PDE4 Inhibition and Theta-burst Stimulation Transcranial Magnetic Stimulation Motor Plasticity: a Randomized Placebo-controlled Single-blind Crossover Study

Repetitive transcranial magnetic stimulation (rTMS) uses a magnetic field to non-invasively induce electrical function within the brain. Stimulation allows brain cells to change the way that they adapt and communicate with each other, known as 'synaptic plasticity'. It is thought that alterations in these adaptive brain changes underlie the ability of rTMS to treat mental illnesses like depression.
The regulation of synaptic plasticity is complex, and involves multiple interacting factors and redundant systems to ensure that plasticity is carefully regulated. To date, studies attempting to alter impact synaptic plasticity have done so using pharmacological adjuncts that target extracellular contributions to plasticity. Here, we propose the first proof of principle study targeting intracellular regulation of plasticity by using a pharmacological adjunct targeting Phosphodiesterase 4 (PDE4), a key regulator a cyclic AMP gradients in brain cells.
We will pair TMS with electromyography (EMG) to measure activity dependent changes in the motor cortex following rTMS to test the ability of a PDE4 inhibition to enhance synaptic plasticity after rTMS.

Start Date01 Aug 2024

Sponsor / Collaborator

University of Calgary

NCT06440473 / RecruitingPhase 4

Visualization of Topical Zoryve vs. Vehicle Using Line Field Optical Coherence Tomography in Healthy Skin

The goal of this study is to visualize the deposition of topical 0.3% roflumilast (Zoryve) compared to vehicle using Line-Field Optical Coherence Tomography (LC-OCT) in vivo in healthy skin. We hypothesize that the application of topical 0.3% roflumilast (Zoryve) will result in distinct patterns of deposition within the epidermal and dermal layers compared to the vehicle. Specifically, we anticipate observing deeper penetration and more uniform distribution of roflumilast within the skin layers, indicative of enhanced efficacy, as visualized by LC-OCT imaging.

Start Date28 May 2024

Sponsor / Collaborator

Rao Dermatology

NCT05682859 / RecruitingPhase 4IIT

Treatment of Chronic Hand Eczema With Oral Roflumilast (HERO) - a Randomized Controlled Trial

This study is a multicentre, double-blinded, randomized, placebo-controlled, clinical trial with open-label extension.
The purpose and aim of this study is to investigate the efficacy and safety of roflumilast (PDE4-inhibitor) in adult patients with chronic hand eczema (CHE).
Patients will receive 16-week treatment with either roflumilast or placebo tablets. Hereafter, both groups continue in open-label treatment for 12 weeks where both groups will receive treatment with roflumilast.

Start Date25 Sep 2023

Sponsor / Collaborator

Novo Nordisk Foundation

100 Clinical Results associated with Roflumilast

100 Translational Medicine associated with Roflumilast

100 Patents (Medical) associated with Roflumilast

749

Literatures (Medical) associated with Roflumilast

01 Apr 2024·Journal of affective disorders

Roflumilast: Modulating neuroinflammation and improving motor function and depressive symptoms in multiple sclerosis

Article

Author: Zhang, Zhijun ; Chai, Jiaqing ; Wu, Yingying ; Zhang, Weiying ; Wang, Zhaowei ; Zhang, Yanxin

BACKGROUND:

Multiple sclerosis (MS) is an autoimmune disease causing central nervous system demyelination, often associated with depression. Current treatments for MS do not effectively address both physical disability and depression. Roflumilast, a phosphodiesterase-4 inhibitor with anti-inflammatory properties, has shown promise for autoimmune diseases.

METHODS:

We used an experimental autoimmune encephalomyelitis (EAE) rat model to study roflumilast's effects. Motor dysfunction and depression symptoms were assessed, and histopathological analysis evaluated its anti-inflammatory properties. Flow cytometry examined the drug's impact on brain microglia. TNF-α, IL-1β, and IL-6 levels in hippocampal tissue were assessed using ELISA kits.

RESULTS:

Roflumilast improved motor dysfunction and depression symptoms in EAE rats. Histopathological analysis revealed reduced inflammation, demyelination, and axonal loss in the spinal cord. Roflumilast suppressed microglial cell activation and conversion to pro-inflammatory M1-type cells. Flow cytometry showed roflumilast inhibited inflammatory marker expression in microglia and their activation in the hippocampus. IL-6 was identified as a roflumilast target for suppressing hippocampal inflammation.

LIMITATIONS:

This study used an animal model and did not assess long-term or potential side effects of roflumilast treatment.

