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Clinical trial results suggest that monoclonal antibodies targeting the function of proinflammatory cytokine IL-17A in psoriasis may be significantly superior to other treatments.
The standard of care for the treatment of plaque psoriasis is being turned on its head by drugs coming onto the market that target interleukin-17 (IL-17) receptors. Based on results of many previous clinical trials, IL-17 appears to be a superior target than drugs that inhibit tumor necrosis factors (TNF inhibitors), such as Enbrel (etanercept). Now, new clinical trial results suggest that IL-17 may even be a superior target to drugs working on interleukin 12 (IL-12) and interleukin 23 (IL-23), which are the proteins of focus in drugs such as Johnson & Johnson’s Stelara (ustekinumab) and many investigational monoclonal antibodies (mAbs) in the pipeline. Stelara works by targeting IL-23 and IL-12, which reduces IL-17 indirectly.
Novartis stated on Mar. 23, 2015 that its drug Cosentyx (secukinumab) cleared skin in patients with psoriasis in 16 weeks-as measured by a response of 90 on the Psoriasis Area Severity Index (PASI) -better than Stelara (79% vs. 57.6%, respectively). In addition, completely clear skin (PASI 100) at week 16 was achieved by significantly more patients treated with Cosentyx than those receiving Stelara (44.3% vs. 28.4%, respectively).
While Cosentyx is the first and only IL-17A inhibitor currently approved for psoriasis, other manufacturers are also developing IL-17A therapies for psoriasis, such as Eli Lilly (ixekizumab) and Amgen/AstraZeneca (brodalumab). Ixekizumab is expected to be approved in the first half of 2015; Amgen and AstraZeneca are initiating global regulatory filings for brodalumab this year.
Enbrel is currently considered the standard of care to treat psoriasis and is the most commonly used drug among TNF inhibitors, according to a study by the Journal of Managed Care Pharmacy. Many existing psoriasis biologics, such as Humira (adalimumab), Remicade (infliximab), and Enbrel (etanercept), inhibit TNF-alpha signaling. Thus, barring any major adverse events, the efficacy results associated with anti-IL-17 medications may mean the reign of anti-TNF medications for the treatment of psoriasis may be coming to a close. Cosentyx is also in Phase III development for psoriatic arthritis (PsA) and ankylosing spondylitis (AS); joint regulatory applications for secukinumab in AS and PsA are planned for 2015.