Ixekizumab

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Ixekizumab
Monoclonal antibody
Type Whole antibody
Source Humanized
Target IL-17A
Clinical data
Trade names Taltz
AHFS/Drugs.com taltz
Routes of
administration
Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 54–90%
Metabolism Presumably proteolysis
Biological half-life 13 days
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
Formula C6492H10012N1728O2028S46
Molar mass 146.2 kg/mol
 NYesY (what is this?)  (verify)

Ixekizumab (trade name Taltz) is an injectable drug for the treatment of autoimmune diseases. Chemically, it is a humanized monoclonal antibody.[1] The substance acts by blocking interleukin 17, reducing inflammation.[2]

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

Medical uses[edit]

Ixekizumab is used for the treatment of moderate to severe plaque psoriasis in adults.[2]

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.[2][3]

Contraindications[edit]

The drug is contraindicated for patients with certain infections such as active tuberculosis.[2]

Adverse effects[edit]

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%).[2]

Overdose[edit]

Up to fourfold doses have been given in studies without causing serious side effects.[2]

Interactions[edit]

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.[2]

Pharmacology[edit]

Mechanism of action[edit]

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.[2] This mechanism is similar to that of another anti-psoriasis antibody, brodalumab, which binds to the interleukin-17 receptor.[4]

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.[2]

Pharmacokinetics[edit]

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.[2]

Like other antibodies, ixekizumab is probably degraded by proteolysis. Its elimination half-life is 13 days.[2]

Chemistry[edit]

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.[1][5]

History[edit]

Clinical trials included a Phase II trial of patients with moderate to severe psoriasis,[4] and a Phase III open-label trial.[6] The drug was approved by the FDA on 22 March 2016 for the treatment of plaque psoriasis, under the trade name Taltz,[7] and by the European Medicines Agency on 25 April 2016 under the same trade name.[8]

The drug was launched in the US on 16 April 2016 and has been approved for use in the UK and is expected to launch on 1 July 2016.[9][needs update]

Research[edit]

As of 2016, ixekizumab is in Phase III clinical trials for the treatment of active psoriatic arthritis.[10]

References[edit]

  1. ^ a b "Statement On A Nonproprietary Name Adopted By The USAN Council: Ixekizumab" (PDF). American Medical Association. 
  2. ^ a b c d e f g h i j k Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. 
  3. ^ Klement, A (4 June 2016). "Taltz". Österreichische Apothekerzeitung (in German) (14/2016): 12. 
  4. ^ a b "Neue Antikörper in der Pipeline". Pharmazeutische Zeitung (in German) (12). 2012. 
  5. ^ "Assessment report: Taltz" (PDF). European Medicines Agency. 25 February 2016. p. 7. 
  6. ^ Clinical trial number NCT01624233 for "A Study in Japanese Participants With Moderate-to-Severe Psoriasis" at ClinicalTrials.gov
  7. ^ "FDA approves new psiorasis drug Taltz". Food and Drug Administration. 
  8. ^ "Taltz – EPAR summary for the public" (PDF). European Medicines Agency. April 2016. 
  9. ^ Design, inNottingham Web. "ixekizumab (Taltz) UKMi New Drugs Online Database". www.ukmi.nhs.uk. Retrieved 2016-06-12. 
  10. ^ Mease, P. J.; Van Der Heijde, D; Ritchlin, C. T.; Okada, M; Cuchacovich, R. S.; Shuler, C. L.; Lin, C. Y.; Braun, D. K.; Lee, C. H.; Gladman, D. D.; Spirit-p1 Study, Group (2016). "Ixekizumab, an interleukin-17A specific monoclonal antibody, for the treatment of biologic-naive patients with active psoriatic arthritis: Results from the 24-week randomised, double-blind, placebo-controlled and active (adalimumab)-controlled period of the phase III trial SPIRIT-P1". Annals of the Rheumatic Diseases: annrheumdis–2016–209709. PMID 27553214. doi:10.1136/annrheumdis-2016-209709.