1

Timothy L. Comstock, ODOliver D. Schein, MD

Tuyen Ong, MDKaren Kesler, PhD

Disclosures: T Comstock and T Ong are employees of Bausch & Lomb, Inc. O Schein is a consutlant for Bausch & Lomb, Inc. Karen Kesler is an employee of Rho, Inc. which conducted the statistical analysis.

Safety and Efficacy of Mapracorat Ophthalmic Safety and Efficacy of Mapracorat Ophthalmic Suspension in the Treatment of Inflammation Following Suspension in the Treatment of Inflammation Following

Cataract Surgery: Adaptive Design StudyCataract Surgery: Adaptive Design Study

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• To identify the most effective drug concentration and dose frequency of mapracorat (BOL-303242-X), a novel selective glucocorticoid receptor agonist (SEGRA), for the treatment of inflammation following uncomplicated cataract surgery.

PurposePurpose

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• Phase II, multicenter, randomized, double-masked, parallel-group, vehicle-controlled, dose ranging study.

• Subjects were aged ≥18 years with postoperative anterior chamber (AC) cells of ≥Grade 2 (6-15 cells) on the day following uncomplicated cataract surgery.

• Subjects expecting to require concurrent ocular therapy with topical NSAIDs, mast cell stabilizers, antihistamines, or decongestants, or systemic NSAIDs or systemic/ocular corticosteroids were excluded.

MethodsMethods

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• Eligible subjects self-administered 1-2 drops of study treatment (mapracorat 1%, 2%, 3% or vehicle) QD, BID, or QID for 14 days and completed 7 visits.

MethodsMethods

Visit 1 [Screening](≤14 days prior to surgery)

• Eligibility assessment• Clinical assessment of

ocular symptoms• Eye examination (VA,

IOP, biomicroscopy, fundoscopy)

• AEs & concomitant medications

Visit 2 [Surgery]• AEs & concomitant

medications

Visit 3 [Post-op Day 1]• Clinical assessment of

ocular symptoms• Eye examination (VA, IOP,

biomicroscopy)• AEs & concomitant

medications• Determination of

eligibilityVisit 4 [Day 3 ±1] • Clinical assessment of

ocular symptoms• Eye examination (VA, IOP,

biomicroscopy)• AEs & concomitant

medications

Visit 5 [Day 8 ±1] • Clinical assessment of

ocular symptoms• Eye examination (VA, IOP,

biomicroscopy)• AEs & concomitant

medications

• Visit 6 [Day 15 ±1] • Clinical assessment of

ocular symptoms• Eye examination (VA,

IOP, biomicroscopy, fundoscopy)

• AEs & concomitant medications

• Visit 7 [Day 18 ±1] • Clinical assessment of

ocular symptoms• Eye examination (VA, IOP,

biomicroscopy)• AEs and concomitant

medications

Mapracorat

Vehicle

5

• Primary efficacy endpoint: – Proportion of subjects with complete resolution of AC

cells at visit 5 (postoperative day 8)

• Secondary efficacy endpoints: – Proportion of subjects with Grade 0 pain at visit 5 and at

each visit– Resolution of AC cells, AC flare and overall AC

inflammation at each visit

• Safety endpoints: – Incidence of ocular and non-ocular adverse events (AEs)– Change from baseline in intraocular pressure (IOP),

visual acuity (VA), and biomicroscopy and ophthalmoscopy findings

MethodsMethods

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Results: SubjectsResults: Subjects

Subject Demographics-ITT population

Mapracorat Vehicle

1% 2% 3% QD, BID, QIDFrequency BID QD BID QID QD BID QID

N (%) 60 (14) 28 (7) 28(7) 60 (14) 59 (14) 60 (14) 60 (14) 60 (14)

Age, yr

Mean (SD) 65.4 (12.0) 67.9 (10.9) 68.9 (10.5) 69.5 (7.1) 68.2 (10.8) 67.3 (10.7) 68.5 (10.3) 67.1 (10.8) Median 66.5 68.5 70.0 69.0 70.0 66.5 70.0 67.5 Min, max 28, 89 32, 85 42, 87 57, 83 22, 84 44, 90 44, 87 43, 87

Gender, N(%)

Male 27 (45.0) 13 (46.4) 13 (46.4) 26 (43.4) 29 (49.2) 28 (46.7) 29 (48.3) 28 (46.7) Female 33 (55.0) 15 (53.6) 15 (53.6) 34 (56.7) 30 (50.8) 32 (53.3) 31 (51.7) 32 (53.3)

Race, N(%)

Asian 1 (1.7) 0 0 1 (1.7) 3 (5.1) 0 2 (3.3) 0 Black 5 (8.3) 3 (10.7) 1 (3.6) 2 (3.3) 4 (6.8) 3 (5.0) 3 (5.0) 4 (6.7) White 53 (88.3) 25 (89.3) 27 (96.4) 55 (91.7) 52 (88.1) 57 (95.0) 55 (91.7) 55 (91.7) Other 1 (1.7) 0 0 2 (3.3) 0 0 0 1 (1.7)

• 415 subjects were randomized and included in the ITT population• Subjects ranged in age from 22 to 90 years with a mean (SD) age of 67.8

