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.

开始日期2024-08-01

申办/合作机构

University of Calgary

NCT06440473 / Recruiting临床4期

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.

开始日期2024-05-28

申办/合作机构

Rao Dermatology

NCT05682859 / Recruiting临床4期IIT

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.

开始日期2023-09-25

申办/合作机构

Bispebjerg Hospital

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100 项与罗氟司特相关的转化医学

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100 项与罗氟司特相关的专利（医药）

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752

项与罗氟司特相关的文献（医药）

2024-04-01·Journal of affective disorders

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

Article

作者: 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.

2024-02-01·International immunopharmacology

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

Article

作者: Glorion, Mathieu ; Devillier, Philippe ; 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

作者: 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.

215

项与罗氟司特相关的新闻（医药）

2024-09-19

·GlobeNewswire-Health Care

Arcutis Announces Publication of ZORYVE® (roflumilast) Cream 0.15% Pivotal Results from Phase 3 INTEGUMENT-1 and -2 Trials in Mild to Moderate Atopic Dermatitis in Journal of American Medical Association Dermatology

ZORYVE® (roflumilast) cream 0.15% improved atopic dermatitis (AD) across multiple efficacy endpoints while demonstrating favorable safety and tolerabilityAcross both studies, approximately 31% of children and adults treated with ZORYVE cream achieved the primary efficacy endpoint of Investigator Global Assessment (IGA) Success at Week 4 compared to 14% for vehicle, with significant improvement as early as Week 1ZORYVE cream 0.15% rapidly and significantly reduced itch, the most bothersome symptom of ADOnce-daily, ZORYVE cream 0.15% is approved to treat mild to moderate AD in adults and children down to age 6 WESTLAKE VILLAGE, Calif., Sept. 19, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (Nasdaq: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced that the Journal of American Medical Association Dermatology (JAMA Dermatology) published the positive results from two pivotal Phase 3 studies (INTEGUMENT-1 and INTEGUMENT-2) evaluating the efficacy and safety of ZORYVE® (roflumilast) cream 0.15% as a once-daily, steroid-free treatment for mild to moderate AD. ZORYVE cream, 0.15%, was approved in July 2024 by the U.S. Food and Drug Administration (FDA) for the topical treatment of mild to moderate AD in adult and pediatric patients 6 years of age and older and is available in pharmacies nationwide. The article reported that treatment with ZORYVE cream resulted in significant improvements across multiple efficacy endpoints, including achieving a statistically significant improvement in the primary efficacy endpoint of IGA Success, as well as statistically significant improvements in key secondary endpoints, including itch and a reduction in Eczema Area and Severity Index score. “AD is a chronic and burdensome disease that often leaves patients and caregivers searching for relief from intractable itch, the most reported symptom which leads to reduced quality of life and sleep disturbances,” said Eric Simpson, MD, MCR, FAAD, Professor of Dermatology at Oregon Health & Science University in Portland and lead author on the publication. “These compelling results reinforce the strong efficacy and safety profile of ZORYVE and its ability to provide rapid and significant itch relief. Skin barrier is another key consideration for the treatment of AD, and these data further demonstrate that ZORYVE may be relied upon to deliver results without concerns for further disrupting the skin barrier.” INTEGUMENT-1 and INTEGUMENT-2 (The INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis) were two identical Phase 3, parallel group, double-blind, vehicle-controlled trials evaluating the safety and efficacy of ZORYVE cream 0.15% or vehicle applied once-daily for four weeks to 1,337 adults and children 6 years of age and older with mild to moderate AD. As previously reported, both INTEGUMENT-1 and -2 studies met their primary endpoint of 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 (INTEGUMENT-1: 32.0% ZORYVE cream vs. 15.2% vehicle, P<0.0001; INTEGUMENT-2: 28.9% ZORYVE cream vs. 12.0% vehicle, P<0.0001). Other key findings