CONCLUSIONS:

Roflumilast holds promise as a treatment for depression and motor impairment in MS. Its anti-inflammatory properties, reducing inflammation and inhibiting microglial activation, suggest its potential for MS therapy. However, further research is needed to evaluate long-term effects and safety in MS patients.

01 Feb 2024·International immunopharmacology

The IL-4/13-induced production of M2 chemokines by human lung macrophages is enhanced by adenosine and PGE2

Article

Author: Devillier, Philippe ; Glorion, Mathieu ; Naline, Emmanuel ; Brollo, Marion ; Grassin-Delyle, Stanislas ; Buenestado, Amparo ; Tiotiu, Angelica ; Descamps, Delphyne ; Salvator, Hélène ; Tenor, Hermann

BACKGROUND AND PURPOSE:

Lung macrophages (LMs) are critically involved in respiratory diseases. The primary objective of the present study was to determine whether or not an adenosine analog (NECA) and prostaglandin E₂ (PGE₂) affected the interleukin (IL)-4- and IL-13-induced release of M2a chemokines (CCL13, CCL17, CCL18, and CCL22) by human LMs.

EXPERIMENTAL APPROACH:

Primary macrophages isolated from resected human lungs were incubated with NECA, PGE₂, roflumilast, or vehicle and stimulated with IL-4 or IL-13 for 24 h. The levels of chemokines and PGE₂ in the culture supernatants were measured using ELISAs and enzyme immunoassays.

KEY RESULTS:

Exposure to IL-4 (10 ng/mL) and IL-13 (50 ng/mL) was associated with greater M2a chemokine production but not PGE₂ production. PGE₂ (10 ng/mL) and NECA (10^-6 M) induced the production of M2a chemokines to a lesser extent but significantly enhanced the IL-4/IL-13-induced production of these chemokines. At either a clinically relevant concentration (10^-9 M) or at a concentration (10^-7 M) that fully inhibited phosphodiesterase 4 (PDE4) activity, roflumilast did not increase the production of M2a chemokines and did not modulate their IL-13-induced production, regardless of the presence or absence of PGE₂.

CONCLUSIONS:

NECA and PGE₂ enhanced the IL-4/IL-13-induced production of M2a chemokines. The inhibition of PDE4 by roflumilast did not alter the production of these chemokines. These results contrast totally with the previously reported inhibitory effects of NECA, PGE₂, and PDE4 inhibitors on the lipopolysaccharide-induced release of tumor necrosis factor alpha and M1 chemokines in human LMs.

Calcified tissue international

Effect of Roflumilast, a Selective PDE4 Inhibitor, on Bone Phenotypes in ADO2 Mice

Article

Author: Acton, Dena ; Hong, Jung Min ; Parker, Reginald S ; Econs, Michael J ; Gerard-O'Riley, Rita L ; Hardman, Sara L ; Bruzzaniti, Angela ; Alam, Imranul

Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption that usually results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene. We previously created mouse models of ADO2 (p.G213R) with one of the most common mutations (G215R) as found in humans and demonstrated that this mutation in mice phenocopies the human disease of ADO2. Previous studies have shown that roflumilast (RF), a selective phosphodiesterase 4 (PDE4) inhibitor that regulates the cAMP pathway, can increase osteoclast activity. We also observed that RF increased bone resorption in both wild-type and ADO2 heterozygous osteoclasts in vitro, suggesting it might rescue bone phenotypes in ADO2 mice. To test this hypothesis, we administered RF-treated diets (0, 20 and 100 mg/kg) to 8-week-old ADO2 mice for 6 months. We evaluated bone mineral density and bone micro-architecture using longitudinal in-vivo DXA and micro-CT at baseline, and 6-, 12-, 18-, and 24-week post-baseline time points. Additionally, we analyzed serum bone biomarkers (CTX, TRAP, and P1NP) at baseline, 12-, and 24-week post-baseline. Our findings revealed that RF treatment did not improve aBMD (whole body, femur, and spine) and trabecular BV/TV (distal femur) in ADO2 mice compared to the control group treated with a normal diet. Furthermore, we did not observe any significant changes in serum levels of bone biomarkers due to RF treatment in these mice. Overall, our results indicate that RF does not rescue the osteopetrotic bone phenotypes in ADO2 heterozygous mice.

