Study met the primary endpoint and key secondary endpoints, consistent with positive topline results from the INTEGUMENT-1 trial released in November
For the primary endpoint, 28.9% of individuals treated with roflumilast cream 0.15% achieved Investigator Global Assessment (IGA) Success compared to 12.0% of individuals treated with vehicle (P<0.0001)
42.0% of individuals treated with roflumilast cream 0.15% achieved a 75% improvement in Eczema Area and Severity Index (EASI-75) and 30.2% achieved a clinically meaningful reduction in itch at Week 4
Roflumilast cream was well tolerated and demonstrated a favorable safety and tolerability profile
Company to host a conference call to discuss results today at 8:30 a.m. ET

WESTLAKE VILLAGE, Calif., Dec. 12, 2022 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (NASDAQ:ARQT), an early commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced positive topline results from its INTEGUMENT-2 pivotal Phase 3 trial of roflumilast cream 0.15%, a once-daily, non-steroidal topical phosphodiesterase-4 (PDE4) inhibitor, in adults and children 6 years and older with mild to moderate atopic dermatitis (AD). The study met its primary endpoint, with 28.9% of individuals treated with roflumilast cream 0.15% achieving IGA Success, defined as a validated Investigator Global Assessment – Atopic Dermatitis (vIGA-AD) score of ‘clear' or ‘almost clear' plus a 2-grade improvement from baseline at Week 4, compared to 12.0% of individuals treated with vehicle (P<0.0001).

"Atopic dermatitis, a common condition in children through adults, is a chronic disease characterized by intense, persistent itching and eczematous rashes, that can greatly impact quality of life," explained Lawrence F. Eichenfield, MD, chief of pediatric and adolescent dermatology at Rady Children's Hospital-San Diego, professor of dermatology and pediatrics and vice-chair of the department of dermatology at UC San Diego School of Medicine, and study investigator. "Adults and children who suffer with atopic dermatitis are in need of non-steroidal topical treatment options that are safe, well-tolerated, and suitable for long-term use. The strong results from this second pivotal Phase 3 trial, which are consistent with the findings from INTEGUMENT-1, further reinforce the safety and efficacy profile of roflumilast cream and its potential as a new treatment option for atopic dermatitis."

Roflumilast cream also demonstrated rapid and statistically significant improvements compared to vehicle on key secondary endpoints, including 42.0% of individuals treated with roflumilast cream 0.15% achieving a 75% improvement in Eczema Area and Severity Index (EASI-75) at Week 4 compared to 19.7% treated with vehicle (P<0.0001).

In an additional secondary endpoint, the study evaluated reduction in itch in individuals 12 years of age and older, with 30.2% of individuals treated with roflumilast cream achieving a 4-point reduction in Worst Itch Numeric Scale (WI-NRS) at Week 4 (vs. 12.4% for vehicle-treated subjects [p<0.01]).

AD is the most common type of eczema, affecting approximately 9.6 million children and 16.5 million adults in the United States. Topical therapies are an important treatment option for the majority of individuals who use pharmaceuticals to treat their disease.

"We are very pleased with these positive findings from INTEGUMENT-2, our second of two Phase 3 pivotal trials with roflumilast cream 0.15% in individuals with mild to moderate atopic dermatitis aged 6 years and older. Roflumilast cream delivered positive efficacy as early as Week 1 for symptomatic response in itch and Week 2 for IGA Success, as well as favorable safety and tolerability results," said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. "With these positive results, we plan to move forward with filing a supplemental new drug application (sNDA) with the United States Food & Drug Administration (FDA) for roflumilast cream 0.15% for the treatment of mild to moderate atopic dermatitis in adults and children 6 years of age and older in the second half of 2023."

"I am incredibly proud of the entire Arcutis team for their ability to complete enrollment and report positive results for four Phase 3 pivotal trials across three indications for topical roflumilast in 2022. All of this is on the heels of the FDA approval and successful launch of our first product in plaque psoriasis," said Frank Watanabe, president and CEO at Arcutis. "We are also deeply grateful for all of the investigators and individuals with atopic dermatitis, seborrheic dermatitis, and scalp and body psoriasis who volunteered to enroll in these trials."

Roflumilast cream 0.15% was well tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both active treatment and vehicle arms, with most TEAEs assessed as mild to moderate severity. Overall, incidence of adverse events were low, with no adverse event occurring in more than 3.5% of subjects in either arm. The most frequent adverse events in the roflumilast arm (≥1%) included headache, nausea, vomiting, diarrhea, and upper respiratory tract infection. Over 90% of patients who were randomized to roflumilast cream in the study completed the full four weeks, and there were few discontinuations due to adverse events (1.8% and 0.9% in the roflumilast cream and vehicle groups, respectively).