included: Rapid improvement in itch was observed in individuals treated with ZORYVE cream within 24 hours of the first application, as measured by the change from baseline in daily Worst Itch-Numeric Rating Scale (WI-NRS) scores and compared with vehicle (nominal P<0.05).Over 30% of individuals treated with ZORYVE cream in each study achieved WI-NRS Success at Week 4 compared to vehicle (INTEGUMENT-1: 33.6% vs 20.7% P<0.01; INTEGUMENT-2: 30.2% vs 12.4% P<0.01), with significant improvements seen as early as Week 1. WI-NRS Success is defined as achievement of at least a 4-point reduction on the WI-NRS 0-10 scale (in individuals ages 12 and older who had a baseline WI-NRS score of ≥ 4).More than 40% of children and adults treated with ZORYVE cream achieved a 75% reduction in Eczema Area and Severity Index (EASI-75) score at Week 4 compared to vehicle (INTEGUMENT-1: 43.2% vs. 22.0%, P<0.0001; INTEGUMENT-2: 42.0% vs. 19.7%, P<0.0001). Significant improvements based on EASI-75 were observed with ZORYVE cream compared to vehicle as early as Week 1 in both studies (nominal P=0.0006; nominal P=0.0329).ZORYVE cream 0.15% was safe and well tolerated. The incidence of Treatment Emergent Adverse Events (TEAEs) was low in both active treatment and vehicle arms.At each time point, investigators noted 95% of ZORYVE-treated patients had no signs of irritation at the application site. More than 90% of ZORYVE-treated patients self-reported no sensation or mild sensation at the application site. “We are thrilled that JAMA Dermatology, a premier medical journal, has published the positive results of our two pivotal Phase 3 trials. These data highlight the robust efficacy of ZORYVE to rapidly relieve AD, including the most troublesome symptom of itch,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “As an effective, safe, and well-tolerated once-daily cream, ZORYVE offers those living with AD and their caregivers a new treatment option for use anywhere on the body—and for any duration.” About Atopic Dermatitis AD is the most common type of eczema, affecting 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 ZORYVE®ZORYVE is a steroid-free topical phosphodiesterase-4 (PDE4) inhibitor approved to treat AD, seborrheic dermatitis, and plaque psoriasis. 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. ZORYVE (roflumilast) cream 0.15% is approved by the FDA for the treatment of mild to moderate AD in individuals 6 years of age and older and ZORVYE cream 0.3% for the topical treatment of plaque psoriasis in individuals 6 years of age and older. Another formulation, ZORYVE foam 0.3%, is available for the treatment of seborrheic dermatitis in adults and children ages 9 and older. Roflumilast cream for AD is currently being evaluated at a lower dose of 0.05% for children aged 2 to 5 years. In addition, Arcutis has completed its clinical development program for ZORYVE foam 0.3% for the treatment of scalp and body psoriasis and submitted a supplemental New Drug Application (sNDA) to the FDA in July 2024. INDICATIONSZORYVE cream, 0.3%, is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients 6 years of age and older. ZORYVE cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older. ZORYVE foam, 0.3%, is indicated for the treatment of seborrheic dermatitis in adult and pediatric patients 9 years of age and older. IMPORTANT SAFETY INFORMATIONZORYVE 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 0.3% for plaque psoriasis 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 cream 0.15% for atopic dermatitis include headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%). The most common adverse reactions (≥1%) for ZORYVE foam 0.3% for seborrheic dermatitis include nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%). Please see full Prescribing Information for ZORYVE cream and full Prescribing Information for ZORYVE foam. 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 three 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 real-world use results of roflumilast cream in AD, and the potential for roflumilast cream to advance the standard of care in AD and other 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, and the impact of competition and other important factors discussed in the “Risk Factors” section of our Form 10-K filed with the 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.