118

News (Medical) associated with Roflumilast

01 Jul 2024

·www.biospace.com

FDA Action Alert: Arcutis, Orexo, Phantom and More

Pictured: A scientist with pill bottles in front of FDA headquarters/Taylor Tieden for BioSpace Coming off of a busy month, July is looking relatively quiet for the FDA, with only five big target action dates and one pivotal advisory committee meeting. Read below for more. Arcutis Proposes New Atopic Dermatitis Cream for Patients as Young as Six By July 7, the FDA is expected to release its verdict on Arcutis Biotherapeutics’ supplemental New Drug Application (sNDA), seeking approval for a 0.15% formulation of roflumilast cream for the treatment of atopic dermatitis in patients as young as 6 years. Roflumilast is a topical inhibitor of the phosphodiesterase 4 (PDE4) enzyme, which plays a role in increasing the production of pro-inflammatory mediators while dampening the body’s anti-inflammatory mechanisms. A 0.3% formulation of roflumilast is approved under the brand name Zoryve for the treatment of psoriasis in patients 6 years and older. The FDA in December 2023 expanded roflumilast’s indication, allowing its use for seborrheic dermatitis in patients aged 9 and above. Arcutis is backing roflumilast’s atopic dermatitis application with data from three Phase III programs, including INTEGUMENT-1 and INTEGUMENT-2, two identical parallel-group, double-blinded and vehicle-controlled studies. The 0.15% roflumilast cream aced these two studies, hitting four-week success rates of 32.0% and 28.9%, respectively. In January 2024, Arcutis released additional pooled analysis from these two trials, demonstrating that 91.5% of patients treated with 0.15% roflumilast saw an improvement in the Eczema Area and Severity Index, measured at 4 weeks. Roflumilast’s data package also included a Phase II dose-ranging study and a Phase I pharmacokinetic trial. Orexo’s Opioid Overdose Drug Awaits FDA Verdict Orexo AB is proposing its high-dose naloxone drug candidate OX124 as a nasal rescue treatment for opioid overdose. The FDA’s deadline for a decision is July 15. Originally approved under the brand name Narcan, naloxone is a well-known treatment for opioid overdose. Currently available as an injectable and as a nasal spray, it works by competing with opioids for the same receptor sites, thereby undoing and dampening the drugs’ effects. Naloxone is effective at reversing the respiratory depression, hypotension and sedation often seen in patients who overdose on opioids. Orexo’s investigational formulation of naloxone makes use of its “world-class drug delivery platform,” dubbed amorphOX, according to the company’s news release accompanying the acceptance of its NDA. Through amorphOX, Orexo delivers a powder formulation of naloxone that is rapidly absorbed, highly bioavailable and highly stable. AmorphOX also makes naloxone more convenient and easier to use for patients, according to the company, making the product more robust to temperature changes. For instance, its efficacy is unaffected even if stored at freezing temperatures. If approved, Orexo expects to kick off commercial activities in the second half of this year, with a broader retail launch scheduled in early 2025, CEO Nikolaj Sørensen said in a statement. Phathom Pushes Voquezna into Heartburn in GERD The FDA is reviewing Phathom Pharmaceuticals’ application to use its oral drug Voquezna (vonoprazan) for the treatment of heartburn associated with non-erosive gastroesophageal reflux disease (GERD). Its decision is due on July 19. Afflicting around 38 million adults in the U.S., non-erosive GERD is the most common type of GERD and is characterized by reflux symptoms without mucosal erosions in the esophagus. Among its most common signs is episodic heartburn, which typically occurs at night. Patients with non-erosive GERD also suffer from regurgitation and chest pain and often have trouble swallowing. Voquezna, a potassium-competitive acid blocker, works by suppressing acid secretion and acts with preference on parietal cells found in the stomach. This mechanism of action helped the drug win its first FDA approval in November 2023, allowing its use for the treatment of erosive GERD and the relief of heartburn in erosive GERD. The NDA, which Phathom filed in September 2023, is backed by a randomized, placebo-controlled and double-blinded trial with 772 enrolled patients. Results showed that both the 10-mg and 20-mg doses of Voquezna aced the trial's primary endpoint, resulting in a 45% and 