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Drugs Nov 2023Lotilaner ophthalmic solution 0.25% (XDEMVY™), a gamma-aminobutyric acid-gated chloride channel (GABA-Cl) inhibitor selective for mites, is being developed by Tarsus... (Review)
Review
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.
Topics: Humans; Mite Infestations; Blepharitis; Ophthalmic Solutions; Eye Infections, Parasitic; Meibomitis
PubMed: 37843754
DOI: 10.1007/s40265-023-01947-9 -
Drugs Feb 2017Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen... (Review)
Review
Lifitegrast is a novel small molecule integrin antagonist that blocks the binding of intercellular adhesion molecule 1 (ICAM-1) to lymphocyte function-associated antigen 1 (LFA-1). Lifitegrast ophthalmic solution 5% (Xiidra™) was recently approved in the USA for the treatment of dry eye disease. The efficacy of lifitegrast ophthalmic solution 5% was compared with vehicle in a 12-week phase 2 study and three 12-week phase 3 studies (OPUS-1, OPUS-2 and OPUS-3) in patients with dry eye disease. Taken as a whole, results of these trials support the treatment effect of lifitegrast ophthalmic solution 5% in improving a symptom of dry eye disease (i.e. the change from baseline to day 84 in the eye dryness visual analogue scale score) and a sign of dry eye disease (i.e. the change from baseline to day 84 in the inferior corneal fluorescein staining score). Lifitegrast ophthalmic solution 5% was generally well tolerated. In conclusion, lifitegrast ophthalmic solution 5% provides a new option for the treatment of dry eye disease.
Topics: Dry Eye Syndromes; Humans; Ophthalmic Solutions; Phenylalanine; Sulfones
PubMed: 28058622
DOI: 10.1007/s40265-016-0681-1 -
Drugs Apr 2024Perfluorohexyloctane ophthalmic solution (Miebo) is a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane that is approved in... (Review)
Review
Perfluorohexyloctane ophthalmic solution (Miebo) is a single-entity, water-, steroid- and preservative-free, first-in-class semifluorinated alkane that is approved in the USA for the treatment of the signs and symptoms of dry eye disease (DED). DED is often linked with meibomian gland dysfunction (MGD), which causes an excessive evaporation of tears. Perfluorohexyloctane ophthalmic solution stabilizes the lipid layer of the tear film and inhibits tear evaporation by forming a monolayer at the air-liquid interface. In the phase III GOBI and MOJAVE trials in adults with DED associated with MGD, one drop of perfluorohexyloctane ophthalmic solution instilled in each eye four times daily over 8 weeks resulted in statistically significant and clinically meaningful improvements in the signs and symptoms of DED compared with hypotonic saline (0.6%). The agent was generally well tolerated, with most ocular adverse events being mild or moderate in severity. The efficacy and tolerability of perfluorohexyloctane ophthalmic solution was sustained for up to 52 weeks in an extension study (KALAHARI). As the first and currently the only prescription treatment approved in the USA directly addressing the pathophysiology of excessive tear evaporation, perfluorohexyloctane ophthalmic solution is a valuable emerging option for the management of DED.
Topics: Humans; Ophthalmic Solutions; Fluorocarbons; Dry Eye Syndromes
PubMed: 38554243
DOI: 10.1007/s40265-024-02016-5 -
Cornea Apr 2023The purpose of this study was to evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25%, compared with vehicle for the treatment of Demodex blepharitis. (Randomized Controlled Trial)
Randomized Controlled Trial
Lotilaner Ophthalmic Solution, 0.25%, for the Treatment of Demodex Blepharitis: Results of a Prospective, Randomized, Vehicle-Controlled, Double-Masked, Pivotal Trial (Saturn-1).
PURPOSE
The purpose of this study was to evaluate the safety and efficacy of lotilaner ophthalmic solution, 0.25%, compared with vehicle for the treatment of Demodex blepharitis.
METHODS
In this prospective, randomized, controlled, double-masked, phase 2b/3 clinical trial, 421 patients with Demodex blepharitis were randomly assigned in a 1:1 ratio to receive either lotilaner ophthalmic solution, 0.25% (study group), or vehicle without lotilaner (control group) bilaterally, twice daily for 43 days. Patients were evaluated at days 8, 15, 22, and 43. Outcome measures were complete collarette cure (collarette grade 0), clinically meaningful collarette cure (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes/erythema), and drop comfort. Adverse events were also evaluated.
RESULTS
At day 43, the study group achieved a statistically significantly higher proportion of patients with clinically meaningful collarette cure (81.3% vs. 23.0%; P < 0.0001), complete collarette cure (44.0% vs. 7.4%; P < 0.0001), mite eradication (67.9% vs. 17.6%; P < 0.0001), erythema cure (19.1% vs. 6.9%; P = 0.0001), and composite cure (13.9% vs. 1.0%; P < 0.0001) than the control group. Nearly 92.0% of patients rated the study drop as neutral to very comfortable. All ocular adverse events in the study group were mild, with the most common being instillation site pain.