临床结果临床3期上市批准

2024-08-28

·GlobeNewswire-Health Care

Arcutis Announces Positive Long-Term Results of Roflumilast Cream 0.05% Show Durable and Improved Efficacy Over Time and Favorable Safety Profile in Treatment of Children Aged 2 to 5 with Mild to Moderate Atopic Dermatitis

Long-term safety and tolerability profile consistent with pivotal data in atopic dermatitis (AD), with no new safety signals observed during 56 weeks of treatmentResults from open-label extension study highlight that 71.9% of patients who rolled over from the roflumilast cream treatment arm in INTEGUMENT-PED achieved EASI-75 at Week 56Arcutis intends to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2025 for roflumilast cream 0.05% WESTLAKE VILLAGE, Calif., Aug. 28, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (NASDAQ: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced results from the INTEGUMENT-OLE long-term open-label study of once-daily roflumilast cream 0.05% demonstrating the durable efficacy and favorable safety profile of roflumilast cream 0.05% in the treatment of mild to moderate AD in children 2 to 5 years old. In the study, roflumilast cream was well-tolerated, with no new safety signals observed during treatment of up to 56 weeks in duration. Efficacy was not only maintained but improved over time, with 71.9% of participants who rolled over from the roflumilast cream 0.05% treatment arm in INTEGUMENT-PED achieving 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) after 56 weeks. “When choosing a therapy for very young children, health care providers and caregivers are looking for treatments that provide both rapid relief and are well-tolerated and suitable for long-term use,” said Adelaide Hebert, MD, professor of dermatology and pediatrics at UTHealth Houston, and INTEGUMENT trial investigator. “These results build upon the findings from the Phase 3 trial of roflumilast cream 0.05% that demonstrated rapid efficacy within the first 4 weeks of treatment, and further showed long-term durable efficacy and tolerability of investigational roflumilast cream, with continued improvement over the course of the long-term study.” In the study, 53.8% of participants who rolled over from the roflumilast cream treatment arm in INTEGUMENT-PED achieved a 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 56 weeks. The long-term study results reinforce the safety and tolerability profile of roflumilast cream 0.05% already seen in the 4-week pivotal INTEGUMENT-PED clinical trial, with no new safety signals observed up to 56 weeks. Overall incidence of adverse events was low, with most being mild to moderate in nature. The most frequently reported adverse events (≥3%) included: upper respiratory tract infection, nasopharyngitis, pyrexia, influenza, COVID-19, and otitis media. Overall, only 3.0% of trial participants discontinued the study due to adverse events. “Roflumilast cream is uniquely formulated with the AD patient in mind, to deliver treatment without sensitizing excipients and irritants, which can often disrupt the skin barrier. We are excited by these results, which reinforce the strength of our ZORYVE product portfolio and specifically demonstrate the long-term efficacy, safety and tolerability profile of our once-daily roflumilast cream for the treatment of pediatric AD,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “Based on these positive results, we are convinced that, if approved, roflumilast cream 0.05% can help provide immediate as well as long-term management of this burdensome skin condition, expanding the treatment population to children down to age 2.” Arcutis intends to submit an sNDA to the FDA in the first quarter of 2025 for roflumilast cream 0.05% for the treatment of AD in individuals ages 2-5 years. ZORYVE® (roflumilast) cream 0.15% is approved for the topical treatment of mild to moderate AD in adults and pediatric patients down to age 6. 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. A total of 562 individuals enrolled in the study after completing the INTEGUMENT-PED Phase 3 trial. The study evaluated monotherapy with roflumilast cream 0.05% 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 maintenance treatment. Participants were able to continue twice weekly maintenance 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 maintenance therapy. The primary objective of the study was to assess the long-term safety of roflumilast cream. Secondary endpoints included vIGA-AD score of 0 or 1 at each assessment, vIGA-AD success defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, and Eczema Area and Severity Index (EASI) score over time. The assessment of vIGA-AD Success and EASI-75 response, as reported here, references baseline of INTEGUMENT-PED. About Atopic DermatitisAD is the most common type of eczema, affecting approximately 9.6 million children and 16.5 million adults in the United States. 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 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 FDA for the topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. Roflumilast cream 0.15% (ZORYVE®) is approved by the U.S. Food and Drug Administration (FDA) for the topical treatment of mild to moderate atopic dermatitis, in patients 6 years of age and older. A lower dose, roflumilast cream 0.05%, was evaluated for children aged 2 to 5 years. INDICATIONSZORYVE cream, 0.3%, is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients 6 years of age and older. ZORYVE cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older. IMPORTANT SAFETY INFORMATION ZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). The most common adverse reactions (≥1%) for ZORYVE cream 0.3% 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 cream 0.15% for atopic dermatitis include headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%). 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 three 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 and timing for roflumilast cream to be approved by the FDA for the treatment of children ages 2 to 5 with AD, the potential to use roflumilast cream in those ages over a long period of time, or chronically, the potential to use roflumilast cream anywhere on the body, and the potential for roflumilast cream to advance the standard of care in AD and other 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, and the impact of competition and other important factors discussed in the “Risk Factors” section of our Form 10-K filed with the 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 Communicationsmedia@arcutis.com InvestorsLatha Vairavan, Vice President, Finance and Corporate Controllerir@arcutis.com