44% mean percentage of heartburn-free days over the 4-week treatment period, respectively, whereas this figure was only 28% in placebo comparators. During the study’s 20-week extension phase, the mean percentage of heartburn-free days in the 10-mg and 20-mg treatment groups increased to 62% and 63%, respectively. Alpha Cognition Targets Second Oral Alzheimer’s Drug of the Past Decade By July 27, the FDA is set to release its decision on Alpha Cognition’s NDA for ALPHA-1062, a next-generation acetylcholinesterase inhibitor being proposed for the treatment of mild-to-moderate Alzheimer’s disease. Formulated as a delayed-release oral tablet, ALPHA-1062 is the prodrug of an already-approved acetylcholinesterase inhibitor, galantamine, according to Alpha Cognition. The candidate works through a similar pathway, boosting the activity of acetylcholine on nicotinic receptors and the cholinergic neurotransmission in the central nervous system, in turn inducing cognitive improvements. Compared with galantamine, however, ALPHA-1062 promises a cleaner safety profile. It carries additional benzoyl ester moieties, which allow it to bypass acetylcholine receptors in the gastrointestinal nervous system, thereby avoiding the unwanted stimulation of local neurons and reducing side effects, according to Alpha Cognition’s website. ALPHA-1062’s NDA, which the FDA accepted in December 2023, is supported by studies establishing the bioequivalence of the drug candidate to galantamine. If approved, ALPHA-1062 would be the second oral Alzheimer’s therapy in a decade, according to a February 2024 release from Alpha Cognition. Xspray Tries Again for CML Therapy Dasynoc In February 2024, the FDA accepted Xspray Pharma’s NDA resubmission for Dasynoc (dasatinib), being proposed for the treatment of chronic myeloid leukemia. The regulator’s verdict is due on July 31. According to Xspray’s news release alongside the NDA’s acceptance, Dasynoc is an “optimized version” of Bristol Myers Squibb’s dasatinib, which the pharma sells under the brand name Sprycel. For instance, Dasynoc is unaffected by stomach pH and can be used together with omeprazole, as per Xspray’s website. Dasynoc also has a more consistent uptake pro can be given at lower doses than Sprycel. In July 2023, the FDA rejected Xspray’s initial bid to win approval for Dasynoc. At the time, the regulator accepted the proposed brand name and did not identify deficiencies with the application’s stability and clinical data. Instead, the FDA requested additional information regarding Dasynoc’s dosing in order to avoid confusion among doctors and patients. The regulator also asked for more information regarding a third-party manufacturer. In a February 2024 news release, CEO Per Andersson said that despite the initial rejection, Xspray remains “on track” to launch Dasynoc on September 1, if approved. FDA’s ODAC Convenes to Discuss AstraZeneca’s Imfinzi Regimen in NSCLC On July 25, the FDA’s Oncologic Drugs Advisory Committee will meet to discuss AstraZeneca’s supplemental Biologics License Application for its antibody therapy Imfinzi (durvalumab) for the treatment of resectable non-small cell lung cancer (NSCLC). The panel of external experts will evaluate AstraZeneca’s application for neoadjuvant treatment with Imfinzi and chemotherapy, followed by Imfinzi monotherapy after surgery. The advisory committee will also evaluate whether the pharma should be required to justify Imfinzi treatment before and after surgery. Imfinzi is a monoclonal antibody designed to target and block the PD-L1 protein, in turn inhibiting its downstream signaling cascade. This mechanism hampers cancer cells’ ability to weaken and evade the immune system, while also boosting the body’s innate anti-cancer activity. The FDA first approved Imfinzi in May 2017 for the treatment of advanced bladder cancer. The treatment has since been indicated for several other cancers, including unresectable stage III NSCLC, biliary tract cancer, pancreatic cancer and advanced or recurrent endometrial cancer. In April 2023, AstraZeneca published data from the Phase III AEGEAN study showing that neoadjuvant Imfinzi with chemotherapy, followed by maintenance Imfinzi monotherapy, significantly improved event-free survival in patients with resectable early-stage NSCLC versus chemotherapy alone. The Imfinzi-based regimen also resulted in a significantly higher pathologic complete response. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Phase 3Clinical ResultDrug ApprovalPhase 2NDA