The Company will host a conference call to discuss the results of both INTEGUMENT-1 and INTEGUMENT-2 today at 8:30 a.m. ET. A live webcast of the call and the presentation material will be available on the "Events" section of the Company's investor website. An archived replay of the webcast will be available on the Arcutis investor website following the conference.

Summary of Topline Results from INTEGUMENT-1 and INTEGUMENT-2

Arcutis investigated roflumilast cream 0.15% in adults and children aged 6 and over with mild to moderate AD in two identical pivotal Phase 3 studies, INTEGUMENT-1 and INTEGUMENT-2. In November, the company reported positive topline findings from INTEGUMENT-1.

	INTEGUMENT-1 Week 4			INTEGUMENT-2 Week 4
	Roflumilast cream	Vehicle	P-value	Roflumilast cream	Vehicle	P-value
vIGA-AD	32.0%	15.2%	P<0.0001	28.9%	12.0%	P<0.0001
EASI-75	43.2%	22.0%	P<0.0001	42.0%	19.7%	P<0.0001
WI-NRS	33.6%	20.7%	P<0.01	30.2%	12.4%	P<0.01

About INTEGUMENT-2

The "INterventional Trial EvaluatinG roﬂUMilast cream for the treatmENt of aTopic dermatitis" 2 (INTEGUMENT-2) is a Phase 3, parallel group, double blind, vehicle-controlled trial in which roﬂumilast cream 0.15% or vehicle is applied once daily for four weeks to individuals 6 years of age and older with mild to moderate AD involving ≥3% body surface area. A total of 683 individuals were randomized in the study. The primary endpoint was IGA Success, deﬁned as vIGA-AD score of ‘clear' or ‘almost clear' plus a 2-grade improvement from baseline at Week 4. Multiple secondary endpoints were also evaluated, including itch as measured by WI-NRS as well as the proportion of subjects who attained at least a 75% improvement in EASI-75 at Week 4.

After completing INTEGUMENT-1 and INTEGUMENT-2, individuals were eligible to enroll in an open-label extension study (INTEGUMENT-OLE) evaluating treatment with once-daily roflumilast cream 0.15% for up to 12 months.

Arcutis is enrolling a third pivotal Phase 3 trial, the "INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis in PEDiatric patients" (INTEGUMENT-PED) to evaluate roflumilast cream 0.05% in children 2 to 5 years of age with mild to moderate AD. The Company plans to report topline data from this study in 2023.

About Atopic Dermatitis

AD is the most common type of eczema, affecting approximately 9.6 million children and 16.5 million adults in the U.S. AD is characterized by a defect in the skin barrier, which allows allergens and other irritants to enter the skin, leading to an immune reaction and inflammation. This reaction produces a red, itchy rash, most frequently occurring on the face, arms, and legs. The rash can cover significant areas of the body, in some cases half of the body or more. AD typically begins in early childhood and is chronic. It persists into adolescence and even adulthood in some individuals. The rash causes significant pruritus (itching), which can lead to skin damage caused by scratching or rubbing. Since a large percentage of AD patients are very young children, safety is a particularly important consideration in treatment selection.

About Roflumilast Cream

Roflumilast cream is a next generation topical PDE4 inhibitor. PDE4 – an established target in dermatology – is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators and has been implicated in a wide range of inflammatory diseases including psoriasis, eczema, and COPD. For AD, roflumilast cream is being evaluated at lower doses: 0.15% for adults and children 6 years of age and older, and 0.05% for children aged 2 to 5 years.

About Arcutis

Arcutis Biotherapeutics, Inc. (NASDAQ:ARQT) is an early commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio that harnesses our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis' dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions including scalp and body psoriasis, atopic dermatitis, seborrheic dermatitis, and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, and Twitter.

Forward-Looking Statements

Arcutis cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company's current beliefs and expectations. Such forward-looking statements include, among others, statements regarding the potential for roﬂumilast to be approved for the treatment of adults and children with AD, the potential to use roﬂumilast cream over a long period of time, or chronically, the potential to use roﬂumilast cream anywhere on the body, including the face and sensitive areas, timing for anticipated data of INTEGUMENT-PED, the potential sNDA ﬁling and the potential for roﬂumilast to advance the standard of care in AD and other inﬂammatory dermatologic conditions. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in our business, reimbursement and access to our products, the impact of competition and other important factors discussed in the "Risk Factors" section of our Form 10-K filed with U.S. Securities and Exchange Commission (SEC) on February 22, 2022, as amended, as well as any subsequent filings with the SEC. You should not place undue reliance on any forward-looking statements in this press release. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

Contacts:

Media

Amanda Sheldon, Head of Corporate Communications

asheldon@arcutis.com

Investors

Eric McIntyre, Head of Investor Relations

emcintyre@arcutis.com