临床结果临床3期上市批准

2024-08-22

·E药经理人

新时代biotech：应对商业化挑战，多多交朋友

2015年起，在biotech融资最火热，而传统pharma遭遇集采、国谈的“谷底”时刻，biotech将作为新兴势力，取代部分pharma地位的观点甚嚣尘上。但随着周期的轮回，pharma又占据了行业C位，而biotech则因资本市场的寒冬，高歌猛进的势头戛然而止。诸多失败案例证明，95%的biotech并不适合发展为biopharma，或者说，发展成biopharma的代价太大，毫无性价比-算下国内某些biopharma的累计融资额：累计亏损：市值的比例，就明白了。这些钱足够塑造几十家优秀biotech，从管线多样性、BD-out、M&A等角度，产出会更大。中国pharma已过于拥挤，再做biopharma，很容易卷成卷心菜-无论多卷，本质还是菜。 01 大环境承压，新上市biotech危中有机在第一波18A大溃败后，新上市biotech面临3个困难： 1、上市募资额少了，上市后也要省着花钱； 2、二级市场投资人越来越看重实打实的东西：产品上市实现销售/利润、对外许可拿到首付款，不能变现的管线-不是好管线。讲故事投资人已经不信； 3、自建销售团队更难：此前几批从传统pharma/MNC跳到biotech的销售队伍，遇到国谈药品杀价+23年反腐，业绩兑现难、岗位也不稳，现在销售人才从上到下，大区-地区-骨干代表，都想在大药企苟着。但这几点对新上市的biotech而言，同时也是机遇： 1、市场薪酬降低、CRO降价，biotech资金使用效率提高； 2、企业审视管线价值，聚焦晚期产品+有BD潜力的产品； 3、药品压价，大药企也面临困局，迫切需要更多产品分摊销售团队固定成本，pharma在积极寻求与biotech达成商业合作。市场统计数据也印证了这一趋势，从2023年开始，BD交易金额已经超越IPO，成为biotech的主要资金来源，且国内biotech与pharma达成商业合作的案例也越来越多。在寒冬里萌发的种子，更坚韧、更能适应环境。今年3月新上市的荃信生物，似乎就在主动迎合趋势，并精准地抓住合作机会： 2024年1月，荃信与健康元就QX008N单抗达成战略合作，健康元将获得QX008N在合作区域（中国大陆、香港、澳门地区）用于呼吸系统等治疗领域所有可开发剂型和适应症的独家研发、生产及商业化权益。 QX008N是一款人源化TSLP抗体，TSLP是哮喘、COPD领域的重磅靶点，此前恒瑞同靶点抗体被GSK以14亿美金收购。 2024年4月，荃信与翰森制药就QX004N单抗达成协议，翰森将获得QX004N在合作区域（中国大陆、香港、澳门及台湾地区）所有可开发剂型和适应症的独家研发、生产及商业化权益。 QX004N是一款IL-23p19抗体，在银屑病、克罗恩病有良好疗效，海外同靶点药物市场超过160亿美金。 2024年7月，荃信与华东医药全资附属公司中美华东就QX500N注射液签订协议，中美华东将深度参与QX005N注射液在授权区域（中国大陆、香港、澳门及台湾）内的后续临床开发并承担相关适应症50%的III期临床开发及后续注册费用，并获得独家市场推广选择权。 QX005N是一款IL-4Rα抗体，海外dupilumab销售额已破100亿美金，市值之大，不用多说。 02 多多与pharma交朋友，提高财务确定性从财务角度，荃信的诸多合作极大降低现金压力，未来实现盈利的确定性大增： 1、合作伙伴承担或分摊研发费用：QX004N与QX008N属于MAH合作，两款药品，合计适应症超过5种，由健康元、翰森负责后续研发，至少省掉了10个亿的研发开支。 