Clinical Case Studies

Professional Disclosure

Alcon: Research Grants, Speaker
Allergan: Grants, Speaker, Advisory Board, Media Spokesman
Alacrity Biosciences: Advisory Board, Research Grants
Bausch & Lomb: Research Grants, Speaker, Advisory Boards
EyeRx Research: Research Grants, Shareholder
Isis Pharmaceuticals: Research, Advisory Board
Inspire Pharmaceuticals: Research, Speaker, Advisory Board
Ista: Research Grants
Insite: Research Grants
Lumenis: Speaker
Lux Biosciences: Research Grants
Novartis: Speaker, Advisory Board
OcuCure: Advisory Board, Research Grants, Shareholder
Ciba-Vision: Speaker, Research Grants
Pfizer: Research, Speaker
Santen: Research, Speaker, Advisory Board
Science Based Health: Research, Advisory, Media Spokesman
Senju: Research Grants
Talia Technology: Speaker, Advisory Board
Vistakon: Speaker, Advisory Board

32 yo Hispanic male

Recalcitrant HSV keratitis OD
Trifluridine x 18 days, now qid
Persistent epithelial healing defect
Acuity 20/50
Zirgan started tid
Defect healed 10 days
Acuity 20/20-2

55 yo white female

Recurrent HSV stromal keratitis OS
- Famciclovir 500mg qd maintenance
- Lotemax tid for recurrence
Prodromal epithelial relapses
- Trifluridine qd maintenance
- Chronic epithelial toxicity & SPK
- Trifluridine bid for relapse
Trifluridine bid switched to Zirgan bid
20/40- improved to 20/25

78 yo African American male

Chronic myelogenous leukemia
WBC > 60,000
Acyclovir 400 bid preventive maintenance
Acute dendritic keratitis OS
Zirgan 5/day for 7 days
Zirgan tid topical maintenance
Intensive dry eye therapy

Herpetic Keratitis Disease: U.S.A.

Estimated 20,000 primary infections per year
Estimated 28,000 relapses per year
Herpetic keratitis infection is one of the leading cause of corneal transplants
Herpes Simplex Virus (HSV):
- HSV-type 1
- HSV-type 2
Herpes Zoster Virus (HZV or VZV)

Ocular Herpes

Eyelids
Epithelium
Stroma
Endothelium
Trabeculum
Iris Stromal Atrophy
Iris Sphincter
Vitritis & Retinitis
Papillitis

Zirgan 0.15% Ganciclovir ophthalmic gel

First approved in 1995: Track Record
5 gram tube with dropper: Convenience
Carbomer gel vehicle: Comfort
Viral Thymidine kinase specific: Non-toxic
pH = 7.45: Non-irritating
5/day acute Rx: Compliance
Room temperature stable: No refrigeration

Zirgan^™ 0.15% Ganciclovir ophthalmic gel

Treatment of acute superficial herpetic keratitis1,2
Replaces less effective or less well tolerated antivirals2
First approved in France 1995: tradename Virgan
Approved in Europe for over 10 years
Clinical trials, compared to acyclovir (ACV) 3% ointment
Not Double-masked: Ganciclovir gel vs acyclovir ointment
No clinical trials comparing Ganciclovir to trifluridine (TFT)
Polyfoil 5 gram tube, dropper fitting, carbomer gel vehicle
pH = 7.45 and Osmolality = 300 mOsmol

1. Trousdale MD, et al. Efficacy of BW759 (9-[[2-hydroxy-1(hydroxymethyl)ethoxy]methyl]guanine) against herpes simplex virus type 1 keratitis in rabbits. Current Eye Research 1984;3(8):1007–1015.
2. Shiota H, Naito T, Mimura Y. Anti-herpes simplex virus (HSV) effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in rabbit cornea. Current Eye Research 1987;6(1):241–245.

Ganciclovir Mechanism of Action

Penetrates cell infected with the virus
Phosphorylated within the cell to ganciclovir monophosphate by a viral thymidine-kinase
- Affinity for viral thymidine-kinase allows for specificity in its action
Activation continues due to several cell kinases leading to formulation of ganciclovir triphosphate, which:
- Inhibits viral DNA polymerase
- Incorporates into viral DNA
- Prevents replication by chain termination

Zirgan^™ Clinical Efficacy Results

Results from an open-label, randomized, controlled, multicenter clinical trial evaluating
ganciclovir ophthalmic gel 0.15% compared to acyclovir ophthalmic ointment 3% in patients with dendritic ulcers

	GCV 0.15% N=77	ACV 3% N=67
Clinical Resolution By Day 7	55 (77%)	48 (72%)

Zirgan^™ Clinical Efficacy Results

Results from 3 randomized, single-masked, controlled multicenter clinical trials evaluating
ganciclovir ophthalmic gel 0.15% compared to acyclovir ophthalmic ointment 3% patients with dendritic ulcers

	GCV 0.15% N=57	ACV 3% N=49
Clinical Resolution By Day 7	41 (72%)	34 (69%)

Ocular Clearing With Zirgan


Dendritic ulceration before treatment with Zirgan^™	Cornea after treatment with Zirgan

Summary of Differences: Zirgan^™ Compared to Viroptic^®
(trifluridine ophthalmic solution) 1%

	Zirgan	Trifluridine
Dosage Forms	5 gram tube	7.5 mL dropper bottle
Storage	Store at 15°C-25°C (59°F-77°F)	Store under refrigeration 2° to 8°C (36° to 46°F)
Warnings	For topical use only Patients should not wear contact lenses if they have signs or symptoms of herpetic keratitis or during the course of therapy with Zirgan	Recommended dosage of administration should not be exceeded. Continuous administration of trifluridine for periods exceeding 21 days should be avoided because of potential ocular toxicity