CONCLUSIONS
Twice-daily treatment with a novel lotilaner ophthalmic solution, 0.25% for 43 days, is safe and effective for the treatment of Demodex blepharitis compared with the vehicle control.
Topics: Humans; Ophthalmic Solutions; Prospective Studies; Double-Blind Method; Blepharitis
PubMed: 35965392
DOI: 10.1097/ICO.0000000000003097 -
Journal of Pharmacy & Pharmaceutical... 2019Dry eye disease (DED) is a common inflammatory disorder of the ocular surface. Millions of people are affected by DED worldwide. Lifitegrast is a novel drug designed to... (Review)
Review
Dry eye disease (DED) is a common inflammatory disorder of the ocular surface. Millions of people are affected by DED worldwide. Lifitegrast is a novel drug designed to inhibit DED-associated ocular inflammation. Four clinical trials have shown that lifitegrast is well tolerated and effective in improving symptoms and signs of DED over 12 weeks. A fifth trial showed long-term safety over 1 year. Lifitegrast has been in clinical use for more than one year in the United States and was recently approved in Canada (in December 2017). In this review, we discuss lifitegrast's novel mechanism of action and provide an overview of its clinical trial program.
Topics: Animals; Clinical Trials as Topic; Dry Eye Syndromes; Humans; Ophthalmic Solutions; Phenylalanine; Sulfones; Treatment Outcome
PubMed: 30636670
DOI: 10.18433/jpps29895 -
Expert Review of Clinical Pharmacology Aug 2022Ocular redness, or conjunctival hyperemia, is a common ophthalmic sign associated with reduced quality of life. For redness without apparent underlying pathology,... (Review)
Review
INTRODUCTION
Ocular redness, or conjunctival hyperemia, is a common ophthalmic sign associated with reduced quality of life. For redness without apparent underlying pathology, topical ophthalmic decongestants have been widely used.
AREAS COVERED
Brimonidine tartrate was approved in 2017 as a topical vasoconstrictor at a 0.025% concentration for relief of ocular redness. Since then, investigators have reported on efficacy and safety findings from studies evaluating low-dose brimonidine for reducing ocular redness.
EXPERT OPINION
Brimonidine is highly selective for α-adrenergic receptors. Clinical trials have so far shown that the drug in low doses significantly reduces ocular redness in comparison to vehicle for up to 8 hours. Brimonidine-treated eyes did not present side effects of other vasoconstrictors, such as hypotension, cardiac arrhythmia, or drowsiness. Ocular adverse events, such as allergic reactions and redness rebound, were also minimal. In this review, we examine in detail published literature on the mechanism of brimonidine tartrate and its efficacy and safety in relieving conjunctival hyperemia.
Topics: Adrenergic alpha-Agonists; Brimonidine Tartrate; Erythema; Humans; Hyperemia; Nasal Decongestants; Ophthalmic Solutions; Quality of Life; Quinoxalines; Receptors, Adrenergic
PubMed: 35951740
DOI: 10.1080/17512433.2022.2112948 -
Advanced Science (Weinheim,... Jan 2023Diabetic retinopathy (DR) is the leading cause of vision loss in working age population. Intravitreal injection of anti-VEGF antibody is widely used in clinical...
Diabetic retinopathy (DR) is the leading cause of vision loss in working age population. Intravitreal injection of anti-VEGF antibody is widely used in clinical practice. However, about 27% of patients show poor response to anti-VEGF therapy and about 50% of these patients continue to have macular thickening. Frequent intravitreal injections of antibody may increase the chance of endophthalmitis and cause visual loss or even blindness once happened. Therefore, there is a greatly urgent need for novel noninvasive target to treat DR clinically. Here, the formulation of a smart supramolecular peptide (SSP) eye drop for DR treatment that is effective via specifically identifying and capturing soluble semaphorin 4D (sSema4D), a strongly pro-angiogenesis and exudates factor, is reported. The SSP nanostructures encapsulate sSema4D so that all biological effects mediated by three receptors of sSema4D are inhibited, thereby significantly alleviating pathological retinal angiogenesis and exudates in DR. Moreover, it is found that combination of SSPs eye drop and anti-VEGF injection shows better therapeutic effect over anti-VEGF treatment alone. Overall, SSP eye drop provide an alternative and effective method for noninvasive treatment for DR.
Topics: Humans; Diabetic Retinopathy; Angiogenesis Inhibitors; Vascular Endothelial Growth Factor A; Ophthalmic Solutions; Peptides; Intravitreal Injections; Diabetes Mellitus
PubMed: 36437109
DOI: 10.1002/advs.202203351 -
Advances in Therapy Jul 2012There has been rapid progress in our understanding of dry eye pathogenesis, as well as the development of improved diagnostic clinical tests. Various types of dry eye... (Review)
Review
INTRODUCTION
There has been rapid progress in our understanding of dry eye pathogenesis, as well as the development of improved diagnostic clinical tests. Various types of dry eye treatment drugs have been developed. This review summarizes the basic and clinical research carried out in the development of diquafosol for ophthalmic use.
