The Science of Latisse

The Science of LATISSE®

(bimatoprost ophthalmic solution) 0.03%

LATISSE® (bimatoprost ophthalmic solution) 0.03%

Indication: LATISSE® (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth, including length, thickness, and darkness.

Important Safety Information:

Contraindications: LATISSE® is contraindicated in patients with hypersensitivity to bimatoprost or any other ingredient in this product.

LATISSE® (bimatoprost ophthalmic solution) 0.03% Important Safety Information (cont’d)

Warnings and Precautions: In patients using LUMIGAN® (bimatoprost ophthalmic solution) 0.03% or other prostaglandin analogs for the treatment of elevated intraocular pressure (IOP), the concomitant use of LATISSE® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN® for IOP reduction should only use LATISSE® after consulting with their physician and should be monitored for changes to their intraocular pressure.

Increased iris pigmentation has occurred when the same formulation of bimatoprost ophthalmic solution (LUMIGAN®) was instilled directly onto the eye. Although iridal pigmentation was not reported in clinical studies with LATISSE®, patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent.

Bimatoprost has been reported to cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes.


Warnings and Precautions (cont’d): There is the potential for hair growth to occur in areas where LATISSE® solution comes in repeated contact with skin surfaces.

LATISSE® solution should be used with caution in patients with active intraocular inflammation (eg, uveitis) because the inflammation may be exacerbated.

LATISSE® contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to application of solution and may be reinserted 15 minutes following its administration.


Adverse Reactions: The most frequently reported adverse events were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and erythema of the eyelid. These events occurred in less than 4% of patients.

Dosage and Administration: Apply nightly directly to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying applicators. Blot any excess solution beyond the eyelid margin. Dispose of the applicator after one use. Repeat for the opposite eyelid margin using a new sterile applicator. Do not apply to the lower eyelash line.

Other Safety Information

Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution (LUMIGAN®) for elevated intraocular pressure (IOP). LATISSE® should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products.

Patients should also be informed of the possibility of disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth.

For more information on LATISSE®, please refer to full prescribing information.

http://www.allergan.com/assets/pdf/latisse_pi.pdf

LATISSE® (bimatoprost ophthalmic solution) 0.03%Is a Structural Prostaglandin Analog1

Precise mechanism of action is unknown

LATISSE® solution likely penetrates the hair follicle via the dermis– The physicochemical

properties of LATISSE® solution favor its effective skin absorption to the dermis where hair follicles reside

LATISSE® is believed to exert its effects by stimulating the prostamide receptor2,3

1. LATISSE® [package insert]. Irvine, CA: Allergan, Inc.; 2008; 2. Woodward DF et al. Pharm Ther. 2008;120:71-80; 3. Woodward DF et al. Br J Pharmacol. 2008;153:410-419.

Molecular Structure of LATISSE®

(bimatoprost ophthalmic solution) 0.03%

LATISSE® (bimatoprost ophthalmic solution) 0.03% Increases Overall Eyelash Prominence

Precise mechanism of action is unknown1

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;155:1170-1176; 5. Data on file. Allergan, Inc.

Stimulates transition from telogen to anagen5

Prolongs anagen1

Normal Eyelash Cycle2-4 Effect of LATISSE®

Percent of eyelashes in anagen1

Anagen≈ 1-2 months

Catagen≈ 15 days

Telogen≈ 4-9 months

Exogen

A Multicenter, Double-Masked, Randomized, Parallel Study Assessing the Safety and Efficacy

of Once-Daily Application of LATISSE® (bimatoprost ophthalmic solution) 0.03%

Compared With Vehicle in Increasing Overall Eyelash Prominence

INVESTIGATORS

Alastair Carruthers, MA, BM, BCh Richard G. Glogau, MD

Jean Carruthers, MD Derek H. Jones, MD

Joel L. Cohen, MD Gary P. Lask, MD

Sue Ellen Cox, MD Stacy Smith, MD

Doris J. Day, MD Wm. Philip Werschler, MD

Lisa Donofrio, MD David Wirta, MD

Steven Fagien, MD, FACS Jessica Wu, MD

Dee Anna Glaser, MD Steven Yoelin, MD

Study Design to Measure Efficacy and Safety

Randomized, multicenter, double-masked, vehicle-controlled trial

Daily treatment for 4 months with 1-month posttreatment follow-up

Primary efficacy measure– Global eyelash assessment (GEA) scale

Secondary efficacy measure– Digital image analysis

Safety measures– Adverse events (AEs)– Ocular—biomicroscopy, intraocular pressure (IOP), ophthalmoscopy

(dilated), and visual acuity– Nonocular—pulse rate, blood pressure (systolic/diastolic)

Please see Important Safety Information on slides 2-6.

