Group 4 Oral Presentation Slides

1. PHA60104 DRUG DISCOVERY &
DEVELOPMENT
USTEKINUMAB
Treatments for Management of Psoriasis

2. Group members
Chia Kay Veng 0315349
Liew Lee Bing 0321961
Muhammad Haris Ursilaniew 0325909
Sathiavani A/P Arishkrinan 0316271
Tan Kian Leong 0323426

3. Introduction
• Known as Stelara and CNTO 1275
• Plaque psoriasis and psoriatic arthritis
• p40 interleukin-12 (IL-12) and interleukin-23 (IL-23) subunit
• Functions :
- inhibition of IL-12 and IL-23- mediated signalling
- downstream cytokine production
- inhibition of cellular activation
• Usually given as syringe and vial
• Crucial to be given according to a fixed schedule.

4. Properties of Protein Target
• IL-12 also known as the cytotoxic lymphocyte maturation factor (CLMF) or natural killer
stimulatory factor (NSFK) is a disulphide- linked heterodimeric (p40+p35) cytokine. IL-12 are
produced by monocytes, macrophages and dendritic cells when pathogens interact with the T-
cells (Ebioscience.com 2016)
• IL-23 is also a disulphide-linked heterodimer (p40+p19) secreted by activated dendritic cells
and macrophages (Ebioscience.com 2016).

5. Mode of Mechanism
• Binds specifically to IL-12 (Interleukin 12) and IL-23 (Interleukin 23) which are responsible in the inflammatory
and immune responses, such as activation of NK (natural killer) cells and T-cell + CD4 activation and
differentiation (RxList 2016).
• Interaction between IL-12 and IL-23 with IL-12Rβ1, a cell-surface receptor chain, was disrupted therefore
mechanism that are mediated by these 2 interleukins were disrupted.ustekinumab directed against naturally
occurring proteins interleukin 12 and interleukin 23, that regulate the immune system and immune mediated
disorders (Reddy et al. 2007).
• Activation of proliferation in the cell, activation of IFN gamma and activate cell cytotoxicity can be done by
these IL-12which contributes highly to the immune responses (Ebioscience.com 2016).
• The IL-23 regulates the Th17 function and cell proliferation which plays a role in the innate and adaptive
immunity (Ebioscience.com 2016).

6. Development of Derivatives
In 21st January 2015, Cosentyx (secukinumab) was approved to treat adults with moderate-to severe
plaque psoriasis (U.S. Food & Drug Administration 2015).
Secukinumab
- An antibody which binds to a protein interleukin (IL) – 17A (Langley et al. 2014).
- Significantly improves patient-reported itching, pain and scaling in adults with moderate to
severe psoriasis (Strober et al. 2016)
- 44.3% : 24.4% of Cosentyx (secukinumab) : Stelara (ustekinumab) at week 16 reach completely
clear skin (Hilton 2015).
- Superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and
improving health-related quality of life with a comparable safety profile over 16 weeks (Thaçi et
al. 2015).

7. Side Effects
• Psoriatic arthritis, the common side effects are nausea and dental infections.
• Cold-like symptoms such as runny nose and sore throat.
• Fatigueness, diarrhea and skin rashes.
• Bruising, itching and swelling of the skin.
• Arthralgia
• Immunosuppression, or a weakened immune system.
• Increased risk of infections such as tuberculosis
• Serious effects include reverse posterior leukoencephalopathy syndrome (RPLS)
(Cunha 2016)

8. Future Development
• Shows promising effects for immune-mediated inflammatory diseases (IMID) such as Crohn’s
disease (Jnj 2016).
• Ustekinumab is also in the Phase II study to evaluate its efficacy in treating sarcoidosis.