10 Jun 2024

·www.globenewswire.com

Arcutis Announces New Long-Term Data of Roflumilast Cream 0.15% for the Treatment of Mild to Moderate Atopic Dermatitis (AD) in Adults and Children Down to Age Six Presented at Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference

Investigational roflumilast cream 0.15% showed continued improvements in the signs and symptoms of AD, including itch, through 56 weeks of treatment66.2% of participants treated with once-daily roflumilast cream 0.15% in both the 4-week parent study and the 52-week open label extension achieved a 75% improvement in Eczema Area and Severity Index (EASI-75) at Week 56For participants who achieved disease clearance and switched to proactive twice weekly application of roflumilast cream, the median duration of disease control was 281 daysOnce-daily, roflumilast cream 0.15% was well tolerated, with no new safety signals observed for up to 56 weeks of treatment CHICAGO and WESTLAKE VILLAGE, Calif., June 10, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced new results from the INTEGUMENT-OLE long-term open-label study of investigational once-daily roflumilast cream 0.15% in adults and children ages 6 years and older with AD presented at the Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference. In the study, roflumilast cream was well-tolerated, with no new safety signals observed over 56 weeks of treatment. Efficacy was not only maintained but improved over time, with 56.6% of participants who continued use of roflumilast cream from the initial trial and 53.8% of participants who switched to roflumilast cream 0.15% from vehicle after the initial trial achieving validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) success, defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, at Week 56. Starting at Week 4 of INTEGUMENT-OLE, participants who achieved a vIGA-AD score of clear (0), switched to proactive twice-weekly application (130 participants; 19.8% of study population). For these participants, after their first switch to twice-weekly application, the median duration of disease control (maintaining vIGA-AD of 0 or 1 with adequate control of signs and symptoms on the twice-weekly schedule application) was 281 days (95% CI: 147, not evaluable). In addition, 57.7% of these participants maintained disease control on the twice weekly schedule through their final study day. “AD is a chronic, burdensome skin condition that requires clinicians and patients to seek a treatment option that can be safely and effectively used long-term for an adult or child,” said Melinda Gooderham, MSc, MD, FRCPC, medical director, SKiN Centre for Dermatology, investigator with Probity Medical Research, and study presenter. “Importantly, investigational roflumilast cream 0.15% showed continued improvement through the course of the study, demonstrating that once approved, roflumilast cream may be an effective long-term, steroid-free treatment option that can be used for proactive flare-free disease control. These results also reinforce the durable efficacy and tolerability of roflumilast cream in AD, which could translate to improved treatment adherence.” “Adults and children with AD deserve treatment standards that focus on maintaining long-term disease control, rather than reactively managing flares. This novel pivotal study design evaluated proactive twice-weekly application with a targeted topical treatment, and demonstrates that after achieving disease clearance, patients can maintain disease control for at least 281 days,” said Emma Guttman-Yassky, MD, PhD, Waldman Professor of Dermatology and Immunology, Icahn School of Medicine at Mount Sinai, chair of the Kimberly and Eric J. Waldman Department of Dermatology, Mount Sinai Health System, and director of the Laboratory for Inflammatory Skin Diseases at Mount Sinai. “These results provide support for shifting the paradigm from reactively chasing flares to long-term flare-free disease management.” Dr. Guttman-Yassky is a paid consultant with Arcutis Biotherapeutics. Additional results presented include: 66.2% and 64.6% of participants who rolled over from the roflumilast cream arm in INTEGUMENT-1 or -2 or switched to once-daily roflumilast cream 0.15% from the vehicle arm demonstrated a 75% improvement from baseline in EASI-75 after 56 weeks, respectively.56.9% and 50.0% of participants who rolled over from or switched to once-daily roflumilast cream 0.15% treatment achieved a significant reduction (≥4-point) in itch based on daily Worst Itch Numeric Rating Scale (WI-NRS) (among patients aged ≥12 years with baseline WI-NRS ≥4) at Week 56, respectively. These long-term study results provide further support for the safety and tolerability profile of roflumilast cream already seen in the pivotal INTEGUMENT-1 and INTEGUMENT-2 clinical trials, with no new safety signals observed up to 56 weeks. Overall incidence of adverse events was low, with most being mild to moderate in severity. The most frequently reported adverse events (≥2%) included: COVID-19, upper respiratory tract infection, nasopharyngitis, and headache. Overall, only 3.0% of trial participants discontinued the study due to adverse