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ADIS DRUG Q&A Cationorm (cationic emulsion eye drops) in dry eye disease: a gu

ADIS DRUG Q&A Cationorm (cationic emulsion eye drops) in dry eye disease: a guide to its use Katherine A. Lyseng-Williamson1 Published online: 30 June 2016 Springer International Publishing Switzerland 2016 Abstract Cationorm is a unique preservative-free option for the treatment of the symptoms of dry eye that offers some advantages over conventional artiﬁcial tears. The electrostatic interaction between the positively charged Cationorm emulsion and the negatively charged cells on the ocular surface prolongs the residence time on the ocular surface. Moreover, as an oily emulsion, Cationorm aug- ments all three layers of tear ﬁlm (i.e. lipid layer, aqueous coating and mucin layer), thereby stabilizing the tear ﬁlm and providing beneﬁcial moisturizing and lubricating effects. Overall, the efﬁcacy and tolerability/safety proﬁles of Cationorm in treating mild to severe dry eye disease in clinical trials are similar to, or better than, those of other artiﬁcial tears. Adis evaluation of Cationorm in dry eye disease Unique cationic emulsion that provides rapid and sustained relief of dry eye symptoms Supports all three layers of tear ﬁlm (i.e. lipid layer, aqueous coating and mucin layer), thereby stabilizing the tear ﬁlm and moisturizing and lubricating the eye Equally or more effective than comparator artiﬁcial tears in treating mild to severe dry eye symptoms Does not cause blurred vision after application Very well tolerated What is the rationale for developing Cationorm? Dry eye disease is characterized by an inadequate quality or volume of tears, leading to the chronic irritation and inﬂammation of the ocular surface [1–3]. A relatively common condition, dry eye disease affects & 5–35 % of adults, (with an increased prevalence in older adults and in women) [4, 5], and has a substantial effect on visual function and health-related quality of life (HR-QOL) [2, 3, 6]. The two major subtypes of dry eye disease are aqueous- deﬁcient dry eye (caused by the insufﬁcient production of tears by the lacrimal glands) and evaporative dry eye (caused by the excessive evaporation of tears) [7]. Eva- porative dry eye appears to be more common subtype, and is commonly related to meibomian gland dysfunction (MGD) [7, 8]. The two major subtypes of dry eye are not mutually exclusive and present with similar ocular symp- toms, such as dryness, itching, irritation, foreign-body sensation and visual disturbance, with some patients showing signs of damage to the ocular surface [3, 7, 9]. Some patients, especially those who present with more severe symptoms early in the course of the disease, will experience a worsening of ocular surface symptoms, vision-related symptoms and HR-QOL over time [10]. Although a number of topical treatments for dry eye are available, most are aqueous tear substitutes that provide lubrication, hydration and protection, but that do not improve the stability of the tear ﬁlm or prevent the excessive evaporation of tears [9, 11]. There is a thera- peutic need to develop new products to treat dry eye that stabilize the tear ﬁlm and the tear ﬁlm lipid layer [12], as well as providing moisturizing and lubricating effects. Cationorm is a cationic emulsion-based formulation that has been developed to meet this need. & Katherine A. Lyseng-Williamson dtp@adis.com 1 Springer, Private Bag 65901, Mairangi Bay, 0754 Auckland, New Zealand Drugs Ther Perspect (2016) 32:317–322 DOI 10.1007/s40267-016-0319-0 How does Cationorm work? The formulation of Cationorm differs from those of other artiﬁcial tears used to treat dry eye, in that it is a preser- vative-free cationic oil-in-water nanoemulsion that sup- ports all there layers of the tear ﬁlm [13–15]. Cationorm has a viscosity similar to that of normal human tears, and does not include any active ingredients. Its beneﬁcial properties on relieving the symptoms of dry eye are pro- vided by the hypotonic cationic emulsion itself [the ingredients of which include cetalkonium chloride, tylox- apol and poloxamer 188 (polar surfactant compounds,) as well as glycerol trishydrochloride, tromethamine and puriﬁed water] [13–15]. Cationic nanoemulsion technology (i.e. Novasorb) is used to produce an aqueous emulsion made up of positively-charged lipid nanodroplets, which are attracted to the negatively-charged ocular surface and are distributed evenly over the ocular surface immediately after administration [14, 15]. The electrostatic attraction between the cationic nanoemulsion and the ocular surface prolongs the resi- dence time on the ocular surface, thereby providing long- lasting relief of the symptoms of dry eye. Cationorm provides support to the all three levels of the tear ﬁlm in patients with dry eye in the following manner [13–15]: • Lipid layer Adds lipids to the external lipid layer, thereby stabilizing