Primary Efficacy Measure Was a Validated GEA Scale*

To determine GEA score (a measure of eyelash prominence), raters evaluated length, fullness, and color of both sets of upper eyelashes

Responders were defined as persons with at least a 1-grade improvement from baseline

Grade 1 – MinimalInclusion Criteria

Grade 2 – ModerateInclusion Criteria

Grade 3 – Marked Grade 4 – Very Marked

*Scale demonstrated reliability and reproducibility in a study of 68 subjects.

Data on file. Allergan, Inc.

Secondary Efficacy Measure Was Digital Image Analysis

Change from baseline to week 16 in:– Length measured in pixels within

the area of interest (AOI)

– Thickness measured in pixels within AOI

– Darkness measured as intensity

Standardized technology and methodology– Equipment and setting

– Alignment, position and lighting

– Image acquisition, calibration



Subjects Instructed on Proper Application of Study Medication

Apply one drop of bimatoprost solution to the single-use-per-eye applicator Brush applicator along upper eyelash margin Repeat for the opposite eyelid margin using a new sterile applicator Dab or blot any excess medication Apply to a clean face at night after all makeup is removed Do not insert contact lenses until ≥15 minutes after application Do not apply to the lower eyelash line Additional applications of bimatoprost solution will not increase the growth of eyelashes


LATISSE® (bimatoprost ophthalmic solution) 0.03% Applicators

Proper use of LATISSE® requires the accompanying FDA-approved sterile applicators1

The FDA-approved sterile applicators are designed to help patients properly apply the product

– Volume of bimatoprost when applied to the eyelid margin with the applicator is ≈ 5% of the volume used as an eyedrop2

Do not apply LATISSE® in the eye or to the lower lid1

DO NOT APPLY in your eye or to the lower lid because excess hair growth outside the treatment area may occur. ONLY use the sterile applicators supplied with LATISSE® to apply the product1

Do not allow the tip of the bottle or applicator to contact surrounding structures, fingers, or any other unintended surface in order to avoid contamination by common bacteria known to cause infections.1 There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products

LATISSE® contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to application of LATISSE® and may be reinserted 15 minutes following its administration1

It is possible for hair growth to occur in other areas of your skin that LATISSE® frequently touches. Any excess solution outside the upper eyelid margin should be blotted with a tissue or other absorbent material to reduce the chance of this from happening. It is also possible for a difference in eyelash length, thickness, fullness, pigmentation, number of eyelash hairs, and/or direction of eyelash1

1. . LATISSE® [package insert]. Irvine, CA: Allergan, Inc 2. Data on file. Allergan, Inc.


Direct Application to the Eyelid Margin Decreases Dose Volume

Dermal ApplicationEyedrop

Eyedrop Dermal Application

Volume of bimatoprost applied to the upper eyelid margin with the applicator is ~5% of the volume used as an eyedrop


Subject Disposition of the Pivotal Trial


(n=137)

Completed(n=131)

Completed(n=126)

Early Terminations

AE (n=4)Lack of efficacy (n=0)Lost to follow-up (n=3)Protocol violation (n=2)Personal reasons (n=4)

Other (n=2)

Early Terminations

AE (n=4)Lack of efficacy (n=0)Lost to follow-up (n=0)Protocol violation (n=0)Personal reasons (n=1)

Other (n=1)

Vehicle(n=141)

Enrolled/Randomized(n=278)

Screened(n=409)

Demographic Data: Well Matched Across Age Group

Characteristics


(n=137)Vehicle(n=141)

Age in years (mean) 49.9 49.7

<45 (%) 44 (32.1) 43 (30.5)

45-65 (%) 82 (59.9) 88 (62.4)

>65 (%) 11 (8.0) 10 (7.1)

Min, Max 22, 77 22, 78

Sex

Female (%) 134 (97.8) 136 (96.5)

Male (%) 3 (2.2) 5 (3.5)

Race

Caucasian (%)* 109 (79.6) 116 (82.3)

Black (%) 0 1 (0.7)

Asian (%) 18 (13.1) 16 (11.3)

Hispanic (%) 6 (4.4) 5 (3.5)

Other (%) 4 (2.9) 3 (2.1)

*Higher percentage of lighter-skinned subjects likely due to technicalities of protocol-inclusion criteria (imaging criteria and baseline GEA score).Data on file. Allergan, Inc.

