This document provides information on the treatment of plaque psoriasis with the drug Ixekizumab (Taltz). It discusses that Ixekizumab is an injectable monoclonal antibody that binds to and inhibits the pro-inflammatory cytokine interleukin-17A (IL-17A). IL-17A plays a key role in the pathogenesis of psoriasis by stimulating keratinocyte proliferation and inflammatory responses. The document reviews clinical trial results demonstrating the safety and efficacy of Ixekizumab for plaque psoriasis. It also discusses two other drugs, Brodalumab and Secukinumab, that target the IL-17 pathway as treatment options for psoriasis.

1. Treatment for
management of plaque
psoriasis: Ixekizumab
(Taltz)
Presented by,
Goh Mei Ying
Lim Tze Shien
Tan Pei Ni

2. Introduction
Ixekizumab (Taltz)
 Injectable drug for the treatment of adult patients with moderate-to-severe plaque
psoriasis.
 A type of monoclonal antibody acts against the pro-inflammatory cytokine
interleukin-17A (IL-17A).
 IL-17A is secreted by Th17 cells which are differentiated from CD4+ cells.
 Th17 cells are situated at mucosal barriers.
 Function: Trigger pro-inflammatory signals => neutrophil mobilisation to site
of infection
 Keratinocytes and psoriatic plaques respond strongly to IL-17A.
 Contain high concentrations of Th17 cells => excessive production of IL-17A
=> excessive production of several inflammatory cytokines.
(Committee for Medicinal Products for Human Use (CHMP) 2016)
(Committee for Medicinal Products for Human Use (CHMP) 2016).

3. Figure 1: Taltz (Ixekizumab) (Haymarket Media 2016)

4. Figure 2: Taltz autoinjector Figure 3: Taltz prefilled syringe
(Drugs.com 2016) (Drugs.com 2016)

5. Figure 4: Injection site for Taltz (Drugs.com 2016)

6. Figure 5: Thigh injection using autoinjector
(Drugs.com 2016)
Figure 6: Thigh injection using prefilled syringe
(Drugs.com 2016)

7. What is Psoriasis ?
 An autoimmune disorder.
 Characterized by:
 redness, scaly patches, papules and plaques that usually itch
 Discolouration or pitting of the nails
 Often affects people between the ages of 15 and 35.
 family history of the disease
 Most common form : plaque psoriasis
 affects up to 90% of people with psoriasis
 Diagnosis:
 physical examination of the skin, scalp and nails
 skin biopsy => excessive growth and thickening of the epidermal layer
of the skin
(Committee for Medicinal Products for Human Use
(CHMP) 2016)
(Committee for Medicinal Products for Human Use (CHMP) 2016)

8. Figure 7: Signs & symptoms of psoriasis (Dr. Makkar 2014)

9. Ixekizumab (Taltz)
 In three randomized, placebo-controlled clinical trials, with a total of 3,866
patients with plaque psoriasis
 Taltz’s safety and efficacy were established
 achieved greater clinical response than placebo => skin that was clear or
almost clear
 assessed by Psoriasis Area Severity Index (PASI) score and static
Physician's Global Assessment (sPGA)
 Affects the immune system => increase the risks of contracting infections
 Medication Guide provided
 Serious hypersensitive responses
 Exacerbation of inflammatory bowel disease
 Common side effects:
 Upper respiratory infections
 Injection site reactions
 Nausea
 Fungal infections
(Food and Drug Administration 2016)
(Taltz 2016)

10. Properties of protein target
(Genecards.org n.d.)
Protein target: Interleukin-17A
Gene: IL17A gene
Cytogenetic band: 6p12.2 (Genecards.org n.d.)
 Pro-inflammatory cytokine
 Produced by activated T-cells
 Involved in inflammation and immune response
 Induce stromal cells to produce pro-inflammatory and hematopoietic
cytokines
 Preventing the host from infection (Drugbank.ca 2016)
 High level of IL-17A chronic inflammatory disease including
rheumatoid arthritis, psoriasis and multiple sclerosis (Onishi & Gaffen
2010)

