Ixekizumab

Ixekizumab, sold under the brand name Taltz, is an injectable drug for the treatment of autoimmune diseases. Chemically, it is a form of a humanized monoclonal antibody.[4] The substance acts by binding interleukin 17A and neutralizing it, reducing inflammation.[5][6]

Ixekizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized
TargetIL-17A
Clinical data
Pronunciationix-ee-KIZ-ue-mab[1]
Trade namesTaltz
AHFS/Drugs.comMonograph
MedlinePlusa616025
License data
Pregnancy
category
  • AU: C [2]
  • US: N (Not classified yet) [2]
    Routes of
    administration    		Subcutaneous injection
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • UK: POM (Prescription only) [3]
    • US: ℞-only
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    Bioavailability54–90%
    MetabolismPresumably proteolysis
    Elimination half-life13 days
    Identifiers
    CAS Number
    DrugBank
    ChemSpider
    • none
    UNII
    KEGG
    ChEMBL
    Chemical and physical data
    FormulaC6492H10012N1728O2028S46
    Molar mass146192.34 g·mol−1
     NY (what is this?)  (verify)

    The drug was developed by Eli Lilly and Co. and is approved for the treatment of plaque psoriasis in Europe and the US.[7][8]

    Medical uses

    In the United States, ixekizumab is approved for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy, active psoriatic arthritis, and active ankylosing spondylitis.[9] In Europe it is approved for the treatment of moderate-to-severe plaque psoriasis[7] and as a second-line therapy for active psoriatic arthritis.[5]

    In studies, the drug reduced the Psoriasis Area and Severity Index by at least 75% (PASI75) in 82–89% of patients during the first three months of treatment (depending on the dosing scheme), and 40% of patients experienced a complete absence of psoriasis symptoms (PASI100). In the placebo group, PASI75 was reached in 4% of patients, and PASI100 in none; in the group of patients receiving etanercept, an older anti-psoriasis drug, PASI75 was reached in 48%. Until the 60th study week, 11–44% of ixekizumab treated patients relapsed (again, depending on the dosing scheme), as compared to 84% under placebo.[5][10]

    In December 2017, the US Food and Drug Administration (FDA) approved it for active psoriatic arthritis.[11]

    Contraindications

    The medication is contraindicated for patients with certain infections such as active tuberculosis.[5]

    Adverse effects

    In studies, ixekizumab increased the rate of infections (27% of ixekizumab treated patients, compared to 23% under placebo), including severe ones (0.6% versus 0.4% under placebo). Other common side effects included injection site pain (13–17% versus 3%), oropharyngeal pain (1%) and nausea (1–2%).[5]

    Overdose

    Up to fourfold doses have been given in studies without causing serious side effects.[5]

    Interactions

    No interaction studies have been done. Ixekizumab and interleukin 17 are not known to interact with cytochrome P450 (CYP) liver enzymes. Since inflammation suppresses CYP activity, it is theorized that ixekizumab could neutralize this effect and lower blood plasma concentrations of drugs that are metabolized by CYP enzymes, such as warfarin.[5]

    Pharmacology

    Mechanism of action

    Ixekizumab binds to interleukin 17 (IL-17), a pro-inflammatory cytokine, and blocks its action. Among other things, IL-17 stimulates proliferation and activation of keratinocytes in the skin.[5] This mechanism is similar to that of another anti-psoriasis antibody, brodalumab, which binds to the interleukin-17 receptor.[12]

    The antibody has affinity to the homodimer IL-17A and the heterodimer IL-17A/F, but not to other members of the interleukin 17 family.[5]

    Pharmacokinetics

    After subcutaneous injection, ixekizumab has a bioavailability of 54–90%. Highest blood plasma concentrations are reached after four to seven days after a single dose. With the usual dosing scheme (loading plus a dose every two weeks), steady state concentrations are reached in the eighth week on average.[5]

    Like other antibodies, ixekizumab is probably degraded by proteolysis. Its elimination half-life is 13 days.[5]

    Chemistry

    Ixekizumab is a complete monoclonal antibody of the subclass IgG4, consisting of two light chains and two heavy chains linked by disulfide bridges. Both heavy chains are glycosylated at the asparagine in position 296. In the hinge region, a serine is replaced by a proline to reduce formation of half-antibodies and heterodimers in the manufacturing process. The terminal lysine found in wild-type IgG4 is removed. The antibody is produced in Chinese hamster ovary cells.[4][13]

    History

    Clinical trials included a Phase II trial of patients with moderate to severe psoriasis,[12] and a Phase III open-label trial.[14] The drug was approved by the US Food and Drug Administration (FDA) on March 22, 2016 for the treatment of plaque psoriasis, under the trade name Taltz,[15] and by the European Medicines Agency (EMA) on April 25, 2016 under the same trade name.[7]

    The drug was launched in the US on April 16, 2016, and was approved for use in the UK in the same year.[16]

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    References
    1. "12 Difficult-to-Pronounce Drug Names". pharmacytimes.com. Pharmacy Times. 7 February 2018. Retrieved 22 March 2018.
    2. "Ixekizumab (Taltz) Use During Pregnancy". Drugs.com. 27 November 2019. Retrieved 27 March 2020.
    3. "Taltz 80 mg solution for injection in pre-filled syringe - Summary of Product Characteristics (SmPC)". (emc). 21 August 2019. Retrieved 27 March 2020.
    4. "Statement On A Nonproprietary Name Adopted By The USAN Council: Ixekizumab" (PDF). American Medical Association.
    5. Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
    6. Cai Y, Fleming C, Yan J (July 2013). "Dermal γδ T cells--a new player in the pathogenesis of psoriasis". International Immunopharmacology. 16 (3): 388–91. doi:10.1016/j.intimp.2013.02.018. PMID 23499509.
    7. "Taltz EPAR". European Medicines Agency (EMA). 2 May 2016. Retrieved 27 March 2020.
    8. "Taltz (ixekizumab) Injection". U.S. Food and Drug Administration (FDA). 3 May 2016. Retrieved 27 March 2020.
    9. "Taltz- ixekizumab injection, solution". DailyMed. 23 August 2019. Retrieved 27 March 2020.
    10. Klement A (4 June 2016). "Taltz". Österreichische Apothekerzeitung (in German) (14/2016): 12.
    11. "FDA approves Taltz for psoriatic arthritis in adults
    12. "Neue Antikörper in der Pipeline". Pharmazeutische Zeitung (in German) (12). 2012.
    13. "Assessment report: Taltz" (PDF). European Medicines Agency. 25 February 2016. p. 7.
    14. Clinical trial number NCT01624233 for "A Study in Japanese Participants With Moderate-to-Severe Psoriasis" at ClinicalTrials.gov
    15. "FDA approves new psoriasis drug Taltz". U.S. Food and Drug Administration (FDA) (Press release). 22 March 2016. Retrieved 27 March 2020.
    16. Design, inNottingham Web. "ixekizumab (Taltz) UKMi New Drugs Online Database". www.ukmi.nhs.uk. Retrieved 12 June 2016.
    • "Ixekizumab". Drug Information Portal. U.S. National Library of Medicine.
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