1. Steven G. Yoelin, MD, John G. Walt, MBA
Safety, Effectiveness, and Subjective Experience With Topical Bimatoprost 0.03% for Eyelash Growth
Steven G. Yoelin, MD, John G. Walt, MBA
Financial disclosures:
Steven G. Yoelin, MD, received an unrestricted research grant from Allergan, Inc. to support the study.
John G. Walt is Health Outcomes Researcher at Allergan, Inc.

2. Background: Eyelash Functions
Eyelashes help protect the eye from debris and excessive sunlight
Eyelash prominence has been described as having a positive psychological effect1,2
Prominent eyelashes are widely considered to be a desirable physical attribute1,2
Eyelash prominence is defined by length, fullness (thickness), and darkness (intensity) based on a validated measure3
Core deck slide 3
1. Holló G. Expert Opin Drug Saf. 2007;6:45-52; 2. Batchelor D. Eur J Cancer Care (Engl). 2001;10: , 3. Yoelin S et al. Poster presented at: 33rd Hawaii Dermatology Seminar; February 7-13, 2009; Wailea, Hawaii.
[Khong 2006, p ] [Shaikh 2006, p76] [BEG PI, p2] [Adler’s 1970, p 1] 2

3. Background: Bimatoprost Ophthalmic Solution 0.03% for Eyelash Growth
Bimatoprost is a structural prostaglandin analog1
Prostaglandins act as local regulators that mediate a variety of physiological functions, including vasoconstriction/vasodilation, platelet aggregation, and bronchoconstriction/ bronchodilation2
Bimatoprost likely penetrates the hair follicle via the dermis
Physicochemical properties favor its effective skin absorption to the dermis where hair follicles reside
Eyelid-margin application delivers approximately 5% of the applied dose compared with an eyedrop3
Long-term safety profile of bimatoprost ophthalmic solution 0.03% has been established since its approval in the United States (March 2001) for the treatment of elevated intraocular pressure/ocular hypertension4-6
Molecular Structure of Bimatoprost
Core deck slide 14,
Kurstjens deck slides 3-4
1. LATISSE™ [package insert]. Irvine, CA: Allergan, Inc.; 2008; 2. Smyth EN et al. In: Brunton LL et al, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 11th ed. New York, NY; McGraw-Hill Companies, Inc: 2006; 3. Data on file. Allergan Inc.; 4. Higginbotham EJ et al. Arch Ophthalmol. 2002;120: ; 5. Cohen JS et al. Surv Ophthalmol. 2004;49:S45-S52; 6. Williams RD et al. Br J Ophthalmol. 2008;92:
[Brubaker # p23-24]
[Higgenbotham # p ]
[Cohen 2003 p62]
[Brandt # p1030]
[Williams 2008, p 1387]
[Data on File, Allergan Inc]
[Whitcup 2003] 3

4. Background: Mechanism of Action Hypothesis
Increases the percent of eyelashes in anagen1
Normal Eyelash Cycle2-4
Effect of Bimatoprost Ophthalmic Solution 0.03%
~5 months (4-9 months)
Stimulates transition from telogen to anagen5
~15 days
Core deck slide 18
Prolongs anagen5
~1-2 months
1. LATISSE™ [package insert]. Irvine, CA: Allergan, Inc.; 2008; 2. Johnstone MA, Albert DM. Surv Ophthalmol. 2002;47(suppl 1):S185-S202; 3. Elder MJ. Ophthal Plast Reconstr Surg. 1997;13:21-25; 4. Na JI et al. Br J Derm. 2006;155: ; 5. Data on file. Allergan Inc.

5. Objective
To investigate the safety, efficacy and subjective experience of bimatoprost ophthalmic solution 0.03% for the treatment of hypotrichosis*
*Hypotrichosis is another name for having inadequate or not enough eyelashes.

6. Methods: Study Design
A prospective, open-label study of healthy female subjects who desired longer, thicker (fuller), and darker natural eyelashes
Subjects were at least 18 years old, and had an intraocular pressure (IOP) no higher than 22 mm Hg
Subjects were instructed to apply bimatoprost ophthalmic solution 0.03% bilaterally to the upper eyelid margin once daily for 12 weeks
Subjects were instructed to wipe the areas immediately around the eyelid afterward to remove excess medication
Safety measures
Adverse events (AEs)
Visual acuity
IOP
Biomicroscopy
Periorbital darkening
Efficacy measure
Patient satisfaction questionnaire
[CSR p.2 para. 3 Study Methodology]
[CSR p.2 para. 5 Study Methodology]
[CSR p 3, ]
[CSR p 27, 34, 48, 23, 31, 39 – in order of bullets]
[Protocol #032: p21, 36-37, 43, 70-83] 6

7. Results: Patient Demographics
Enrolled population: 28 subjects
100% female
96% Caucasian
Average age of 49 years (range: 32 to 73)
In good health
22 subjects completed the study
CSR p 5]
[ MA001 Study Summary (June 12).doc p5]

8. Results: Subject Reported Eyelash Improvement and Onset of Action
Subject-Reported Effectiveness at Week 12
Subject-Reported Onset of Improvement
Subjects Responding (%)
Subjects Responding (%)
CSR p 10
Change in Eyelashes From Baseline
Time of Onset
[ MA001 Study Summary (June 12).doc p5, 10]

9. Results: Representative Eyelash Effects with Bimatoprost Ophthalmic Solution 0.03%
Pretreatment
Bimatoprost 0.03%
Photographs courtesy of Steve Yoelin, MD.

10. Results: Patient Satisfaction
Within 3 months
All subjects (16/16) indicated that their eyelashes were “improved” or “much improved” compared to before treatment
Most subjects (94%; 15/16) “much” or “very much” agreed that bimatoprost ophthalmic solution 0.03% was helpful and that they had done something positive for their appearance (75%; 12/16)
All subjects agreed that they felt more attractive at the end of the treatment period

11. Results: Bimatoprost Ophthalmic Solution 0
Results: Bimatoprost Ophthalmic Solution 0.03% Was Generally Well Tolerated
Common AEs reported: eye redness, pigmentation changes or redness, mild itchiness, burning, eye dryness
No AEs resulted in study discontinuation
No serious or unexpected AEs were reported
Skin darkening in the general application area was noted at least once for 5 subjects
For 4 subjects: noted as “possible,” “slight,” “small,” or “a little”
For 1 subject: noted as “yes”
Hyperemia not observed on biomicroscopy at any visit
No AEs related to visual acuity or IOP
Mean changes from baseline <1 mm Hg at any time point, indicating no clinical significance
CSR p 6
[ MA001 Study Summary (June 12).doc 10]

12. Conclusions
Bimatoprost ophthalmic solution 0.03% increased growth of natural eyelashes
The increased growth correlated with increased patient satisfaction
Bimatoprost ophthalmic solution 0.03% was generally well tolerated
Bimatoprost ophthalmic solution 0.03% is the first and only treatment approved by the US Food and Drug Administration indicated to treat hypotrichosis of the eyelashes by increasing their growth including length, thickness, and darkness