QX500N（IL-4Rα）是大品种，公司采取与华东共同开发+CSO合作模式，后端商业权益保留的更多。该合作模式下，华东预期能分担2.5亿元开发/注册费用。多多与pharma合作，是biotech开源节流的秘诀：荃信3起合作，共减少12.5亿元的开发支出，还能持续贡献现金流：翰森制药支付7500万元人民币首付款+不超过10.32亿元的开发、监管及商业化里程碑付款，以及基于销售额的分级特许权使用费；健康元合作也有类似安排。根据最新财报，荃信账面现金+等价物已达6.5亿，足以支持公司穿越产品上市、贡献现金流前的最后一段无人区。 pharma朋友们临床资源广，钱又多，他们出人出钱推进入组，产品后续开发进度，也稳了。 03 精准选择pharma伙伴，提高商业化确定性 biotech寻找pharma合作，除首付款、分成费率等财务指标外，还应该关注pharma与该药品的适配度：好女也怕嫁错郎。自免领域适应症非常细分，即使国内排名靠前的pharma，也是各有擅长科室。荃信的几起交易，选合作方的眼光就非常毒辣： QX008N适应症为哮喘、COPD，而健康元是国内吸入制剂龙头，23年吸入领域销售额17.4亿元，主打就是哮喘和COPD。值得一提的是，健康元已就该产品公示了COPD II期临床，成为国内首家。 QX004N适应症主要是银屑病、克罗恩病，作为百亿药企，翰森销售实力毋庸置疑，自免领域是翰森重点拓展的新领域，而QX004N是翰森引进的第一款自免重磅药，临床开发/上市后将得到大量资源倾斜。 QX500N（IL-4Rα）主要市场在皮肤科，华东拥有丰富的皮科创新药+仿制药产品，包括ZORYVE®（罗氟司特乳膏剂）、ARQ-154（罗氟司特泡沫剂）、Wynzora®乳膏、他克莫司软膏、夫西地酸乳膏等。此前荃信的QX001S（乌司奴biosimilar）亦是与华东医药联合开发，即将获批上市。QX001S主治银屑病，也是皮科。这两个抗体品种很好的完善了华东的皮科产品矩阵，未来基于华东渠道的推广和销售放量，值得期待。至此，荃信生物pipeline里已有近半产品（4/9）找到了pharma合作。回顾荃信的发展之路，充分体现了资本市场对新一代biotech的期待：管线聚焦（自免领域）、资金使用高效（创立9年，累计募资仅14亿元）、对外合作（4款产品达成合作），给资本市场呈现的确实是不同于其他biotech的图景。希望荃信生物带着这份确定性，作为新上市18A企业的代表，在港股市场走出不一样的发展路径。本文转载自：越学习越贫穷《新时代biotech：应对商业化挑战，多多交朋友》一审| 黄佳二审| 李芳晨三审| 李静芝

IPO并购

100 项与罗氟司特相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D05744	罗氟司特	R03DX07	DB01656

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
特应性皮炎	美国	Arcutis Biotherapeutics, Inc.	2024-07-10
脂溢性皮炎	美国	Arcutis Biotherapeutics, Inc.	2023-12-15
斑块状银屑病	加拿大	Arcutis Biotherapeutics, Inc.	2019-12-20
慢性阻塞性肺疾病	欧盟	AstraZeneca AB	2010-07-05
慢性阻塞性肺疾病	冰岛	AstraZeneca AB	2010-07-05
慢性阻塞性肺疾病	列支敦士登	AstraZeneca AB	2010-07-05
慢性阻塞性肺疾病	挪威	AstraZeneca AB	2010-07-05