9. Conclusion
➔ Not only effective but as well safe
➔ Further studies and researches
- to expose the efficacy and side effect statues
- comparison of both Consentyx and Stelara

10. ReferencesCunha, JP 2016, ‘Sterela Side Effect Centre’, Common Side Effects Of Stelara
Injection (Ustekinumab) Drug Center - Rxlist., viewed 17 November 2016,
<http://www.rxlist.com/stelara-side-effects-drug-center.htm>
Ebioscience.com. (2016). IL-12 Overview. [online] Available at:
http://www.ebioscience.com/knowledge-center/antigen/il-12.htm [Accessed 24 Nov.
2016].
Dermatology Times. (2016). Secukinumab vs. Ustekinumab. [online] Available at:
http://dermatologytimes.modernmedicine.com/dermatology-
times/news/secukinumab-vs-ustekinumab?page=full [Accessed 24 Nov. 2016].
Jnj.com. 2016, FDA Approves STELARA® (Ustekinumab) for Treatment of Adults
With Moderately to Severely Active Crohn’s Disease | Johnson & Johnson, viewed
20 November 2016, <https://www.jnj.com/media-center/press-releases/fda-
approves-stelara-ustekinumab-for-treatment-of-adults-with-moderately-to-severely-
active-crohns-disease>
Langley, R, Elewski, B, Lebwohl, M, Reich, K, Griffiths, C, Papp, K, Puig, L,
Nakagawa, H, Spelman, L, Sigurgeirsson, B, Rivas, E, Tsai, T, Wasel, N, Tyring, S,
Salko, T, Hampele, I, Notter, M, Karpov, A, Helou, S & Papavassilis, C 2014,
'Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials', New England
Journal of Medicine, vol. 371, no. 4, pp. 326-338.
PMG Research 2016, 'Plaque Psoriasis – comparing secukinumab (Cosentyx®) with
ustekinumab (Stelara®) Clinical Trial in Charlotte, NC', viewed 14 November 2016,
<https://www.pmg-research.com/studies/facility/charlotte/plaque-psoriasis-
comparing-secukinumab-cosentyx-with-ustekinumab-stelara/>.
Psoriasis.org. (2016). Psoriasis types: Plaque Psoriasis | National Psoriasis Foundation. [online]
Available at: https://www.psoriasis.org/about-psoriasis/types/plaque [Accessed 24 Nov. 2016].
Reddy, M, Davis, C, Wong, J, Marsters, P, Pendley, C & Prabhakar, U 2007, 'Modulation of CLA,
IL-12R, CD40L, and IL-2Rα expression and inhibition of IL-12- and IL-23-induced cytokine
secretion by CNTO 1275', Cellular Immunology, vol. 247, issue 1, pp. 1-11.
RxList. 2016, Stelara Injection (Ustekinumab) Drug Information: Clinical Pharmacology -
Prescribing Information at RxList., viewed 17 November 2016, <http://www.rxlist.com/stelara-
drug/clinical-pharmacology.htm>
Strober, B, Sigurgeirsson, B, Popp, G, Sinclair, R, Krell, J, Stonkus, S, Septe, M, Elewski, B,
Gottlieb, A, Zhao, Y, Tran, M, Karpov, A, McLeod, L, Mordin, M, Papavassilis, C, Nyirady, J &
Lebwohl, M 2016, 'Secukinumab improves patient-reported psoriasis symptoms of itching, pain,
and scaling: results of two phase 3, randomized, placebo-controlled clinical trials', International
Journal of Dermatology, vol. 55, no. 4, pp. 401-407.
Thaçi, D, Blauvelt, A, Reich, K, Tsai, T, Vanaclocha, F, Kingo, K, Ziv, M, Pinter, A, Hugot, S, You,
R & Milutinovic, M 2015, 'Secukinumab is superior to ustekinumab in clearing skin of subjects with
moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial', Journal of the
American Academy of Dermatology, vol. 73, no. 3, pp. 400-409.
U.S. Food & Drug Administration 2015, FDA approves new psoriasis drug Cosentyx, viewed 16
November 2016,
<http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430969.htm>.