(10.4) years. • The median ages and proportion of male and female subjects were similar for

all treatment groups

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Results: Complete Resolution of AC Cells at Visit 5 Results: Complete Resolution of AC Cells at Visit 5 (postoperative day 8)—Primary Efficacy Endpoint(postoperative day 8)—Primary Efficacy Endpoint

21.7 21.4

14.3

28.3

25.4 25

30

5

0

5

10

15

20

25

30

35

1% B

ID

2% Q

D

2% B

ID

2% Q

ID

3% Q

D

3% B

ID

3% Q

ID

Vehic

le

% S

ub

jec

ts w

ith

co

mp

lete

Re

so

luti

on

• The mapracorat 2% QID and all 3% dose frequencies were highly significantly better than vehicle for resolution of AC cells (28.3%, 25.4%, 25.0% and 30.0%, respectively vs. 5% for vehicle).

†

*P<0.05, †P<0.0005

* *† †

†

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Results: Grade 0 Pain at Visit 5 (postoperative day 8)Results: Grade 0 Pain at Visit 5 (postoperative day 8)

58.3

67.9

53.6

78.3

71.275

70

50

0

10

20

30

40

50

60

70

80

1% B

ID

2% Q

D

2% B

ID

2% Q

ID

3% Q

D

3% B

ID

3% Q

ID

Vehic

le

% S

ub

jec

ts w

ith

Gra

de

0 P

ain

• The mapracorat 2% QID and all 3% dose frequencies were significantly better than vehicle for pain resolution (78.3%, 71.2%, 75.0% and 70.0%, respectively vs. 50% for vehicle).

**

**

*P<0.05

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Serious Adverse Events (SAEs)• No non-ocular SAEs• 2 treatment-emergent ocular SAEs

– Cystoid macular edema (CME; 3% QD group, possibly related to the study group and probably related to study procedure)

– Subretinal neovascularization (3% BID group, unrelated to the study drug or study procedure)

Treatment-Emergent and Related Non-Ocular AE’s• 3 events total

– Rash (Vehicle group)– Headache (2% QID group) – Nausea –(3% QD group)

Results: Adverse EventsResults: Adverse Events

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Results: Adverse EventsResults: Adverse Events

Ocular Treatment Emergent AEs Related to Study Drug Occuring in >3% of Eyes in Any Treatment Group*

Mapracorat Vehicle

1% 2% 3% QD, BID, QID

(N=60)Dose Frequency

BID

(N=60)

QD

(N=28)

BID

(N=28)

QID

(N=60)

QD

(N=59)

BID

(N=60)

QID

(N=60)

Total No of AEs* 16 1 4 6 9 9 7 23

No of subjects with ≥ 1 AE 10 (16.7) 1 (3.6) 3 (10.7) 3 (5.0) 8 (13.6) 9 (15.0) 6 (10.0) 12 (20.0)

AC Inflammation 1 (1.7) 0 0 1 (1.7) 1 (1.7) 0 2 (3.3) 3 (5.0)

Eye Pain 2 (3.3) 0 1 (3.6) 0 0 1 (1.7) 0 4 (6.7)

Photophobia 2 (3.3) 0 0 1 (1.7) 0 0 1 (1.7) 3 (5.0)

Eye Pruritis 2 (3.3) 1 (3.6) 0 0 1 (1.7) 1 (1.7) 0 0

AC Flare 0 0 1 (3.6) 0 0 0 0 3 (5.0)

Conjunctival Hyperemia 0 0 1 (3.6) 0 1 (1.7) 0 0 1 (1.7)

Dry Eye 2 (3.3) 0 0 0 0 1 (1.7) 0 0

Eye Irritation 0 0 1 (3.6) 0 1 (1.7) 0 1 (1.7) 0

Ocular Hyperemia 1 (1.7) 0 0 0 0 0 0 2 (3.3)

Eye Inflammation 0 0 0 0 0 2 (3.3) 0 0*prior to rescue medication use

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Results: Mean IOP for Each Visit, Safety PopulationResults: Mean IOP for Each Visit, Safety Population

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12

14

16

18

20

1% BID (n=60)

2% QD (n=28)

2% BID (n=28)

2% QID (n=60)

3% QD (n=59)

3% BID (n=60)

3% QID (n=60)

Vehicle (n=60)

Me

an

IO

P (

mm

Hg

)

• Mean IOP did not change from baseline for any treatment.• Four reports of increased IOP ≥10 mm Hg (1 vehicle, 2

mapracorat 1% BID, 1 mapracorat 3% BID) were not dose related and none exceeded 30 mm Hg.

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• Mapracorat 2% QID treatment and all 3% dose frequencies (QD, BID, QID) demonstrated statistically significant improvements in both AC cells and Grade 0 pain at visit 5 (postoperative day 8) compared with vehicle.

• Results for secondary endpoints, including results at visit 6 (day 15) and visit 7 (day 18), were consistent with primary outcomes (data not shown)

• Treatment related adverse effects were infrequent in all treatment groups

• IOP effects were similar to vehicle.

Conclusions Conclusions