LATISSE® (bimatoprost ophthalmic solution) 0.03% Significantly Increases Percentage of Subjects With 1-Grade Improvement

5.1%

14.6%

50.4%*

69.3%*

78.1%*

78.6%*

21.4%18.4%19.9%

14.9%

7.8%

2.1%

0

10

20

30

40

50

60

70

80

90

1 4 8 12 16 20

Differences noted as early as week 1. Last observation carried forward performed on weeks 1 to 16. *P<.0001.Percentage change reported above each data point.

GEA score 2 (moderate) at baseline

GEA score 3 (marked) at week 16

Week

Su

bje

cts

Wit

h a

t L

east

a 1

-Gra

de

Imp

rove

me

nt

in G

EA

Fro

m B

ase

lin

e (%

)

LATISSE® (N=137)

Vehicle (N=141)

LATISSE® Treated Subject

Individual results may vary. If discontinued, lashes will gradually return to their previous appearance.Patients should also be informed of the possibility of disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth.


LATISSE® (bimatoprost ophthalmic solution) 0.03% Significantly Improves Eyelash Length

*P=.001; †P<.0001.Error bars = 2 standard error (SE).Percentage change reported above each data point.

Mea

n C

han

ge

Fro

m B

asel

ine

(mm

)

Week1 4 8 12 16 20

†

†

†

†

*

-0.20

0.00

0.20

0.40

0.60

0.80

1.00

1.20

1.40

1.60

1.80

1.2% 1.4%2.3%1.2%

1.4%

1.4%0.3%

25.9%24.6%

20.6%

11.5%

4.2%

LATISSE® (N=137)

Vehicle (N=141)

LATISSE® treated subject representing mean change in length at week 16

Baseline


LATISSE® (bimatoprost ophthalmic solution) 0.03% Significantly Improves Eyelash Fullness/Thickness

*P<.0001.Error bars = 2 SE.Percentage change reported above each data point.

Week

Mea

n C

han

ge

Fro

m B

asel

ine

(mm

2 )

*

*

*

*

1 4 8 12 16 20-0.10

0.00

0.10

0.20

0.30

0.40

0.50

0.60

0.70

0.80

0.90

9.9%

18.8%

11.7%10.2%10.1%

9.4%5.1%

100.2%

106.0%

82.2%

34.6%

15.8%

LATISSE® (N=136)

Vehicle (N=140)

LATISSE® treated subject representing mean change in fullness/thickness at week 16

Baseline


LATISSE® (bimatoprost ophthalmic solution) 0.03% Significantly Improves Eyelash Darkness

*P<.05; †P<.0001.Error bars = 2 SE. Percentage change reported above each data point.

LATISSE® treated subject representing mean change in darkness at week 16

LATISSE® (N=137)

Vehicle (N=141)

Mea

n C

han

ge

Fro

m B

asel

ine

(un

its)

Week

*

†

††

†

Imp

rove

me

nt

Imp

rove

me

nt

-25

-20

-15

-10

-5

0

51 4 8 12 16 20

2.5% 3.0%3.6%

1.9%2.4%

4.9%

0.9%

18.0%18.2%

15.1%

8.1%

4.3%

Baseline


Incidence of AEs

Number of Subjects (%)

Most Frequently Reported Adverse Events

LATISSE® (n=137)

Vehicle (n=141)

Eye pruritus 5 (3.6) 1 (0.7)

Conjunctival hyperemia* 5 (3.6)† 0 (0.0)

Skin hyperpigmentation 4 (2.9) 1 (0.7)

Eye irritation 3 (2.2) 2 (1.4)

Dry eye 3 (2.2) 1 (0.7)

Erythema of eyelid 3 (2.2) 1 (0.7)

*P<.05 vs vehicle; †All cases of conjunctival hyperemia were fully resolved by the end of the study.

