Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study

Ohba, Fuminori; Matsuki, Shunji; Imayama, Shuhei; Matsuguma, Kyoko; Hojo, Seiichiro; Nomoto, Maiko; Akama, Hideto

doi:10.3109/09546634.2016.1157257

Cited by 37 publications

(25 citation statements)

References 24 publications

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“…The selective PDE-4 inhibitor RVT-501 has been shown to be clinically active in atopic dermatitis, with most common AE being local site reactions, nasopharyngitis, urticaria and acne [168][169][170][171]. The potential utility of this compound in lung cancer has also been demonstrated in a murine model of pulmonary inflammation, where an inhaled dry powdered formulation of E6005 when adminstered to mice resulted in suppression of neutrophilic pulmonary inflammation [172].…”

Section: E6005 (Rvt-501) (Eisai / Roivant)mentioning

confidence: 95%

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

Joerger

Finn

Cuffe

et al. 2016

Expert Opinion on Therapeutic Targets

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There is strong pharmaceutical development of agents targeting the IL-17-TH17 pathway for the treatment of psoriasis (Ps) and psoriatic arthritis (PsA). Lung cancer accounts for 28% of all cancer-related deaths worldwide, and roughly 80% of patients with newly-diagnosed non-small cell lung cancer (NSCLC) present with metastatic disease, with a poor prognosis of around 12 months. Therefore, there is a high unmet medical need for the development of new and potent systemic treatments in this deadly disease. The emergence of immunotherapies such as anti-PD-1 or anti-PDL1 as candidate therapies in non-small cell lung cancer (NSCLC) indicates that targeting critical immuno-modulatory cytokines including those within the IL-17-Th1/Th17 axis may have proven benefit in the treatment of lung cancer. Areas covered: In this review we describe the current evidence for aberrant IL-17-Th1/Th17 settings in cancer, particularly with regard to targeting this axis in NSCLC. We further discuss the current agents under pharmaceutical development which could potentially target this axis, and discuss the current limitations and areas of concern regarding the use of these in lung cancer. Expert opinion: Current evidence suggests that moving forward agents targeting the IL-17-Th1/Th17 pathway may have novel new oncoimmunology indications in the treatment paradigm for NSCLC.

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Section: E6005 (Rvt-501) (Eisai / Roivant)mentioning

confidence: 95%

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

Joerger

Finn

Cuffe

et al. 2016

Expert Opinion on Therapeutic Targets

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“…PDE‐4 inhibitors will be available in both topical and oral forms. Topical PDE‐4 inhibitors, that is, Crisaborole, E6005 and DRM02 (ClinicalTrials.gov Identifier: NCT01993420) show promising results in clinical studies (details are shown in Table ). In addition, apremilast, an oral PDE‐4 inhibitor, achieved a decrease in EASI in a phase II study for AD …”

Section: New Drugs For the Treatment Of Admentioning

confidence: 99%

The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis

Otsuka

Nomura

Rerknimitr

et al. 2017

Immunological Reviews

134

105

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Atopic dermatitis (AD) is a chronic skin disorder characterized by pruritus and recurrent eczematous lesions that are accompanied by T-helper (Th)2-dominated inflammation. AD Etiology is not yet completely understood, but it is multifactorial. Moreover, the disease is characterized by complex interactions between genetic and environmental factors, such as skin barrier dysfunctions, allergy/immunity, and pruritus. For example, filaggrin is a key protein involved in skin barrier function. Th2 cells produce interleukin (IL)-31, which provokes pruritus, and other Th2 cytokines decrease filaggrin expression by keratinocytes. Dupilumab has recently been developed for AD treatment; its mechanism of action is to bind to IL-4 receptor α and inhibit downstream signaling induced by IL-4 and IL-13. This review summarizes the etiopathogenesis of AD and provides the rationale for selecting a novel targeted therapy.

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“…Unlike crisaborole, none of these investigational drugs contains boron; however, like crisaborole, they generally fall under the 500‐Dalton rule in terms of molecular weight, allowing for skin penetration (Figure ) . In addition, although promising results have been published for some of these agents, none has been evaluated in phase 3 studies.…”

Section: Pde4 Inhibitors Currently Available and In Development For Admentioning

confidence: 99%

“…E6005/RVT‐501 is a topical PDE4 inhibitor that has been evaluated in several phase 1/2 studies. Results have been promising in children and adults in Japan . For example, at 0.03% and 0.2% strengths, a significant reduction in Scoring of Atopic Dermatitis (SCORAD) index score was observed in adults aged 20‐60 years .…”

Section: Pde4 Inhibitors Currently Available and In Development For Admentioning

confidence: 99%

The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition

Guttman‐Yassky

Hanifin

Boguniewicz

et al. 2018

Experimental Dermatology

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Atopic dermatitis (AD) is a highly prevalent, chronic inflammatory skin disease that affects children and adults. The pathophysiology of AD is complex and involves skin barrier and immune dysfunction. Many immune cytokine pathways are amplified in AD, including T helper (Th) 2, Th22, Th17 and Th1. Current treatment guidelines recommend topical medications as initial therapy; however, until recently, only two drug classes were available: topical corticosteroids (TCSs) and topical calcineurin inhibitors (TCIs). Several limitations are associated with these agents. TCSs can cause a wide range of adverse effects, including skin atrophy, telangiectasia, rosacea and acne. TCIs can cause burning and stinging, and the prescribing information lists a boxed warning for a theoretical risk of malignancy. Novel medications with new mechanisms of action are necessary to provide better long‐term control of AD. Phosphodiesterase 4 (PDE4) regulates cyclic adenosine monophosphate in cells and has been shown to be involved in the pathophysiology of AD, making it an attractive therapeutic target. Several PDE4 inhibitors are in clinical development for use in the treatment of AD, including crisaborole, which recently became the first topical PDE4 inhibitor approved for treatment of mild to moderate AD. This review will further describe the pathophysiology of AD, explain the possible role of PDE4 in AD and review PDE4 inhibitors currently approved or being investigated for use in AD.

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Efficacy of a novel phosphodiesterase inhibitor, E6005, in patients with atopic dermatitis: An investigator-blinded, vehicle-controlled study

Abstract: E6005 ointment showed anti-inflammatory efficacy in adult patients with atopic dermatitis.

Cited by 37 publications

References 24 publications

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

The IL-17-Th1/Th17 pathway: an attractive target for lung cancer therapy?

The interplay between genetic and environmental factors in the pathogenesis of atopic dermatitis

The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition

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