11. Mechanism of action of
Ixekizumab
Ixekizumab  bind to IL-17A, inhibit the
interaction between IL-17A and its receptor
(IL-17RA)
 Hyper-proliferation of keratinocytes is driven by
cytokines from T cells
 Keratinocytes amplify the inflammatory response
 Psoriatic plaque  infiltration of activated T-cells
 Activated T cells: Th1, Th17 and Th22
 Activated T cells produce other cytokines
 IL-17A and IL-17F act on fibroblasts, keratinocytes
etc.
 High level of IL-17A and IL-17F  hyper-
proliferation of keratinocytes (Lønnberg, Zachariae
& Skov 2014).
Figure 8: Interleuking-17 in the pathogenesis of psoriasis
and targets of Brodalumab, Secukinumab and Ixekizumab
(Lønnberg, Zachariae & Skov 2014).

12. Development of related
analogs
Besides from Ixekizumab, two other drugs that targets IL-17A signalling pathway are
Brodalumab and Secukinumab (Leavitt 1996).
Adverse events include:
 Nasopharyngitis
 Upper respiratory tract
infection
 Nausea
 Headache
 Pain in the extremities
(Lønnberg, Zachariae & Skov
2014)
(Tse 2013)

13. Brodalumab
Inhibitors of IL-17RA
 Humanized chinese hamster ovary cell-
derived immunoglobulin G2(IgG2) anti-
IL-17RA (subunit of IL-17 receptor)
monoclonal antibody.
 Inhibit activities of IL-17A, IL-17F, IL-
17E/IL-25.
 Target a broader spectrum of IL-17
compare to Secukinumab and
Ixekizumab.
 Better efficiency
 Increased risk of adverse effects (less
specific) (Mease et al. 2014)
(Brodalumab 2016)

14. Secukinumab
Inhibitors of IL-17A
 A human anti-interleukin-17A
monoclonal antibody.
 Selectively binds and neutralizes IL-
17A, does not neutralize IL-17F.
 This specificity offers the potential of
fewer off target effects.
 Achievement of almost clear to clear
skin for the majority of patients (Mease
et al. 2015). (pharmacodia.com 2016)

15. Other related drugs under
development
 Interleukin-23 (IL-23) also a causative factor of psoriasis disease
(stimulates survival and proliferation of T-helper 17 cells).
 Overproduction of IL-23 by dendritic cells and keratinocytes stimulates
Th17 cells within the dermis to produce IL-17A and IL-22 (Fitch et al. 2007).
Guselkumab
 Injectable drug
 Monoclonal antibody
 Currently in clinical trials III
 Estimated to be in the market in year 2018
 Targets IL-23 specific intracellular and downstream signalling
 90% improvement in the Psoriasis Area Severity Index (McKee 2016)

16. Conclusion
Ixekizumab
 A type of monoclonal antibody
 Injectable drug
 Used for the treatment of moderate-to-severe plaque psoriasis
 Acts against pro-inflammatory cytokine IL-17A by binding to it, where it inhibits the interaction
between IL-17A & IL-17RA
Brodalumab
 Anti-IL-17RA monoclonal antibody
 Targets IL-17RA
 Inhibits activities of interleukin-17A, interleukin-17F, interleukin-17A/F, and interleukin-17E
Secukinumab
 Anti-IL-17A monoclonal antibody
 Selectively binds and neutralizes only IL-17A
 Specificity  fewer off target effects as compared to Brodalumab
Guselkumab
 Besides IL-17A, IL-23 also contributes to psoriasis by stimulating the production of IL-17.
Hence, Guselkumab, which targets IL-23, would be a potential drug for the treatment of psoriasis.

