Boxed warnings and restrictive labelling for Incyte’s atopic dermatitis topical Opzelura sets precedent for pipeline topical JAK inhibitors, says GlobalData

While GlobalData expects the approval of Opzelura (ruxolitinib) to be the first of many JAK inhibitors to enter the US market for the treatment of atopic dermatitis (AD), the leading data and analytics company notes that developers of these drugs need to find ways to overcome the FDA’s restrictive labelling.

Ramla Salad, Pharma Analyst at GlobalData, comments: “Opzelura’s labelling speaks volumes for what can be expected for other topical JAK inhibitors looking to enter the AD market. It is a shame that the drug was given the same box warning as other oral JAK inhibitors, despite it being a topical formulation, as there is a clear unmet need for better therapies targeting mild to moderate AD, and the FDA is merely creating barriers to their production.

The FDA’s warning is based on data from the oral JAK inhibitor Xeljanz (tofacitinib) in rheumatoid arthritis, and focuses on an increased risk of cardiovascular events, cancer, and serious infections such as tuberculosis. However, it is not just the warning,

Salad continues: “Opzelura’s labeling is also fairly restrictive. The drug is specifically indicated for the short-term treatment of mild-to-moderate AD in non-immunocompromised patients 12 years of age and older whose disease is inadequately controlled with available topical prescription therapies (or in whom those therapies cannot be used). In contrast, the label for Pfizer’s topical phosphodiesterase 4 inhibitor Eucrisa (crisaborole) is much broader, simply indicating the topical treatment for use in mild-to-moderate patients aged three months and older.

As well as limiting the drug’s use to patients who have failed other therapies, Opzelura’s label also advises that the drug is not to be used in combination with therapeutic biologics, other JAK inhibitors or potent immunosuppressants such as cyclosporine. This may be an important consideration for more moderate AD patients looking to use Opzelura.

Overall, the labeling significantly limits the target patient population that Opzelura can treat, meaning it will likely be considered a last line of therapy for the treatment-refractory of mild to moderate patients.

GlobalData believes that other topical JAK inhibitors in the pipeline for AD such as LEO Pharma’s delgocitinib and Pfizer’s brepocitinib should expect a similar label.

Salad explains: “It is possible that LEO Pharma may be able to leverage real-world evidence from Japan to support claims about delgocitinib’s long-term safety and efficacy. Additionally, LEO Pharma’s strategy of targeting delgocitinib to high-unmet-need patients with chronic hand eczema could help boost the drug’s position in the treatment paradigm – at least for this sub-population of AD patients.

“Meanwhile, Pfizer’s brepocitinib is targeting the same patient population as Opzelura, but via the TYK2 and JAK1 pathways. Brepocitinib has yet to begin Phase III development, and thus it remains to be seen whether targeting these specific JAKs will differentiate the product from Opzelura.”

As important as these safety concerns may be, key opinion leaders (KOLs) interviewed by GlobalData were far less worried about JAK inhibitor safety in the context of topical products. These experts expressed enthusiasm for topical JAK inhibitors, commenting on their excellent safety, tolerability and efficacy profiles.

More Media