events. “Investigational roflumilast cream 0.15% is designed to provide clinicians and individuals with AD with a long-term treatment option that is formulated free of known ingredients or allergens that may disrupt and compromise skin barrier integrity,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “Based on these positive results, individuals can expect long-term efficacy and improvement in the signs and symptoms of AD, including itch, from roflumilast cream. If approved, we believe that roflumilast cream offers patients with AD an important steroid-free topical option that can provide lasting symptom relief which is maintained over time.” Roflumilast cream is uniquely formulated as a non-greasy emollient cream that absorbs quickly and does not disrupt the skin barrier. In addition, roflumilast cream does not include sensitizing excipients or irritants, such as propylene glycol, polyethylene glycol, isopropyl alcohol, ethanol, or fragrances. About INTEGUMENT-OLEThe “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis Open Label Extension” (INTEGUMENT-OLE) was a Phase 3, multicenter, open-label extension study of the long-term safety of roflumilast cream 0.15% in adults and children ages 6 years and older with AD and roflumilast cream 0.05% in children ages 2 to 5 years. Individuals completing the INTEGUMENT-1 or INTEGUMENT-2 Phase 3 trials were eligible to enroll (n=658) for either 24 or 52 weeks. Reported here are data from adults and children down to age 6. The study evaluated monotherapy with roflumilast cream with no rescue treatment permitted. Beginning at Week 4 of INTEGUMENT-OLE, any participant who achieved vIGA-AD of ‘0-Clear’ switched to twice-weekly proactive treatment. Participants were able to continue twice-weekly proactive dosing, as long as vIGA-AD remained either ‘0-Clear’ or ‘1-Almost Clear’. Participants resumed once-daily dosing if vIGA-AD reached ≥2-Mild and could also resume once-daily dosing if signs/symptoms of AD were not adequately controlled with proactive therapy despite remaining at vIGA-AD of ‘1-Almost Clear’. The primary objective of the study was to assess the long-term safety of roflumilast cream after either 24 or 52 weeks of treatment. Secondary endpoints include vIGA-AD score of 0 or 1 at each assessment, vIGA-AD success, WI-NRS score over time, and EASI score over time. The assessment of IGA Success and EASI-75 response, as reported here, references baseline of INTEGUMENT-1 and -2. About Atopic DermatitisThe most common type of eczema, AD affects approximately 9.6 million children and 16.5 million adults in the United States. AD is a chronic, relapsing inflammatory skin disease that is genetically pre-disposed and presents across the lifespan. The disease appears as a red, intensely itchy rash that can occur anywhere on the body and may present differently in children and adults. AD presentation can rapidly fluctuate and vary based on geographic location and environment. About Roflumilast CreamRoflumilast cream is a next generation topical phosphodiesterase-4 (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. Roflumilast cream 0.3% (ZORYVE®) is approved by the Food and Drug Administration (FDA) for the topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. Investigational roflumilast cream was evaluated at lower doses for AD: 0.15% for adults and children 6 years of age and older and 0.05% for children aged 2 to 5 years. Roflumilast cream 0.15% is under review at the FDA for the treatment of adults and children 6 years of age and older with a Prescription Drug User Fee Act (PDUFA) target action date of July 07, 2024. Arcutis intends to submit a supplemental new drug application (sNDA) for roflumilast cream 0.05% in ages 2 to 5 following the potential approval of roflumilast cream 0.15%. About ZORYVE CreamZORYVE (roflumilast) cream is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. IMPORTANT SAFETY INFORMATIONZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). The most common adverse reactions (≥1%) include diarrhea (3.1%), headache (2.4%), insomnia (1.4%), nausea (1.2%), application site pain (1.0%), upper respiratory tract infection (1.0%), and urinary tract infection (1.0%). Please see full Prescribing Information. About ArcutisArcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a 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 including two FDA approved products that harness 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, AD, and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, Instagram and X. Forward-Looking StatementsArcutis 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, but are not limited to, statements regarding the potential of roflumilast cream to simplify disease management for care of AD; the potential of real-world use results of roflumilast cream, as well as the potential approval of roflumilast cream for AD. 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 27, 2024, 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:MediaAmanda Sheldon, Head of Corporate Communicationsasheldon@arcutis.com InvestorsLatha Vairavan, Vice President, Finance and Investor Relationslvairavan@arcutis.com

