Aiming to avoid Pfizer's Eucrisa failure, Arcutis wins FDA nod for Zoryve cream in psoriasis

Pfizer once harbored blockbuster hopes for Eucrisa to be the next big topical treatment for inflammatory skin diseases. But the ointment never gained traction thanks to side effects and reimbursement hurdles. Now, young biotech Arcutis Biotherapeutics is bringing along a new therapy that goes after the same drug target but with a very different product profile.

Arcutis’ cream drug, called roflumilast, just won FDA approval under the brand name Zoryve to treat plaque psoriasis, including in skin folds known as intertriginous areas, among patients 12 years of age and above. The green light covers all stages of disease from mild to severe without any limitations on duration of use. 

After years of commercial preparation, Arcutis will launch the steroid-free Zoryve cream immediately after Friday’s approval, CEO Frank Watanabe told Fierce Pharma in an interview ahead of the approval.

Lamenting “overly aggressive” pricing of existing topicals, Watanabe said Arcutis will price Zoryve at a wholesale acquisition cost of $825 per 60-g tube. That’s much lower than the $1,325-per-tube list price Dermavant has put on its newly FDA-approved rival psoriasis cream Vtama or the $1,950 sticker Incyte has for its topical atopic dermatitis drug Opzelura.

Arcutis set that price because insurance companies said it’s “a reasonable price” that they’re willing to reimburse without too many obstacles and restrictions, Watanabe said. “That’s why we think we’re going to be able to secure hopefully broad and high-quality coverage.”

Pfizer originally projected Eucrisa could reach over $2 billion in peak sales but didn’t spare it a separate line of its sales report in 2021. Unfavorable formulary placement and higher rebates in the face of cheap steroids are part of the reasons behind its commercial failure.

Arcutis has also put topical roflumilast’s sales potential across multiple indications at between $1.8 billion to $3.8 billion in 2030, according to Mizuho analysts. Both Eucrisa and Zoryve belong to the PDE4 inhibitor class, but, as Watanabe sees it, they are very different products.

First of all, Eucrisa, currently only approved for eczema, never worked in psoriasis. A higher concentration of the drug didn’t pass early safety tests for psoriasis, so its original developer Anacor Pharma—which was bought by Pfizer for $5.2 billion in 2016—lowered the dosing and moved to eczema, Watanabe recalled.

Even in its current form, Eucrisa causes a burning or stinging sensation, which has significantly limited its uptake.

Amgen has oral PDE4 inhibitor Otezla, which sold $2.2 billion in 2021. But Otezla could cause diarrhea and nausea to the tune of 17% for each side effect in clinical trials of plaque psoriasis.

Zoryve boasts an efficacy that’s “at least as good as” Otezla in psoriasis, but without the burning and stinging of Eucrisa, and has shown “hardly any” of the gastrointestinal side effects of Otezla, Watanabe said.

Across two clinical trials, DERMIS-1 and DERMIS-2, Zoryve achieved investigator-assessed treatment success in 40% of patients at Week 8 compared to around 6% to 7% for a dummy drug.

Doctors really like Zoryve’s strong safety profile, SVB Securities analysts recently noted after the FDA flagged safety concerns for JAK inhibitors, including Opzelura. In a survey SVB did last year, 84% of physicians expressed no concern over Zoryve’s safety profile, including 45% who called it encouraging.

What’s more, while both Eucrisa and Otezla are taken twice daily, Zoryve is a once-daily treatment. Eucrisa failed to win over patients also because of its greasy ointment texture, Watanabe noted, whereas Zoryve’s cream formulation means it can be absorbed quickly by the skin.

In the current psoriasis treatment landscape, novel biologics such as Novartis’ Cosentyx, Eli Lilly’s Taltz and AbbVie’s Skyrizi have demonstrated remarkable efficacy in psoriasis. Watanabe, who previously worked on the marketing of Enbrel at Amgen, said Zoryve isn’t positioned as a competitor to the biologics.

“We really see us as being complementary to—not competing with—the biologics,” the chief executive said.

Despite their stellar efficacy, only about 8% of psoriasis patients are actually on a biologic, while almost every patient is on a topical drug, Watanabe noted. Besides, biologics have shown they could get about 50% of psoriasis patients to completely normal skin. That leaves another 50% where Zoryve could come in to help clear out any leftover plaques, he added.

Zoryve also differentiates itself with a specific mention of treating skin folds on its label. These are sensitive areas where traditional steroids may cause additional side effects.

“Doctors have told us, 'that’s the first place I’m going to use Zoryve, because it’s so obvious and I don’t have any good options there,'” Watanabe said.

Other patients who have repeatedly cycled through steroids and vitamin D analogs, those that suffer from itch and those who are averse to steroids will likely be the first adopters of Zoryve, Watanabe said.

Still, Zoryve may face tough competition from Dermavant’s Vtama cream, an AhR agonist, which also comes with a fairly clean safety profile except for reports of hair follicle inflammation. In SVB’s survey, physician responses on efficacy, safety and future use were all more favorable for Vtama than for Zoryve.

Arcutis has been preparing for the launch for a long time. The company’s medical affairs team has been educating doctors for a year and a half, and it brought on its payer team a year ago. It has also hired half of its sales team, with the other half planned at approval.

The company is looking beyond psoriasis as well. Phase 3 trials of Zoryve in atopic dermatitis are expected to read out by the end of the year. A foam formulation of the drug recently returned positive results in a phase 3, and Arcutis now plans to file with the FDA early next year, Watanabe said.