Analyst Notes: Can new targeted treatments transform the treatment of moderate-to-severe atopic dermatitis?

As Dupixent (dupilumab; Regeneron Pharmaceuticals/Sanofi) and Eucrisa (crisaborole; Pfizer) gain traction in the atopic dermatitis treatment paradigm, older, more toxic immunosuppressant treatment options are likely lose ground. But as the market evolves, and more treatments are approved, how important will clinical and commercial differentiation become?

Key opinion leaders (KOLs) interviewed by FirstWord for a new report titled Atopic Dermatitis: KOL Insight are optimistic about the future of the atopic dermatitis treatment landscape, but opine that with more targeted options on the horizon, effective patient selection will become increasingly important.

In the near-term, and notwithstanding minor concerns about the product's safety profile, KOLs suggest that Dupixent is likely to become the gold standard in moderate-to-severe patients, based on impressive efficacy data from the global LIBERTY AD clinical programme, a programme that included three randomised Phase III pivotal trials (SOLO 1, SOLO 2 and CHRONOS). The only reservation some KOLs have about Dupixent is the higher incidence of injection-site reactions and conjunctivitis.

"We're really excited about dupilumab. It's the first biologic that's actually showing value, and showing a lot of value." - US Key Opinion Leader

With regard to Eucrisa, KOLs have mixed views on the potential for this product. Some KOLs argued that Eucrisa's safety profile represents a significant advantage over topical steroids, while others highlight the drug's potential for treating sensitive areas such as the face, where topical steroid treatment may be deemed undesirable.

"We will use crisaborole in patients who don't respond to standard therapies, and also the patients who show some contraindication to the use of corticosteroids or calcineurin inhibitors." - European Key Opinion Leader

Moving further into the future, KOLs wonder if AstraZeneca/Leo Pharma's tralokinumab (an anti-IL-13 mAb currently in Phase III trials) and Dermira's lebrikizumab (an anti-IL-13 mAb recently licensed by Dermira from Roche) are sufficiently different to Dupixent (and themselves) to carve out a place in the treatment paradigm?

Similar concerns were also raised about mepolizumab (GlaoxSmithKline's anti-IL-5 mAb already licensed as a treatment for severe asthma) and nemolizumab (an anti-IL-31 mAb being developed by Galderma and Chugai). While these mAbs target different cytokines, which option will be the most appealing, and will each of these treatment options be able to carve out a niche for themselves based on their respective mechanisms of action?

"I don't know that increases in IL-5 are really driving atopic dermatitis. It's not something we pay a lot of attention to, and from a theoretical standpoint it may not be playing a role at all, so mepolizumab wouldn't be at the top of my list as something I'd be interested in." - US Key Opinion Leader

JAK inhibitors, also in approved and in development for a range of other inflammatory conditions (including psoriasis, rheumatoid arthritis and ulcerative colitis), may provide alternatives for treating atopic dermatitis, but safety concerns could limit uptake. With several JAK inhibitors in development, R&D investment in this category is high, so oral dosing may be sufficient to support clinical adoption.

"My biggest concern about the JAK pathway is that it’s a much broader biological pathway compared to the IL-4 and IL-13, which I consider to be a lot more specific to help in terms of dermatitis. I think they could be good for non-responders to IL-4/IL-13 axes inhibition." - US Key Opinion Leader

As the market grows, differentiation within the atopic dermatitis treatment landscape is likely to become increasingly challenging. Several clinical and commercial tactics are available to companies in order to differentiate themselves. The question becomes, are these tactics enough? As physicians become more selective, and payers become less willing to pay, which tactics will become more influential in the future?

For companies operating in the atopic dermatitis market in Europe and the US, Atopic Dermatitis: KOL Insight is a must read. The report provides actionable insights and commentary on some of the most critical issues in the atopic dermatitis market, and provides perspectives on pipeline therapies and their potential in a rapidly increasing market. The report also discusses how treatment paradigms could change in atopic dermatitis. For more information, please click here.

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