Clinical ResultPhase 3Drug Approval

05 Jun 2024

·www.globenewswire.com

Arcutis Announces Multiple Abstracts, Including Oral Presentation, Accepted at the Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference

New long-term safety and efficacy data of investigational roflumilast cream 0.15% in mild to moderate atopic dermatitis will be presented in an oral sessionPreclinical data on ARQ-234, CD200R agonist, for the treatment of atopic dermatitisAdditional presentation of the consistent tolerability profile of topical roflumilast in psoriasis, seborrheic dermatitis, and atopic dermatitis WESTLAKE VILLAGE, Calif., June 05, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a commercial-stage company focused on developing meaningful innovations in immuno-dermatology, today announced that five abstracts will be presented at the Revolutionizing Alopecia Areata, Vitiligo, and Eczema Conference, which will take place in Chicago, IL from June 8-10, 2024. Among these presentations will be new long-term safety and efficacy data for roflumilast cream 0.15% in patients ≥6 years of age with mild to moderate atopic dermatitis, and an encore of preclinical data on ARQ-234, a CD200 receptor agonist the Company is investigating for atopic dermatitis. In addition, the Company will present investigator- and patient-rated local tolerability data evaluating topical roflumilast in patients with psoriasis, seborrheic dermatitis, and atopic dermatitis. “We are committed to providing therapeutic innovation and advancing the standard of care for those living with chronic, immune-mediated skin diseases and look forward to sharing these exciting scientific findings including data for roflumilast cream for adults and children with atopic dermatitis from our INTEGUMENT program,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer, Arcutis. “We also look forward to sharing preclinical data from our pipeline for ARQ-234, a biologic we are developing for the treatment of atopic dermatitis.” Presentation details follow: Oral Poster PresentationLong-term Safety and Efficacy of Roflumilast Cream 0.15% in Adults and Children Aged ≥6 Years With Mild to Moderate Atopic Dermatitis:A 52-week, Phase 3, Open-Label Safety TrialPresenting Author: Melinda Gooderham, MD, FRCPCTime: June 10, 1:30 pm CTAbstract number: 634 The following posters will be electronically available for the entirety of the conference and online beginning Saturday, June 8, 2024 at 6:00 pm CT. Pooled Efficacy, Patient-Reported Outcomes, and Safety of Roflumilast Cream 0.15% From the INTEGUMENT-1 and INTEGUMENT-2 Phase 3 Clinical Trials of Adults and Children With Atopic DermatitisSimpson, E et al.ePoster 641 Efficacy and Safety of Once-Daily Roflumilast Cream 0.05% in Pediatric Patients 2 to 5 Years of Age with Mild to Moderate Atopic Dermatitis (INTEGUMENT-PED): A Phase 3 Randomized Controlled TrialEichenfield, L et al.ePoster 639 ARQ-234: a high affinity CD200-Fc fusion protein for the treatment of atopic dermatitisSheridan, J et al.ePoster 637 Investigator- and patient-rated local tolerability in phase 3 trials of topical roflumilast in patients with psoriasis, seborrheic dermatitis, and atopic dermatitisBunick, C et al.ePoster 640 About ArcutisArcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a 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 including two FDA approved products that harness 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, and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, Instagram and X. INDICATIONSZORYVE cream is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. ZORYVE foam, 0.3%, is indicated for treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. IMPORTANT SAFETY INFORMATION ZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). Flammability: The propellants in ZORYVE foam are flammable. Avoid fire, flame, and smoking during and immediately following application. The most common adverse reactions (≥1%) for ZORYVE cream include diarrhea (3.1%), headache (2.4%), insomnia (1.4%), nausea (1.2%), application site pain (1.0%), upper respiratory tract infection (1.0%), and urinary tract infection (1.0%). The most common adverse reactions (≥1%) for ZORYVE foam include nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%). Please see full Prescribing Information for ZORYVE foam and full Prescribing Information for ZORYVE cream. Forward-Looking StatementsArcutis 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, but are not limited to, statements regarding the potential for topical roflumilast to advance the standard of care in inflammatory dermatological 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 27, 2024, 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:MediaAmanda Sheldon, Head of Corporate Communicationsasheldon@arcutis.com InvestorsLatha Vairavan, Vice President, Finance and Investor Relationslvairavan@arcutis.com

Phase 3

100 Deals associated with Roflumilast

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KEGG	Wiki	ATC	Drug Bank
D05744	Roflumilast	R03DX07	DB01656

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Dermatitis, Seborrheic	US	Arcutis Biotherapeutics, Inc.	15 Dec 2023
Plaque psoriasis	CA	Arcutis Biotherapeutics, Inc.	20 Dec 2019
Pulmonary Disease, Chronic Obstructive	EU	AstraZeneca AB	05 Jul 2010
Pulmonary Disease, Chronic Obstructive	IS	AstraZeneca AB	05 Jul 2010
Pulmonary Disease, Chronic Obstructive	LI	AstraZeneca AB	05 Jul 2010
Pulmonary Disease, Chronic Obstructive	NO	AstraZeneca AB	05 Jul 2010

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Dermatitis, Atopic	NDA/BLA	US	Arcutis Biotherapeutics, Inc.	29 Nov 2023
Scalp Dermatoses	Phase 3	US	Arcutis Biotherapeutics, Inc.	24 Aug 2021
Scalp Dermatoses	Phase 3	CA	Arcutis Biotherapeutics, Inc.	24 Aug 2021
Asthma	Phase 3	US	AstraZeneca PLC	01 Nov 2003
Asthma	Phase 3	AR	AstraZeneca PLC	01 Nov 2003
Asthma	Phase 3	CO	AstraZeneca PLC	01 Nov 2003
Asthma	Phase 3	MX	AstraZeneca PLC	01 Nov 2003
Asthma	Phase 3	PE	AstraZeneca PLC	01 Nov 2003
Asthma chronic	Phase 3	US	AstraZeneca PLC	01 Apr 2003
Asthma chronic	Phase 3	AT	AstraZeneca PLC	01 Apr 2003

