When biotech and pharmaceutical companies develop a drug to treat one disease or condition, it is not unusual that the same drug, either alone or in combination with another drug, is proven to treat other conditions that may seem entirely unrelated. Many of the conditions that are classified under inflammation are close enough that they act as siblings or first cousins. It turns out that there may be hope that an oral treatment for chronic obstructive pulmonary disease (COPD) may have a use in a topical cream to treat atopic dermatitis and plaque psoriasis.
Arcutis Biotherapeutics, Inc. has begun pivotal Phase 3 clinical trials evaluating topical roflumilast cream, designated as ARQ-151, as a potential treatment for atopic dermatitis. The cream is a topical formulation of roflumilast to be used once daily and it is classified as potent and selective phosphodiesterase type 4 inhibitor. While COPD may seem a mile away from atopic dermatitis, Arcutis is also developing roflumilast cream as a treatment for plaque psoriasis.
Roflumilast already has a history on its own. It is already approved by the U.S. Food and Drug Administration to reduce the risk of exacerbations of chronic obstructive pulmonary disease, and it has been approved in the E.U. since 2010 and in the U.S. since 2011. According to Arcutis, the roflumilast cream is considered to potentially be the “Best in Class” topical PDE4 inhibitor. The topline data that will be eagerly awaited by the 19 million Americans with atopic dermatitis is expected to be seen in the second half of 2022.
It is estimated that more than 19+ million American have atopic dermatitis, which is the most common type of eczema. Arcutis has noted that at least 60% of that patient population are young children. The red and itchy rashes that come with it can cover significant areas of the body. Arcutis also notes that the current treatments often are not very effective, which brings a trade-off of safety and tolerability versus efficacy.
If roflumilast cream ultimately receives FDA approval it would be the first daily topical nonsteroidal treatment atopic dermatitis. Arcutis also noted that the cream would offer patients a more cosmetically-elegant and non-greasy formulation.
Roflumilast cream has already demonstrated in prior clinical trials as having a benign safety and tolerability profile versus many other topical treatments. One additional benefit that sets it apart from steroids is that roflumilast is expected to be safe for chronic use. The new parallel group and double-blind trials will be made of 650 patients each. It will be applied once per day in patients 6 years old and older with atopic mild to moderate atopic dermatitis that involves 3% or more of the body surface area.
These subjects will be randomized 2:1 to either roflumilast cream 0.15% or matching vehicle cream and the primary endpoint of both trials are to reach a score of ‘clear’ or ‘almost clear’ plus a 2-grade improvement from baseline at Week 4. There will also be multiple secondary endpoints such as itching and the proportion who attain at least a 75% reduction in the Eczema Area and Severity Index at Week 4. After completing INTEGUMENT-1 or -2, the subjects may then be eligible to enroll in a 12 month study evaluating the once daily roflumilast cream.
Arcutis, based in Westlake Village, California, is also planning a third Phase 3 study to evaluate roflumilast cream in subjects 2 to 5 years of age with mild to moderate atopic dermatitis. The company’s press release also indicates just how potent this topical roflumilast cream is: a potency of 25-fold to 300-fold than the two other FDA-approved PDE4 inhibitors.
PDE4 is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators. It has been implicated in a wide range of inflammatory diseases, including psoriasis, eczema, and COPD.
The topical roflumilast is considered Arcutis’ lead product candidate and the company believes it has the potential to revitalize the standard of care for plaque psoriasis, atopic dermatitis, scalp psoriasis, and seborrheic dermatitis. That’s quite a bit of inflammation targets covering millions of Americans.