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
头皮皮肤病	临床3期	美国	Arcutis Biotherapeutics, Inc.	2021-08-24
头皮皮肤病	临床3期	加拿大	Arcutis Biotherapeutics, Inc.	2021-08-24
哮喘	临床3期	美国	AstraZeneca PLC	2003-11-01
哮喘	临床3期	阿根廷	AstraZeneca PLC	2003-11-01
哮喘	临床3期	哥伦比亚	AstraZeneca PLC	2003-11-01
哮喘	临床3期	墨西哥	AstraZeneca PLC	2003-11-01
哮喘	临床3期	秘鲁	AstraZeneca PLC	2003-11-01
慢性哮喘	临床3期	美国	AstraZeneca PLC	2003-04-01
慢性哮喘	临床3期	奥地利	AstraZeneca PLC	2003-04-01
慢性哮喘	临床3期	克罗地亚	AstraZeneca PLC	2003-04-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04445987 (phase 2, CTgov)	临床2期	脂溢性皮炎	408	ARQ-154-203 Roflumilast Foam (Cohort 1 Group 1: ARQ-154-203 Roflumilast Foam 0.3% Without Treatment Gap)	顧選選淵鏇鹽鹽衊廠範(獵築窪憲餘製願鹹膚選) = 鹹衊獵製壓窪觸夢窪窪選觸夢製餘繭膚願範鏇 (遞膚艱壓積構衊遞製糧, 壓醖齋淵艱選蓋範齋餘 ~ 網積獵鬱醖蓋鹹觸衊鹹) 更多	-	2024-06-11
				ARQ-154-203 Roflumilast Foam (Cohort 2 Groups 3 and 4: ARQ-154-203 Roflumilast Foam 0.3% With Treatment Gap)	顧選選淵鏇鹽鹽衊廠範(獵築窪憲餘製願鹹膚選) = 夢襯襯醖鑰衊網廠壓衊選觸夢製餘繭膚願範鏇 (遞膚艱壓積構衊遞製糧, 壓範繭築觸顧蓋夢廠顧 ~ 鹽廠願蓋鹽積簾艱顧壓)
NCT04804605 (INTEGUMENT-OLE, GlobeNewswire) 人工标引	临床3期	特应性皮炎	658	Roflumilast cream 0.15% (INTEGUMENT-1)	遞構簾構壓廠鬱艱憲觸(遞鹹繭願鏇構餘鹹夢夢) = 壓糧壓選網齋餘願範鑰築糧鬱醖壓醖艱壓願醖 (壓遞餘積簾憲鑰鏇範窪 ) 更多	积极	2024-06-10
				Roflumilast cream 0.15% (INTEGUMENT-2)	遞構簾構壓廠鬱艱憲觸(遞鹹繭願鏇構餘鹹夢夢) = 憲艱獵鹹製蓋繭襯窪製築糧鬱醖壓醖艱壓願醖 (壓遞餘積簾憲鑰鏇範窪 ) 更多
Literature 人工标引	N/A	脂溢性皮炎	-	roflumilast foam formulation	-	积极	2024-05-13
NCT04973228 (STRATUM, CTgov)	临床3期	脂溢性皮炎	457	Roflumilast Foam (Roflumilast Foam 0.3%)	糧遞遞糧淵壓構廠積顧(範醖構膚願遞繭遞製範) = 齋糧廠醖願繭餘膚衊願網鬱夢願淵鏇願鹽範鹹 (蓋鏇網憲鏇遞鹹衊憲選, 遞膚窪壓衊蓋憲膚夢鑰 ~ 餘選衊觸網淵製網醖願) 更多	-	2024-03-12