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04445987 (CTgov)	Phase 2	Dermatitis, Seborrheic	408	ARQ-154-203 Roflumilast Foam (Cohort 1 Group 1: ARQ-154-203 Roflumilast Foam 0.3% Without Treatment Gap)	aqwabvtcwa(xcpzarrjhi) = qcavikphyn qhyrirytrk (rhfdduhnsi, mwpadihfyj - zxfmwppvha) View more	-	11 Jun 2024
				ARQ-154-203 Roflumilast Foam (Cohort 2 Groups 3 and 4: ARQ-154-203 Roflumilast Foam 0.3% With Treatment Gap)	aqwabvtcwa(xcpzarrjhi) = rkmllamwuv qhyrirytrk (rhfdduhnsi, sdoxvodphw - wcirwylpoa)
NCT04804605 (INTEGUMENT-OLE, GlobeNewswire) Manual	Phase 3	Dermatitis, Atopic	658	Roflumilast cream 0.15% (INTEGUMENT-1)	azjjezqtim(gfpcklrleb) = lvahhdwmqd odgeygpjpp (xpkjxugvpf ) View more	Positive	10 Jun 2024
				Roflumilast cream 0.15% (INTEGUMENT-2)	azjjezqtim(gfpcklrleb) = fbhvbystqm odgeygpjpp (xpkjxugvpf ) View more
Literature Manual	Not Applicable	Dermatitis, Seborrheic	-	roflumilast foam formulation	-	Positive	13 May 2024
NCT04973228 (CTgov)	Phase 3	Dermatitis, Seborrheic	457	Roflumilast Foam (Roflumilast Foam 0.3%)	rbreglujwu(uvfumcuhdx) = mvkdbrbvni mosjfnfues (prkumatzul, lzyzfmdreg - lvwxefrsor) View more	-	12 Mar 2024
				Vehicle Foam (Vehicle Foam)	rbreglujwu(uvfumcuhdx) = ttykpynppf mosjfnfues (prkumatzul, ijqqysdwsb - ooloeundha) View more
NCT04845620 (INTEGUMENT-PED, GlobeNewswire) Manual	Phase 3	Dermatitis, Atopic	652	Roflumilast cream 0.05%	ihrvsmkfbb(gkezxuitat) = uctwnbccur urhwzeaxyk (cumqolbdzu ) View more	Positive	11 Mar 2024
				Vehicle	ihrvsmkfbb(gkezxuitat) = akwobfqjry urhwzeaxyk (cumqolbdzu ) View more
NCT04773587 \| NCT04773600 (INTEGUMENT-2 \| INTEGUMENT-II, GlobeNewswire) Manual	Phase 3	Dermatitis, Atopic	-	Roflumilast	adyfckauhd(dhbhkdhzgw) = myflagbzuz cexhnmzxvm (syvfwttzaz ) View more	Positive	14 Jan 2024
				Vehicle cream	adyfckauhd(dhbhkdhzgw) = qijlkpyuyp cexhnmzxvm (syvfwttzaz ) View more
NCT04973228 (STRATUM, GlobeNewswire) Manual	Phase 3	Dermatitis, Seborrheic	189	Roflumilast	tymwtwcmah(zsnrvuxeqo) = Treatment with ZORYVE foam significantly increased the odds of achieving a meaningful improvement in quality of life at Weeks 2, 4, and 8, compared to vehicle as measured by the Dermatology Life Quality Index (DLQI) (odds ratio (OR) 6:97; 95% confidence interval (CI) 3.97, 12.24; p<0.001). 72.5% of individuals achieved a minimally important differenceii in DLQI score as early as 2 weeks, increasing to 86.6% at the end of the study, Week 8 (compared to 28.1% p=0.001 and 53.6% p=0.001 for vehicle, respectively). qkffgepuov (vhneyhwdny )	Positive	14 Jan 2024
				Vehicle
NCT04091646 \| NCT04973228 (Trial 203, FDA) Manual	Phase 2/3	Dermatitis, Seborrheic	683	ZORYVE (STRATUM)	plhhxuxxxx(xauykgtkhc) = fwheovkisd jcdqohmput (sjaqqhbtbd ) View more	Positive	15 Dec 2023
				Vehicle (STRATUM)	plhhxuxxxx(xauykgtkhc) = yeytlgpnhn jcdqohmput (sjaqqhbtbd ) View more
NCT04655313 (ARQ-151-215, CTgov)	Phase 2	Plaque psoriasis	20	ARQ-151 cream 0.3%	iadkqnhtuz(zhtcvyzxyk) = icyxotweyj fvgiomoobf (jmdyioiqdq, iufgjwlyym - atcbhzlgxj) View more	-	15 Dec 2023
NCT04211363 \| NCT04211389 (DERMIS-2, Corporate Publications) Manual	Phase 3	Plaque psoriasis	-	ZORYVE® (roflumilast) cream 0.3%	qkiomadrgd(pmdshjrsoo) = fkzmmzulwy rsqfglmiod (qxacmddxoa ) View more	Positive	20 Oct 2023
				Vehicle	qkiomadrgd(pmdshjrsoo) = bcstqixrrd rsqfglmiod (qxacmddxoa ) View more

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