Incyte’s JAK inhibitor cream clears second eczema trial

Incyte now has a pair of positive phase 3 trials for its topical formulation of JAK1/2 inhibitor ruxolitinib in atopic dermatitis or eczema, setting up regulatory filings for the new product later this year.

Ruxolitinib is already on the market in oral form under the Jakafi/Jakavi brand names as a treatment for myelofibrosis, a type of bone marrow cancer. The reformulation could open up a new and very large treatment category for the drug, as well as new territory for the JAK inhibitor class.

The cream met both the primary and secondary endpoints in the TRuE-AD1 trial involving adolescent and adult patients with atopic dermatitis, coming a month after the US biotech reported positive results from the TRuE-AD2 study.

In both trials, significantly more patients treated with ruxolitinib cream (0.75% or 1.5%) achieved Investigator’s Global Assessment Treatment Success (IGA-TS) than patients treated with a control non-medicated cream.

Success was defined as an IGA score of 0 (clear skin) or 1 (almost clear) with at least a two-point improvement from baseline after eight weeks.

In TRuE-AD1 50% of patients treated with ruxolitinib 0.75% and 54% of the 1.5% arm had an IGA-TS, depending on dose, compared to 15% of the control group. For TRuE-AD2, the rates were 39%, 51% and 7.6%, respectively

Around 50-60% of patients across the two trials achieved a 75% or greater improvement in symptoms based on the widely used Eczema Area and Severity Index (EASI) scale, versus 14% of those on the non-medicated cream.

The trials recruited patients with mild-to-moderate atopic dermatitis with consistent symptoms over at least two years. So if approved, ruxolitinib cream would address a less severely-affected population than new biologic agents such as Sanofi/Regeneron’s blockbuster Dupixent (dupilumab) antibody.

Its closest rival is likely to be Pfizer’s PDE-4 inhibitor Eucrisa (crisaborole) ointment, which was approved in the US in 2016, and generic corticosteroid creams that cause side effects like skin thinning when used over an extended period.

Eucrisa was billed as a potential $2bn-a-year blockbuster when it first launched, but has underperformed so badly that Pfizer took a $2.6bn impairment charge related to the product in its 2019 financial results, related to its $5.2bn acquisition of the drug’s developer Anacor Biopharma. Eucrisa’s sales were just $138m last year, down 7%.

Other competition could also be on the way. The oral JAK inhibitor market is split between drugs used to treat cancer, like Jakafi, and those used for inflammatory diseases such as rheumatoid arthritis.

The latter group includes Pfizer’s Xeljanz, (tofacitinib), Eli Lilly’s Olumiant (baricitinib) and AbbVie’s Rinvoq (upadacitinib), which have been approved for rheumatoid arthritis but are also in testing for other indications, including atopic dermatitis.

A potentially big advantage for Incyte with its topical formulation is lower systemic exposure to the active drug, as some of the oral JAK inhibitors carry boxed warnings about the risk of thrombotic side effects.

Incyte has said it intends to market ruxolitinib cream itself in the US if approved, but may seek partnerships in other territories such as Europe and Japan.