Fewer than 4% of patients experienced treatment-related adverse events


Iris Pigmentation

Increased iris pigmentation has occurred when the same formulation of bimatoprost ophthalmic solution (LUMIGAN®) was instilled directly into the eye. Although iridal pigmentation was not reported in clinical studies with LATISSE® (bimatoprost ophthalmic solution) 0.03%, patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent1

No patients (0%) experienced iris pigmentation changes (dermal application)

Lack of iris pigmentation change in the LATISSE® trials likely due to upper eyelid margin application2

1. LATISSE® [package insert]. Irvine, CA: Allergan, Inc.; 2008; 2. Data on file. Allergan, Inc.

Effects on Ocular Safety

The reduction in IOP was not cause for clinical concern– Mean IOP:

Baseline: 14.5 mm Hg both groupsWeek 16: 13.7 mm Hg vehicle, 13.3 mm Hg bimatoprost

– Small, statistically significant between-group differences during the study

All less than 1 mm Hg and not clinically relevant

– Average of subjects’ range of IOPs (maximum to minimum IOP) during study (baseline to week 16) was 3.7 mm Hg for vehicle and 3.9 mm Hg for LATISSE® (bimatoprost ophthalmic solution) 0.03%

Pivotal Trial Summary: LATISSE® (bimatoprost ophthalmic solution) 0.03% Significantly Improves Eyelash Length, Thickness, and Darkness

LATISSE® solution significantly improved eyelash prominence, length, thickness, and darkness of eyelashes compared with vehicle– The majority of subjects began to experience significant results by week 8

with full results in 12 to 16 weeks

LATISSE® solution was well tolerated when applied to the upper eyelid margins of healthy adults daily for 4 months


Perspectives on the Role of LATISSE® (bimatoprost ophthalmic solution) 0.03% as a Potential Catalyst for Your Practice

A Market Category in Medical Aesthetics

LATISSE® (bimatoprost ophthalmic solution) 0.03%: Could Be a Catalyst for Medical Aesthetics

1. 2009 – MWB Monthly DTC Tracker = Among MD Rx considerers, those considering facial injectables in the next 2 years = 54%; 2. Data on file. BCG/Harris Consumer Quantitative Conjoint Research; Allergan, Inc., 2008; 3. Data on file. Kaiser Associates BEG MD Survey; Allergan, Inc., 2008; 4. Consumer A&U 06/09, n=192; 5. MD A&U 06/09, n=203.

More potential patients.

More potential procedures.

LATISSE® has the potential to TRIPLE the aesthetic market


1. Data on file. Allergan, Inc. 2008. BCG Harris Consumer Quantitative Conjoint Research; 2. Data on file. LATISSE® MD A&U Q2-09 Report, July 13, 2009, Allergan, Inc.; 3, Data on file. LATISSE® Consumer A&U Q2-09 Report, July 13, 2009, Allergan, Inc.; 4. Data on file. LATISSE® Value Proposition, September 2009, Allergan, Inc.

LATISSE® (bimatoprost ophthalmic solution) 0.03% Could Be a Catalyst for Medical Aesthetics

Existing patients5 million existing aesthetic patients place

importance on their lashes1

75% of LATISSE® users are existing patients in an MD office (n=273)2

24% of LATISSE® users are already first-time buyers of other treatments* from same MD (n=192)3

New patients 80% are receptive to hearing about

LATISSE® (n=199)2

25% of MDs report that LATISSE® has driven new patients into the practice (n=294)2

MDs report ~23% of LATISSE® new patients are cross-sold* (n=203)2

New and existing patients Of these patients, 87% of LATISSE® users already told friends and family (n=189)3

In an analysis of 576 patients coming in for LATISSE®, 64% of new and existing patients received additional products and services (n=576)4

*IIncludes facial injectables and skin care products.

Market Research Shows

Not all consumers are potential LATISSE® patients. Only a physician can determine who is an appropriate patient.

LATISSE® (bimatoprost ophthalmic solution) 0.03%Advertising

Massive consumer campaign to help drive patient demand:

– Consumer marketing campaigns developed by Allergan have the potential to create demand and attract new patients:

Advertising and PR: National exposure across TV, magazines, and the Internet

Find a Doctor tool: Links consumers to Allergan physician customers

Over 1 billion impressions anticipated

– Brooke, known for her eyes adds instant brand awareness and recall for LATISSE®, which may mean your patients will ask for LATISSE® by name!


