As part of this year’s AAD, several speakers reported on on research-stage antipsoriatic agents, which showed promising results in phase 2 trials. Biologics and tyrosine kinase 2 inhibitors are among the drugs represented.
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In addition to the monoclonal antibody Risankizumab, which was approved this year, several clinical studies on the efficacy and safety of other substances are currently underway, with positive interim results.
Bimekizumab: good outcomes after 60 weeks
The results of the BE ABLE 1 and BE ABLE 2 extension studies indicate great potential of this monoclonal antibody for long-term maintenance therapy, as indicated in the presentation by Dr. Andrew Blauvelt, Oregon Medical Research Center [1]. Bimekizumab is a potent and selective neutralizer of IL-17A and IL-17F, two key proinflammatory cytokines.
In the 12-week double-blind placebo-controlled phase 2 BE ABLE study 1, bimekizumab resulted in rapid and substantial clinical improvement in moderate to severe plaque psoriasis with a safety profile comparable to previous studies of this agent [2]. Subjects were randomly assigned to experimental conditions and received bimekizumab subcutaneously at 4-week intervals at varying doses: 64 mg, 160 mg, 160 mg with dose escalation to 320 mg, 320 mg, 480 mg, or placebo. Primary endpoint was ≥90% reduction in Psoriasis Area Severity Index (PASI90) at week 12.
Jeffrey Weinberg, M.D., Icahn School of Medicine, reported phase 2b data for bimekizumab. 50-60% of the highest dose groups achieved PASI 100 at week 12 [2]. In the BE ABLE 2 extension study (n=217), bimekizumab performed well in maintaining complete or near-complete lesion clearance in psoriasis patients over a 60-week period [3]. 80 to 100% of responders (all doses) to BE ABLE 1 showed maintenance of nearly 90% symptom reduction (PASI90) (Fig. 1). These positive results are currently the longest survey period. Phase 3 comparative studies of bimekizumab in psoriasis are being conducted based on these results.
BMS-986165: dose-related PASI-75 outcomes.
Leon Kircik, M.D., Icahn School of Medicine Mount Sinai, New York, presented data from BMS-986165, a tyrosine kinase-2 inhibitor, which is classified as a Janus kinase (JAK) [4]. Tyrosine kinase-2 pathways play a mediating role for cytokines involved in the pathophysiology of psoriasis.
A double-blind phase 2 study (n=267) was conducted to evaluate the efficacy of BMS-986165 in tablet form in adults with moderate to severe psoriasis. Subjects were randomly assigned to placebo or one of the verum conditions. After 12 weeks, 75% of patients at a dose of 12 mg daily showed min. 75% reduction in PASI score (primary endpoint). In the subgroup with a dose of 6 mg twice daily, 67% achieved this target value; in that with a dose of 3 mg twice daily, 69%; and in that with 3 mg once daily, 39%. The differences from placebo were significant in each case (p<0.001).
The safety profile of JAK inhibitors has not been clearly established. Further long-term data are needed to investigate whether this class of compounds is associated with a statistically increased risk of infection and malignancy [5–7].
Source: AAD, Annual Meeting 2019, Washington (USA)
Literature:
- AAD: Annual Meeting February 28 – March 5, 2019, Washington, Dr. Andrew Blauvelt, Oregon Medical Research Center.
- Papp KA, et al: Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol. 2018; 79(2): 277-286.e10.
- Blauvelt A, et al: Dual Neutralisation Of Interleukin (Il)-17a And Il-17f With Bimekizumab In Moderate-To-Severe Plaque Psoriasis: 60-Week Results From A Randomised, Double-Blinded, Phase 2b Extension Study. https://ard.bmj.com/content/78/Suppl_2/1834.1
- AAD: Annual Meeting February 28 – March 5, 2019, Washington, Dr. Leon Kircik, Icahn School of Medicine Mount Sinai, New York.
- Winthrop KL: The emerging safety profile of JAK inhibitors in rheumatic disease. Nat Rev Rheumatol 2017; 13(4): 234-243.
- Verden A, Dimbil M, Kyle R, et al: Analysis of Spontaneous Postmarket Case Reports Submitted to the FDA Regarding Thromboembolic Adverse Events and JAK Inhibitors. Drug Saf 2018; 41: 357-361; 41(4): 357-361.
- Papp K, et al: Phase 2 Trial of Selective Tyrosine Kinase 2 Inhibition in Psoriasis. N Engl J Med 2018; 379: 1313-1321.
DERMATOLOGIE PRAXIS 2019; 29(5): 38 (published 10/10/19, ahead of print).
