Biologic Therapies Targeting the P19 subunit of IL-23

Three additional biologic mAbs that target the P19 subunit of IL-23 currently undergoing clinical trials for the treatment of moderate-to-severe plaque psoriasis are guselkumab (CNTO 1959 Janssen), tildrakizumab (MK-3222, Merck & Co.), and BI 655066 (AbbVie and Boehringer Ingelheim). 

Guselkumab is a fully human IgG1λ mAb that showed higher PGA scores at 16 weeks versus placebo in a phase 2 study. The score was 34% with 5mg dosing, 61% with 15mg, 79% with 50mg, 86% with 100mg, and 83% in the 200mg groups, compared with 7% for placebo. When compared with adalimumab, 58% of patients had a PGA score of 0 or 1, significantly lower than that observed with guselkumab at doses of 50, 100, and 200mg. In addition, PASI 75 was significantly higher versus placebo at 16 weeks for all doses of guselkumab: 44% with 5mg, 77% with 15mg, 81% with 50mg, 79% with 100mg, and 81% with 200mg compared with 5% for placebo. For those treated with adalimumab, 70% achieved PASI 75. Efficacy was demonstrated with guselkumab as early as 4 weeks after the first dose. Phase 3 trials are ongoing.4


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A randomized phase 2b clinical trial of tildrakizumab, a humanized KgG1κ mAb, found that at all doses, administered subcutaneously every 12 weeks (after two initial doses at weeks 0 and 4), PASI 75 was significantly higher for all doses versus placebo. At 5mg, PASI 75 was 33.3%; for 25mg, 64.4%; for 100mg, 66.3%; and for 200mg, 74.4%, compared with 4.4% for placebo. A low rate of relapse was observed after treatment cessation, with only 3.6% of patients who achieved PASI 75 at week 52 on any dose relapsing prior to week 72.4 A phase 3 study of tildrakizumab 100mg and 200mg versus etanercept and placebo is ongoing

BI 655066, a high affinity mAb,4 administered subcutaneously, has been shown in a phase 2 study to maintain PASI 90 after 9 months in 69% of patients compared with 30% percent on ustekinumab; for PASI 100, this was 43% for BI 655056 versus 15% for ustekinumab. Patients treated with BI 655056 had skin clearance at about 8 weeks with BI 655056 versus 16 weeks with ustekinumab, and for more than 2 months longer, ≥32 weeks versus 24 weeks, respectively. Common adverse events included common cold and headache.7 A randomized phase 3 trial of BI 655066 versus ustekinumab and placebo for maintenance use in moderate to severe plaque psoriasis is currently recruiting study participants.

Biologic therapies targeting IL-23 and IL-17 represent safe treatments for patients with moderate-to-severe plaque psoriasis and, based on study results showing many attain PASI 100, have the potential to offer greater efficacy than agents currently in use.

References: 

1. American Academy of Dermatology. Psoriasis. https://www.aad.org/media-resources/stats-and-facts/conditions/psoriasis. Accessed March 21, 2016.

2. Armstrong AW, Lynde CW, McBride SR, et al. Effect of ixekizumab treatment on work productivity for patients with moderate-to-severe plaque psoriasis: Analysis of results from 3 randomized phase 3 clinical trials. JAMA Dermatol. doi:10.1001/jamadermatol.2016.0269. Published online March 7, 2016.

3. Boehringer Ingelheim. BI 655066 versus ustekinumab and placebo comparators in a randomized double blind trial for maintenance use in moderate to severe plaque type psoriasis-2 (UltIMMa-2). Available at: https://clinicaltrials.gov/ct2/show/NCT02684357. Accessed March 21, 2016.

4. Campa M, Mansouri B, Warren R, Menter A. A review of biologic therapies targeting IL-23 and IL-17 for use in moderate-to-severe plaque psoriasis. Dermatol Ther (Heidelb). Published online December 29, 2015. doi:10.1007/s13555-015-0092-3.

5. Farahnik B, Beroukhim K, Zhu TH, et al. Ixekizumab for the treatment of psoriasis: A review of phase III trials. Dermatol Ther (Heidelb). Published online February 24, 2016. doi:10.1007/s13555-016-0102-0.

6. Merck Sharp & Dohme Corp. A 52-Week, Phase 3, Randomized, Active Comparator and Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222), Followed by an Optional Long-Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-011). Available at https://clinicaltrials.gov/ct2/show/NCT01729754. Accessed March 21, 2016.

7. Papp K, et al. 2015. Onset and duration of clinical response following treatment with a selective IL-23p19 inhibitor (BI 655066) compared with ustekinumab in patients with moderate-to-severe chronic plaque psoriasis. 24th European Academy of Dermatology and Venereology (EADV) congress, Copenhagen, Denmark, 7-11th October 2015.

8. U.S. Food and Drug Administration. TALTZ (ixekizumab). Indianapolis, IN: Eli Lilly and Company. 2016. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125521s000lbl.pdf. Accessed March 26, 2016.