LATISSE® (bimatoprost ophthalmic solution) 0.03%: Practice Analysis Objective and Methodology

Objective

To support market research findings that patients using LATISSE®

present an opportunity to expand the aesthetic marketplace

Methodology

39 participating accounts in dispensing and nondispensing states

Plastic surgeons, dermatologists, and other

576 LATISSE® patient consults occurred, which included new and existing patients

Consult requests for LATISSE® only (demand)

Data on additional products or services purchased during the consult were captured in the study

Of the 576 patients, 78 patients were in Rx-only states

97% of patients who came in for LATISSE® either bought LATISSE® or received a prescription for LATISSE®

– 87% purchased LATISSE®

– 13% received a prescription

64% or 370 patients coming in for LATISSE® purchased an additional product or service other than LATISSE®

– 46% facial injectables– 28% skin care products– 27% skin care services, including laser– 4% surgery

LATISSE® (bimatoprost ophthalmic solution) 0.03% as a Catalyst: 16-Week Data

576 Patients – 39 Practices

Data on file. LATISSE® Value Proposition, September 2009, Allergan, Inc.

LATISSE® (bimatoprost ophthalmic solution) 0.03%: Increasing the Growth of Eyelashes

LATISSE® is the first and only treatment approved by the FDA indicated to treat hypotrichosis* of the eyelashes by increasing their growth including length, thickness, and darkness

*Hypotrichosis is another name for having inadequate or not enough eyelashes.FDA=US Food and Drug Administration.

LATISSE® [package insert]. Irvine, CA: Allergan, Inc.


Indication: LATISSE® (bimatoprost ophthalmic solution) 0.03% is indicated to treat hypotrichosis of the eyelashes by increasing their growth, including length, thickness, and darkness.

Important Safety Information:

Contraindications: LATISSE® is contraindicated in patients with hypersensitivity to bimatoprost or any other ingredient in this product.


Warnings and Precautions: In patients using LUMIGAN® (bimatoprost ophthalmic solution) 0.03% or other prostaglandin analogs for the treatment of elevated intraocular pressure (IOP), the concomitant use of LATISSE® may interfere with the desired reduction in IOP. Patients using prostaglandin analogs including LUMIGAN® for IOP reduction should only use LATISSE® after consulting with their physician and should be monitored for changes to their intraocular pressure.

Increased iris pigmentation has occurred when the same formulation of bimatoprost ophthalmic solution (LUMIGAN®) was instilled directly onto the eye. Although iridal pigmentation was not reported in clinical studies with LATISSE®, patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent.

Bimatoprost has been reported to cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes.


Warnings and Precautions (cont’d): There is the potential for hair growth to occur in areas where LATISSE® solution comes in repeated contact with skin surfaces.

LATISSE® solution should be used with caution in patients with active intraocular inflammation (eg, uveitis) because the inflammation may be exacerbated.

LATISSE® contains benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to application of solution and may be reinserted 15 minutes following its administration.


Adverse Reactions: The most frequently reported adverse events were eye pruritus, conjunctival hyperemia, skin hyperpigmentation, ocular irritation, dry eye symptoms, and erythema of the eyelid. These events occurred in less than 4% of patients.

Dosage and Administration: Apply nightly directly to the skin of the upper eyelid margin at the base of the eyelashes using the accompanying applicators. Blot any excess solution beyond the eyelid margin. Dispose of the applicator after one use. Repeat for the opposite eyelid margin using a new sterile applicator. Do not apply to the lower eyelash line.

Other Safety Information

Macular edema, including cystoid macular edema, has been reported during treatment with bimatoprost ophthalmic solution (LUMIGAN®) for elevated intraocular pressure (IOP). LATISSE® should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular edema.

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products.

Patients should also be informed of the possibility of disparity between eyes in length, thickness, pigmentation, number of eyelashes or vellus hairs, and/or direction of eyelash growth.

For more information on LATISSE®, please refer to full prescribing information.

©2010 Allergan, Inc. ® and ™ marks owned by Allergan, Inc.APC87SE10

http://www.allergan.com/assets/pdf/latisse_pi.pdf

The Science of Latisse

Health & Medicine

Transcript of The Science of Latisse