17. References
Brodalumab 2016, viewed 23 November 2016,
<http://www.pharmacodia.com/yaodu/html/v1/biologics/68dad4509908e9a208274a1ca8135221.html>.
Committee for Medicinal Products for Human Use (CHMP) 2016, Assessment report – Taltz, European Medicines
Agency, London, United Kingdom, viewed 4 November 2016,
<http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Public_assessment_report/human/003943/WC500205806.pdf>.
Dr. Makkar 2014, Psoriasis Homeopathic treatment, Dr. Makkar Family Clinic, viewed 18 November 2016,
<http://www.askdrmakkar.com/psoriasis_homeopathic_treatment.aspx>.
Drugbank.ca. 2016, DrugBank: Ixekizumab, viewed 7 November 2016,
<http://www.drugbank.ca/drugs/DB11569#targets>.
Drugs.com 2016, Taltz, viewed 18 November 2016, <https://www.drugs.com/pro/taltz.html>.
Fitch, E., Harper, E., Skorcheva, I., Kurtz, S. E., & Blauvelt, A. 2007, ‘Pathophysiology of Psoriasis: Recent
Advances on IL-23 and Th17 Cytokines’, Current Rheumatology Reports, 9(6), 461–467.
Food and Drug Administration 2016, FDA approves new psoriasis drug Taltz, Food and Drug Administration, United
States, viewed 4 November 2016,
<http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm491872.htm>.
Genecards.org. n.d., Genomic Location for IL17A Gene, viewed 7 November 2016, <http://www.genecards.org/cgi-
bin/carddisp.pl?gene=IL17A>.
Haymarket Media 2016, New Drug Product: Taltz, viewed 20 November 2016, <http://www.empr.com/new-drug-
product-taltz/slideshow/3126/>.
Leavitt, M. 1996, Popular advance online, viewed 9 November 2016, <https://www.psoriasis.org/advance/new-
psoriasis-drug-clears-skin-in-one-third-of-patients>.
Lønnberg, A. S., Zachariae, C., & Skov, L. 2014, ‘Targeting of interleukin-17 in the treatment of psoriasis’, Clinical,

18. References
McKee, S. 2016, Janssen’s guselkumab beats Humira in plaque psoriasis trial, viewed 9 November 2016,
<http://www.pharmatimes.com/news/janssens_guselkumab_beats_humira_in_plaque_psoriasis_trial_1151327>.
Mease, P.J., Genovese, M.C., Greenwald, M.W., Ritchlin, C.T., Beaulieu, A.D., Deodhar, A., Newmark, R., Feng, J.,
Erondu, N. & Nirula, A. 2014, ‘Brodalumab, an Anti-IL17RA monoclonal antibody, in Psoriatic arthritis’, New England
Journal of Medicine, 370(24), pp. 2295–2306. doi: 10.1056/nejmoa1315231.
Mease, P.J., McInnes, I.B., Kirkham, B., Kavanaugh, A., Rahman, P., van der Heijde, D., Landewé, R., Nash, P.,
Pricop, L., Yuan, J., Richards, H.B. & Mpofu, S. 2015, ‘Secukinumab inhibition of Interleukin-17A in patients with
Psoriatic arthritis’, New England Journal of Medicine, 373(14), pp. 1329–1339. doi: 10.1056/nejmoa1412679.
Onishi, R & Gaffen, S 2010, ‘Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease’,
IL-17-MEDIATED PATHOGENESIS I AUTOIMMUNE DISEASE, vol. 129, no. 3, pp. 331-321, viewed 13 November
2016, <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2826676/>.
pharmacodia.com 2016, Secukinumab, Pharmacodia Holding Ltd., viewed 23 November 2016,
<http://en.pharmacodia.com/web/drug/1_719.html>.
Taltz 2016, Important Safety Information, Eli Lilly and Company, USA, viewed 4 November 2016,
<https://www.taltz.com/>.
Tse, M.T. 2013, ‘IL-17 antibodies gain momentum’, Nature Reviews Drug Discovery, 12(11), pp. 815–816. doi:
10.1038/nrd4152.

19. ~ Thank you ~

20. ~ Q & A ~