the tear ﬁlm and preventing evap- oration of tears from the ocular surface. For example, in a study of the interactions between Cationorm and healthy human meibum ﬁlms [12], Cationorm enhanced the structure and surface properties of the meibum ﬁlm by simultaneously supplementing the non- polar lipid stratum with its oil phase and supplementing the aqueous tear/tear ﬁlm lipid layer with spreading agents (i.e. the polar surfactant compounds cetalkonium chloride, poloxamer and tyloxapol). • Aqueous coating Allows optimal spreading and pro- longed resident time of the emulsion on the ocular surface, thereby providing long-lasting moisturization. • Mucin layer Ensures the wetting and adherence of the tear ﬁlm to ocular surfaces, and provides prolonged lubrication, thereby enabling the protection and healing of the corneal epithelium. As previously reviewed [14, 15], the ocular beneﬁts and/ or safety of the cationic emulsion has been shown in a number of preclinical in vitro and animal studies. For example, in a rat model of corneal scraping, Cationorm was well tolerated, restored an adequately hydrated ocular surface environment and, unlike the other evaluated arti- ﬁcial tears (i.e. Systane Balance, Optive and Vismed), appeared to have direct anti-inﬂammatory properties [16]. Moreover, compared with artiﬁcial tear formulations con- taining the preservative benzalkonium chloride (BAK), preservative-free Cationorm exhibited good tolerability on human corneal epithelial cell cultures, even with longer than realistic exposure times [17]. For whom is Cationorm indicated? Cationorm is indicated to provide relief of dry eye symptoms, such as stinging, itching or burning eyes, or foreign-body sensation in the eyes [13]. It may be used to treat dry eye symptoms regardless of when the symptoms are caused by extrinsic or intrinsic factors [13]. Table 1 provides a summary of the use of Cationorm to treat dry eye, based on the patient information in Germany [13], as representative of its use in the countries in which it is available. What is the clinical efﬁcacy of Cationorm? The efﬁcacy of Cationorm in the treatment of dry eye has been shown in several randomized, controlled, multicentre clinical trials [18–21]. One trial has been fully published [19]; results of other trials are submitted or available as abstracts [18, 20] or a slide presentation [21]. An exploratory single-masked trial in 72 patients with moderate dry eye syndrome found that formulations of Cationorm containing 1 or 2 % parafﬁn oil provided clinically relevant improvements in ocular signs and symptoms (as assessed by changes from baseline in Schirmer’s test, tear break-up time and lissamine green global score results), with improvements being more marked in the Cationorm 1 % group than in the groups receiving Cationorm 2 % or normal saline [18]. Table 2 provides a brief summary of the design and key results of the three subsequent trials of Cationorm versus other commercially available artiﬁcial-tear eye drops in patients with dry eye disease. Baseline inclusion values were determined after a washout period, during which patients received normal saline eye drops [19–21]. Across these three trials, treatment with Cationorm was associated with improvements from baseline in many outcomes related to dry eye, including tear break-up time [19, 20], tear ﬁlm osmolarity [20], lissamine green staining scores [19], Schirmer’s test values [19], corneal clearing/ staining [19–21], ocular staining [21] and various other signs and/or symptoms of dry eye [19–21] (Table 2). In addition to its lubricating, moisturizing and tear-ﬁlm sta- bilizing effects, Cationorm was associated with improvements from baseline in HR-QOL subscale scores 318 [21], and was assessed by investigators to have ‘satisfac- tory’ efﬁcacy in [ 80 % of patients [19, 21]. Overall, the efﬁcacy of Cationorm in treating mild to severe dry eye disease was similar to, or greater than, the artiﬁcial-tear eye drops used as comparator in these studies (i.e. Refresh, a solution containing polyvinyl alcohol/ povidone [19]; Optive, a solution containing sodium carboxylmethylcellulose sodium and glycerine [20]; Emustil, an emulsion containing soybean oil and natural phospholipids [20]; and Vismed, a solution containing 0.18 % hyaluronic acid [21]) [Table 2]. In the fully published trial in patients with mild to moderate dry eye disease, both Cationorm and Refresh improved the signs and symptoms of mild to moderate dry eye disease as early as day 7 of the trial, with improvements from baseline being sustained or increased at day 28 (Table 2) [19]. Cationorm stabilized the integrity of the tear ﬁlm to a greater extent than Refresh, as shown by the signiﬁcant between- group-differences (BGD) at day 28 in tear break-up time and lissamine green staining scores, as well as eyelid erythema, eye dryness and total ocular symptom scores (Table 2). uploads/Sante/ cationorm-guide.pdf