]

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.^[12]

On 15 June 2017, Leo Pharma announced that they were starting phase III clinical trials with tralokinumab in atopic dermatitis.^[13]

Society and culture

Legal status

On 22 April 2021, the Committee for Medicinal Products for Human Use (CHMP) 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.^[14]

The applicant for this medicinal product is LEO Pharma A/S.

References

1. ^ 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.
2. ^ “Statement On A Nonproprietary Name Adopted By The USAN Council: Tralokinumab” (PDF). American Medical Association.
3. ^ 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.
4. ^ 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.
5. ^ “Pipeline”. MedImmune. Retrieved 11 June 2013.
6. ^ “Studies found for CAT-354”. ClinicalTrials.gov. Retrieved 11 June 2013.
7. ^ Jump up to:^a b Human Antibody Molecules for Il-13, retrieved 2015-07-26
8. ^ 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.
9. ^ Jump up to:^a b “Tralokinumab”. Adis Insight. Springer Nature Switzerland AG.
10. ^ 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
11. ^ “AstraZeneca enters licensing agreements with LEO Pharma in skin diseases”.
12. ^ 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.
13. ^ “LEO Pharma starts phase 3 clinical study for tralokinumab in atopic dermatitis”. leo-pharma.com. AstraZeneca. 1 July 2016.
14. ^ “Adtralza: Pending EC decision”. European Medicines Agency. 23 April 2021. Retrieved 23 April 2021.

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