As roflumilast cream charts a new course in plaque psoriasis, developer Arcutis Biotherapeutics is already eyeing the next stop on the drug’s immuno-dermatology odyssey.
Tuesday, Arcutis said roflumilast cream 0.15%—a lower dose than the 0.3% formulation approved in late July as Zoryve—aced its primary endpoint and all secondary endpoints in a phase 3 study in patients 6 and older with mild to moderate atopic dermatitis.
To meet the study’s main goal, roflumilast cream had to help a certain number of patients score "clear" or "almost clear" on an investigator eczema assessment. The drug also needed to deliver a 2-grade improvement from baseline on the investigator eczema assessment scale at the trial’s 4-week mark.
In Arcutis’ 654-subject Integument-1 trial, roflumilast cream helped 32% of patients meet those primary endpoint metrics, versus 15.2% of patients who received a dummy cream. The drug also charted “rapid and statistically significant improvements” compared with the control cream on “all” secondary endpoints, the company said in a release. Among those auxiliary targets, roflumilast cream helped 43.2% of patients curb the range and severity of their eczema by 75% at week 4. Just 22% of patients on the control cream hit the mark on that particular endpoint.
The trial forms one-half of a pair of “identically designed” late-stage trials, Arcutis explained. Results from the study’s twin, Integument-2, are due by year-end. Should that trial’s results be positive too, Arcutis plans to file an FDA application for roflumilast cream 0.15% to treat kids and adults with eczema in 2023.
Roflumilast cream is a non-steroidal topical phosphodiesterase-4 (PDE4) inhibitor. Approved in plaque psoriasis this summer as Zoryve, Arcutis’ med is a novel, topical formulation of the same active ingredient in AstraZeneca’s oral chronic obstructive pulmonary disease (COPD) drug Daliresp, which comes in tablets.
The drug is also in the same class as Pfizer’s fallen blockbuster prospect Eucrisa, which has failed to live up to the company’s blockbuster sales expectations after roughly 6 years on the market. Pfizer’s commercial failure can be blamed, in part, on unfavorable formulary placement and higher rebates in the face of cheap generics.
Roflumilast, for its part, could generate sales between $1.8 billion to $3.8 billion by 2030 across multiple indications, Arcutis has said, according to Mizuho analysts.
Citing a competitive price tag, a clean side effect profile and convenient dosing, Arcutis says roflumilast cream has an edge over rivals Eucrisa and Incyte's Opzelura, plus Amgen’s PDE4 inhibitor Otezla, which garnered $2.2 billion in 2021.
Still, Zoryve is destined to lock horns with Dermavant’s AhR agonist Vtama cream, which also boasts a fairly clean safety profile. In a 2021 SVB Securities survey, physician responses on efficacy, safety and future use were all more favorable for Vtama than for Zoryve.
After years of commercial preparation, Arcutis launched Zoryve in August, a little more than a week after the therapy’s FDA nod. Around the same time, Arcutis drew down $125 million from its loan facility and ginned up a further $161.7 million through a public stock offering. That left Arcutis with around $570 million to support Zoryve’s commercialization, plus its pipeline programs.
Elsewhere, roflumilast nabbed another clinical victory in September, this time as a 0.3% foam being tested in seborrheic dermatitis. Results from the late-stage STRATUM study found more than 80% of patients on roflumilast foam achieved meaningful improvements to their skin disease on an investigator global assessment versus 59.2% of patients on a placebo cream.
The chronic inflammatory condition seborrheic dermatitis affects more than 10 million people in the U.S., according to Arcutis’ estimates. The condition leads to the formation of red patches on the skin that are marked by “large, greasy, flaking yellow-gray scales and persistent itch,” Arcutis has said.
Arcutis aims to submit roflumilast foam for FDA approval in seborrheic dermatitis in the first quarter of 2023.