Lotilaner Ophthalmic Solution 0.25%: First Approval

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Abstract

Lotilaner ophthalmic solution 0.25% (XDEMVY™), a gamma-aminobutyric acid-gated chloride channel (GABA-Cl) inhibitor selective for mites, is being developed by Tarsus Pharmaceuticals for the treatment of Demodex blepharitis and meibomian gland dysfunction in patients with Demodex lid infestation ( Demodex-induced meibomianitis). On 24 July 2023, lotilaner ophthalmic solution 0.25% received its first approval in the USA for the treatment of Demodex blepharitis. The agent is also currently in phase 3 development for Demodex blepharitis in China and phase 2 development for Demodex-induced meibomianitis in the USA. This article summarizes the milestones in the development of lotilaner ophthalmic solution 0.25% leading to this first approval for the treatment of Demodex blepharitis in the USA.

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The online version contains supplementary material available at 10.1007/s40265-023-01947-9.

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The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels.

Yoshihisa Ozoe, Miho Asahi, Fumiyo Ozoe … (2010)

A structurally unique isoxazoline class compound, A1443, exhibits antiparasitic activity against cat fleas and dog ticks comparable to that of the commercial ectoparasiticide fipronil. This isoxazoline compound inhibits specific binding of the gamma-aminobutyric acid (GABA) receptor channel blocker [(3)H]4'-ethynyl-4-n-propylbicycloorthobenzoate (EBOB) to housefly-head membranes, with an IC(50) value of 455pM. In contrast, the IC(50) value in rat-brain membranes is>10muM. To study the mode of action of this isoxazoline, we utilized MdGBCl and MdGluCl cDNAs, which encode the subunits of housefly GABA- and glutamate-gated chloride channels, respectively. Two-electrode voltage clamp electrophysiology was used to confirm that A1443 blocks GABA- and glutamate-induced chloride currents in Xenopus oocytes expressing MdGBCl or MdGluCl channels, with IC(50) values of 5.32 and 79.9 nM, respectively. Blockade by A1443 was observed in A2'S-MdGBCl and S2'A-MdGluCl mutant channels at levels similar to those of the respective wild-types, and houseflies expressing A2'S-MdGBCl channels were as susceptible to A1443 as standard houseflies. These findings indicate that A1443 is a novel and specific blocker of insect ligand-gated chloride channels. Copyright 2009 Elsevier Inc. All rights reserved.

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High prevalence of Demodex in eyelashes with cylindrical dandruff.

Ying-Ying Gao, Mario A Di Pascuale, Wei Li … (2005)

To determine the prevalence of Demodex in eyelashes with cylindrical dandruff (CD). A modified sampling and counting method was applied to 55 clinical cases. Patients were divided in to group A (n = 20) with diffuse CD, group B (n = 12) with sporadic CD, and group C (n = 23) with clean lashes or greasy scales, of which the latter was divided into subgroup C1 (n = 15) without lid hygiene and subgroup C2 (n = 8) using daily lid hygiene for the past year. Each patient underwent a routine complete eye examination and modified counts of Demodex. Demodex was found in all group A and B patients (n = 32) with CD, which was significantly higher than the 22% of group C patients (n = 23) without CD (P < 0.001). The Demodex counts were 4.1 +/- 1.0 and 2.0 +/- 1.2 per epilated lash with retained CD, significantly higher than the 0.2 +/- 0.5 and 0.2 +/- 0.4 per lash without retained CD in groups A and B, respectively (each P < 0.001) and than the 0.01 +/- 0.09 and 0.12 +/- 0.41 per lash in subgroups C1 and C2, respectively (each P < 0.001). Demodex was still found in CD fragments left on the lid skin after epilation. Five Demodex brevis mites were found among the 422 Demodex specimens. The modified sampling and counting method showed that the prior controversy regarding Demodex has resulted from miscounting and confirmed that lashes with CD are pathognomonic for ocular Demodex infestation. Lid hygiene with shampoo reduces Demodex counts but does not eradicate the mites.

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Demodex blepharitis: clinical perspectives

Stephanie Fromstein, Jennifer S. Harthan, Jaymeni Patel … (2018)

Demodex folliculorum and Demodex brevis are two mites which infest the human eye and which may, in excess, lead to a wide range of anterior segment findings. Demodex mites have been implicated in anterior and posterior blepharitis, blepharoconjunctivitis, blepharokeratitis, and beyond. Due to significant overlap with other anterior segment conditions, Demodex infestation remains underdiagnosed and undertreated. Definitive diagnosis can be made with lash sampling, and the most common mode of treatment is with tea tree oil in varying concentrations. This article summarizes elements of pathogenesis, diagnosis, and management critical to clinical care of this common condition.

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Contributors

Yahiya Y. Syed: dru@adis.com

Journal

Journal ID (nlm-ta): Drugs

Journal ID (iso-abbrev): Drugs

Title: Drugs

Publisher: Springer International Publishing (Cham )

ISSN (Print): 0012-6667

ISSN (Electronic): 1179-1950

Publication date (Electronic): 16 October 2023

Publication date PMC-release: 16 October 2023

Publication date (Print): 2023

Volume: 83

Issue: 16

Pages: 1537-1541

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Springer Nature, ( https://ror.org/029zamy29) Mairangi Bay, Private Bag 65901, Auckland, 0754 New Zealand

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Publisher ID: 1947

DOI: 10.1007/s40265-023-01947-9

PMC ID: 10624734

PubMed ID: 37843754

SO-VID: c90d4f9f-765e-4cb0-9811-42cf07f9ffb3

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Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

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Lotilaner Ophthalmic Solution 0.25%: First Approval

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The antiparasitic isoxazoline A1443 is a potent blocker of insect ligand-gated chloride channels.

High prevalence of Demodex in eyelashes with cylindrical dandruff.

Demodex blepharitis: clinical perspectives

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