Emerging Treatments for Psoriasis
Psoriasis affects 2% of the population and 20% of those affected have moderate to severe disease. Therefore, the demand for systemic treatment options in psoriasis persists and is likely to grow as patient expectations for disease clearance increase.1
In 2016, the FDA approved the first anti-IL-17 monoclonal antibody secukinumab (Cosentyx) for the treatment of psoriatic arthritis, the anti-IL-17 monoclonal antibody ixekizumab (Taltz) to treat moderate to severe plaque psoriasis, and expanded the indication for psoriasis treatment using the fusion-protein tumor necrosis factor (TNF) blocker etanercept (Enbrel) to include children aged 4 to 17 years.
The FDA approved brodalumab (Siliq), an anti-IL-17 receptor A (anti-IL-17RA) monoclonal antibody, to treat adults with moderate to severe plaque psoriasis in February 2017.2 By targeting IL-17RA, brodalumab antagonizes the IL-17 pathway and disrupts the biological activity of IL-17A, IL-17F, IL-17A/F heterodimers, and IL-25 (IL-17E).3 Approval was based on results from 3 multinational phase 3 trials involving 4373 participants enrolled in AMAGINE-1, AMAGINE-2, and AMAGINE-3.
The brodalumab phase 3 trials included a placebo-controlled 12-week induction phase, a 52-week open-label maintenance phase, and an open-label long-term extension. In each trial, the coprimary endpoints were the percentage of patients achieving a Psoriasis Area and Severity Index (PASI 75) response and a static Physician Global Assessment (PGA) of 0 or 1. However, AMAGINE-2 and AMAGINE-3 also included ustekinumab (Stelara) as an active comparator, and PASI 100 was used as the primary endpoint to distinguish brodalumab from ustekinumab responders at week 12.4 In AMAGINE-1, 83% of the participants achieved a PASI 75 response with brodalumab 210 mg every 2 weeks compared with 3% in the placebo group. In AMAGINE-2 and AMAGINE-3, 86% and 85% of participants achieved a PASI 75 response with brodalumab 210 mg every 2 weeks, respectively, compared with 8% and 6% in the placebo treatment arm.4
When compared with ustekinumab, patients treated with brodalumab were more likely to achieve a PASI 100 response at 12 weeks. In AMAGINE-2, 44% of participants treated with brodalumab 210 mg every 2 weeks obtained a PASI 100 response, while only 22% treated with ustekinumab and 1% in the placebo group obtained this same benchmark. Similarly, in AMAGINE-3, 37% of participants treated with brodalumab 210 mg every 2 weeks saw a PASI 100 improvement, while 19% of those treated with ustekinumab and 1% in the placebo group achieved this response.4 Based on results from these trials, subcutaneous brodalumab 210 mg on weeks 0, 1, and 2 followed by 210 mg every 2 weeks is the current FDA-approved dosage.2
The phase 3 brodalumab trials were terminated before completion due to an “unbalanced safety signal” regarding “suicide ideation and behavior.”5 Thus, long-term extension data for brodalumab is unavailable. Furthermore, although the package insert only lists Crohn disease as a contraindication, it is important to note that based on the observed risk of suicidal ideation and behavior, the package insert for brodalumab includes a boxed warning and availability will be restricted through a Risk Evaluation and Mitigation Strategy program.2
In May 2017, the FDA accepted the Biologics License Application (BLA) for tildrakizumab. The investigational drug targets the p19 subunit of IL-23. Tildrakizumab is an anti-IL-23p19 humanized IgG1 monoclonal antibody being evaluated for the treatment of moderate to severe plaque psoriasis. The BLA filing for tildrakizumab was submitted by Merck & Co. Inc.
Two phase 3 trials—reSURFACE 1 and reSURFACE 2—support the BLA filing. Both trials included a 12-week placebo-controlled phase and compared subcutaneous tildrakizumab 100 mg, tildrakizumab 200 mg, and placebo. However, while reSURFACE 1 was strictly placebo-controlled, reSURFACE2 included etanercept 50 mg twice weekly for 12 weeks as an active comparator. Dosing intervals for tildrakizumab in the trials involved 1 injection at baseline, 1 injection a month later, and then every 12 weeks thereafter. The coprimary endpoints were the proportion of patients achieving PASI 75 and PGA score of 0 or 1 at week 12. Secondary endpoints included PASI 90 and PASI 100 response rates.6
The reSURFACE 1 study showed that 64% of patients treated with tildrakizumab 100 mg and 62% of patients treated with tildrakizumab 200 mg achieved a PASI 75 response at week 12 compared with 3% in the placebo group. Findings from reSURFACE 2 demonstrated that 61% of patients treated with tildrakizumab 100 mg and 66% of patients treated with tildrakizumab 200 mg achieved a PASI 75 response at week 12 compared with 48% and 6% of patients treated with etanercept and placebo, respectively.6
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