				Vehicle Foam (Vehicle Foam)	糧遞遞糧淵壓構廠積顧(範醖構膚願遞繭遞製範) = 醖構鑰願遞製製糧遞夢網鬱夢願淵鏇願鹽範鹹 (蓋鏇網憲鏇遞鹹衊憲選, 製鬱衊窪艱窪願製壓壓 ~ 夢蓋選鑰壓鹹夢簾膚願) 更多
NCT04845620 (INTEGUMENT-PED, GlobeNewswire) 人工标引	临床3期	特应性皮炎	652	Roflumilast cream 0.05%	蓋簾網簾齋廠餘餘艱網(鑰觸範築製鑰顧膚壓齋) = 網艱蓋廠網願築顧鑰鏇憲艱膚壓範齋獵蓋淵鏇 (製餘糧餘獵網選觸鹹齋 ) 更多	积极	2024-03-11
				Vehicle	蓋簾網簾齋廠餘餘艱網(鑰觸範築製鑰顧膚壓齋) = 鹽膚願艱繭顧淵網壓網憲艱膚壓範齋獵蓋淵鏇 (製餘糧餘獵網選觸鹹齋 ) 更多
NCT04773587 \| NCT04773600 (INTEGUMENT-2 \| INTEGUMENT-II, GlobeNewswire) 人工标引	临床3期	特应性皮炎	-	Roflumilast	網築構選繭淵構齋鏇獵(齋範積夢壓繭壓遞窪窪) = 糧鏇憲構餘獵蓋鹽繭廠糧製蓋鬱鹹襯範選獵製 (窪觸鬱廠遞餘網觸鏇齋 ) 更多	积极	2024-01-14
				Vehicle cream	網築構選繭淵構齋鏇獵(齋範積夢壓繭壓遞窪窪) = 繭繭膚廠夢顧淵顧襯繭糧製蓋鬱鹹襯範選獵製 (窪觸鬱廠遞餘網觸鏇齋 ) 更多
NCT04973228 (STRATUM, GlobeNewswire) 人工标引	临床3期	脂溢性皮炎	189	Roflumilast	鏇壓廠餘願構蓋鏇顧窪(鬱襯構構餘憲構鹹範繭) = 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). 憲襯範積鹽衊積膚顧願 (鹽醖餘選鹽繭憲夢積襯 )	积极	2024-01-14
				Vehicle
NCT04091646 \| NCT04973228 (Trial 203, FDA) 人工标引	临床2/3期	脂溢性皮炎	683	ZORYVE (STRATUM)	蓋鹹艱齋憲製蓋醖選製(鑰獵繭製襯選鹹網範遞) = 繭築網襯淵襯淵網窪窪簾遞積壓選憲衊選夢獵 (餘壓窪簾窪鏇選憲壓繭 ) 更多	积极	2023-12-15
				Vehicle (STRATUM)	蓋鹹艱齋憲製蓋醖選製(鑰獵繭製襯選鹹網範遞) = 鬱獵築壓鹽獵獵壓範淵簾遞積壓選憲衊選夢獵 (餘壓窪簾窪鏇選憲壓繭 ) 更多
NCT04655313 (ARQ-151-215, CTgov)	临床2期	斑块状银屑病	20	ARQ-151 cream 0.3%	選築艱遞蓋餘鬱願膚膚(繭鹹糧範醖蓋艱構觸糧) = 觸構鹹蓋廠艱顧醖範淵蓋襯淵鬱壓夢蓋憲鹽獵 (築糧鏇觸範夢鹽醖製觸, 積觸餘選積鹽遞範網餘 ~ 繭獵膚蓋製夢糧壓構鑰) 更多	-	2023-12-15
NCT04211363 \| NCT04211389 (DERMIS-2, Corporate Publications) 人工标引	临床3期	斑块状银屑病	-	ZORYVE® (roflumilast) cream 0.3%	醖構醖齋壓積齋製糧鹽(衊繭獵遞製夢選鏇壓築) = 網鏇顧襯構壓獵艱繭構繭遞積廠鑰獵繭齋醖壓 (壓襯選衊膚積願鬱壓衊 ) 更多	积极	2023-10-20
				Vehicle	醖構醖齋壓積齋製糧鹽(衊繭獵遞製夢選鏇壓築) = 壓夢獵艱製製蓋鏇顧艱繭遞積廠鑰獵繭齋醖壓 (壓襯選衊膚積願鬱壓衊 ) 更多