RESULTS
Diquafosol is a dinucleotide, purinoreceptor P2Y(2) receptor agonist. Basic pharmacological studies have shown that it acts on P2Y(2) receptors at the ocular surface, to promote tear and mucin secretion via elevated intracellular Ca(2+) concentrations. Diquafosol also improves tear and mucin secretion in experimental dry eye models. Based on the results of laboratory experiments, the authors conducted a series of clinical studies in patients with dry eye disease. Diquafosol was effective in the treatment of dry eye disease at an optimal dose of 3% six times a day. In comparison to commercially available 0.1% sodium hyaluronate ophthalmic solution, 3% diquafosol ophthalmic solution showed non-inferiority in improving corneal fluorescein staining scores and superiority in improving keratoconjunctival Rose Bengal staining scores.
CONCLUSIONS
Diquafosol ophthalmic solution has a novel mechanism of action that is characterized by its stimulatory effects on tear and mucin secretion. This drug has the potential to be effective in patients with tear film instability and short break-up time type of dry eye, which are essential factors in dry eye pathogenesis.
Topics: Dry Eye Syndromes; Humans; Mucins; Ophthalmic Solutions; Polyphosphates; Purinergic P2Y Receptor Agonists; Tears; Treatment Outcome; Uracil Nucleotides
PubMed: 22843206
DOI: 10.1007/s12325-012-0033-9 -
Clinical Drug Investigation Aug 2015The nonsteroidal anti-inflammatory drug bromfenac has recently been reformulated with a lower pH to facilitate a reduction in the concentration of bromfenac (to 0.07%)... (Review)
Review
The nonsteroidal anti-inflammatory drug bromfenac has recently been reformulated with a lower pH to facilitate a reduction in the concentration of bromfenac (to 0.07%) while ensuring an ocular bioavailability similar to that of the 0.09% formulation. Bromfenac ophthalmic solution 0.07% (hereafter referred to as bromfenac 0.07%) [Prolensa(®)] is a once-daily topical ophthalmic solution available in the USA and Canada for the treatment of postoperative inflammation and the reduction of ocular pain in patients who have undergone cataract surgery. In an integrated analysis of two multicentre, phase III studies, bromfenac 0.07% was significantly more effective than placebo in reducing ocular inflammation and pain. In these studies, bromfenac 0.07% was well tolerated, with significantly lower incidences of adverse events, and adverse events affecting the study eye than with placebo. The most common adverse events in the study eye (eye pain, anterior chamber inflammation, foreign body sensation, photophobia, conjunctival hyperaemia and corneal oedema) occurred in numerically fewer bromfenac 0.07% than placebo recipients. Thus, current evidence suggests once-daily bromfenac 0.07% extends the treatment options currently available for the management of postoperative inflammation and pain following cataract surgery.
Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Benzophenones; Bromobenzenes; Cataract Extraction; Female; Humans; Inflammation; Male; Middle Aged; Ophthalmic Solutions; Pain, Postoperative
PubMed: 26177719
DOI: 10.1007/s40261-015-0309-3 -
Clinical & Experimental Optometry Nov 2019Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP)... (Review)
Review
Latanoprostene bunod (LBN) ophthalmic solution 0.024% is a novel, once-daily, nitric oxide-donating prostaglandin analogue for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma and ocular hypertension. The IOP-lowering actions of LBN are mediated by dual mechanisms of the molecule for increasing aqueous humour outflow. The prostaglandin analogue moiety (latanoprost acid) increases uveoscleral outflow, whereas nitric oxide, released by the nitric oxide-donating moiety (butanediol mononitrate), increases outflow through the trabecular meshwork and the Schlemm's canal. The clinical efficacy and safety of LBN 0.024% in patients with open-angle glaucoma or ocular hypertension were established in two similarly designed, double-masked, pivotal phase 3 studies, APOLLO and LUNAR, the pooled three-month efficacy phase of which demonstrated significantly greater IOP-lowering of once-daily LBN 0.024% over twice-daily timolol 0.5% at all time points. Additional support for the IOP-lowering effects of LBN 0.024% was provided by two phase 2 studies in patients with open-angle glaucoma or ocular hypertension (a dose ranging study versus latanoprost and a 24-hour IOP crossover study versus timolol) and a phase 1 study of healthy volunteers with IOP in the normal range. In addition, long-term efficacy and safety were demonstrated in the open-label safety-extension phases of the phase 3 pivotal studies and a phase 3 52-week open-label study of patients with open-angle glaucoma (including normal-tension glaucoma) or ocular hypertension. In conclusion, LBN 0.024% has demonstrated both short-term and long-term IOP-lowering efficacy in patients with open-angle glaucoma or ocular hypertension, including in healthy volunteers and patients with IOP in the normal range, without apparent clinically-limiting safety or tolerability concerns.
Topics: Animals; Clinical Trials as Topic; Glaucoma, Open-Angle; Humans; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F, Synthetic
PubMed: 30614563
DOI: 10.1111/cxo.12853