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Mitra Sehi, OD, PhD, MBA, FAAO
Director, Anterior Segment MSLs, Ophthalmology
ALLERGAN, PLC
BIMATOPROST SR: DISRUPTING THE GLAUCOMA TREATMENT PARADIGM
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GLAUCOMA PORTFOLIO will expand to provide more options to doctors and patients
2
Drops Portfolio
SustainedRelease
Surgical Devices
Disease Severity
Options to intervene at different stages
Ocular Hypertension
Early Moderate Severe
Bimatoprost Ocular RingBIMATOPROST SR
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Similar to those used in biodegradable sutures
Supplied preloaded in a single-use applicator
with a 28-gauge needle
Bimatoprost SR
Bimatoprost SR
Biodegradable Polymers
NOVADUR® platform
First-in-class sustained-release, biodegradable implant for the treatment of open-angle glaucoma or
ocular hypertension designed to lower IOP for at least 4 months, while freeing patients from daily
eyedrop regimens
Bimatoprost
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Bimatoprost SR Administration Procedure
Do not distribute, copy or publishCraven et al. AAO 2019
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• In vivo dog study
‒ Drug is detectable in the eye for up to 4 months after BimSR administration
‒ Targeted drug delivery to relevant sites of action of PGAs
Reprinted from Seal JR, et al, J Ocul Pharmacol Ther. 2019;35:50–57 and used under the terms of the Creative Commons License (http://creativecommons.org/licenses/by/4.0)
Seal et al. J Ocul Pharmacol Ther. 2019;35:50-57.
NondetectableNondetectable Nondetectable Nondetectable
Targeted Drug Delivery to the Relevant Site of Action of PGAs
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Ph
ase
2 S
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y R
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May Decrease Common Side Effects of Chronic Topical PGA Use
Walters, et al. ASCRS 2018.
Bim SR = Bimatoprost sustained-release implant*Patients counted only once within each preferred term and system organ class
Visible difference in common effects of chronic use of topical PGA
medication: Growth of eyelashes
Preferred Term* n (%)
Onset after 2 days of administration
Bim SR(N=75)
Bim 0.03%(n=75)
Conjunctival Hyperemia 13 (17.3) 21 (28.0)
Blepharitis 1 (1.3) 1 (1.3)
Erythema of eyelid 1 (1.3) 4 (5.3)
Eyelid edema 1 (1.3) 2 (2.7)
Growth of eyelashes 0 5 (6.7)
Iris hyperpigmentation 0 3 (4.0)
Conjunctival edema 0 1 (1.3)
Orbit atrophy 0 1 (1.3)
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Ph
ase
3 T
op
line
Positive Phase 3 Studies Topline Data
June 13, 2018 and January 7, 2019Do not distribute, copy or publish
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ARTEMIS Phase 3 Study Design
*Phone call. †Two Bimatoprost SR treatment groups, administered either 10-µg or 15-µg implant. Only results for the proposed marketed dose strength, Bimatoprost SR 10 µg, will be presented.
BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; BL, baseline; IOP, intraocular pressure.
Two Parallel-Group, Noninferiority Studies vs BID Timolol
Safety follow-up visits
SR treatment in study eye,
sham treatment and timolol BID
in fellow eye
No SR or sham treatment
Sham treatment in both eyes,
timolol BID in both eyes
• Primary efficacy endpoint: Noninferiority to timolol during primary efficacy period through
Week 12
Timolol BID
Week
BL 2 6 12 16 32 52
Month 20
Bimatoprost SR†
Primary efficacy period
Exit
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su
lts
Baseline Characteristics of Patients and Study Eyes
Parameter
Bimatoprost SR 10 µg(N=374)
Timolol 0.5% BID(N=374)
Age, mean (SD), y 62.6 (12.1) 62.0 (11.7)
Range 23–88 19–90
Male, n (%) 198 (52.9) 180 (48.1)
Race/ethnicity, n (%)
White 238 (63.6) 234 (62.6)
Black or African-American 51 (13.6) 57 (15.2)
Hispanic 45 (12.0) 46 (12.3)
Other or not reported 40 (10.7) 37 (9.9)
Diagnosis
OHT 76 (20.3) 86 (23.0)
POAG 290 (77.5) 277 (74.1)
Pseudoexfoliation or pigmentary glaucoma 8 (2.1) 11 (4.0)
Hour 0 (8 AM) IOP, mean (SD), mm Hg 24.5 (2.6) 24.6 (2.6)
Hour 2 (10 AM) IOP, mean (SD), mm Hg 23.3 (2.9) 23.3 (3.0)
Phakic lens status, n (%) 287 (76.7) 279 (74.6)
CECD, mean (SD), cells/mm2 2455 (328) 2462 (329)
Range 1540-3396 1423-3643
Pooled study data, ARTEMIS 1 + ARTEMIS 2
BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; CECD, central corneal endothelial cell density;
IOP, intraocular pressure; POAG, primary open-angle glaucoma; OHT, ocular hypertension. Do not distribute, copy or publish
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Bimatoprost SR Met the Primary Endpoint of Noninferiority to Timolol BID in IOP Lowering Through Week 12*
*Both 10 µg and 15 µg doses met the primary endpoint. Upper limit of 95% confidence interval of Bimatoprost SR − timolol difference was <1 mm Hg at Hours 0 and 2 at Weeks 2, 6, and 12 in each study, as well as in the pooled study dataset.
BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; IOP, intraocular pressure; W, weeks.
Primary Efficacy Results:
Mean IOP
• Mean diurnal IOP consistently
maintained between 16–17
mm Hg
• During the primary efficacy
period, IOP lowering was
numerically greater with
Bimatoprost SR than timolol at
all 6 time points
Pooled study data, ARTEMIS 1 + ARTEMIS 2
Error bars indicate the standard deviation.
10
14
18
22
26M
ean
Diu
rna
l IO
P (
mm
Hg
)
Time
Bimatoprost SR 10 µg (N=374)
BL 2W 6W 12W
Administration #1
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Co
mp
aris
on
of
Ph
ase
1/2
an
d P
has
e 3
Study Design and Primary Outcome
> 20-month Phase 3 study: OAG/OHT patients
(n=1122) were randomized to study eye
treatment with 3 administrations of Bimatoprost
SR 10 or 15 µg (Day 1; Weeks 16, 32) or topical
timolol 0.5% BID
> Primary endpoint: IOP lowering through
Week 12
Phase 3
> 2-year Phase 1/2 study: 75 OAG patients
received Bimatoprost SR 6, 10, 15 or 20 µg in
study eye, topical bimatoprost 0.03% QD in
fellow eye
> Interim analysis: Week 16
A P O L L
Phase 1/2
Week 2 through Week 16, 10 µg (n=21)
from a baseline of 24.5 mm Hg (Hour 0)
Week 2 through Week 12, 10 µg (n=374)
from a baseline of 24.5 mm Hg (Hour 0)
Up to
-7.7mm Hg
Up to
32%reduction from
baseline
Up to
-7.9 mm Hg
Up to
32%reduction from
baseline
BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; IOP, intraocular pressure; OAG, open-angle glaucoma; OHT, ocular hypertension; QD, once daily. Do not distribute, copy or publish
Results
No. of patients
at risk
Days
IOP
Su
rviv
al
Pro
ba
bil
ity
(no
re
tre
atm
en
t o
r re
scu
e)
1.0
0.8
0.6
0.4
0.2
0.0
0280
42
232
42
186
29
141
19
121
14
0
13 11 7
90 180 270 360 480 600 720
12W 26W 39W 52W 16M 20M 24M
Time After Last Administration
Bimatoprost SR, bimatoprost sustained-release implant; IOP, intraocular pressure; M, months; W, weeks.
Patients had Continued Duration of IOP Control With No Additional Treatment After Bimatoprost Release From Implant
Last Bimatoprost SR administration
80% IOP controlled with NO additional treatment at 1 year after 3 administrations of Bimatoprost SR 10 µg
Study #1 & #2
36%
1 Year
IOP controlled with NO additional treatment at 1 year after 1 administration of Bimatoprost SR 10 or 15 µg
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Topical Bimatoprost
Image on left used with permission of ARVO, from Morphological Changes in the Anterior Eye Segment after Long-Term Treatment with Different Receptor Selective Prostaglandin Agonists and a Prostamide, Richter et al,
Invest Ophthalmol Vis Sci. 44(10) 2003; permission conveyed through Copyright Clearance Center, Inc.
Monkey ciliary body after 1 year of topical
bimatoprost treatment
Remodeling enhances uveoscleral outflow
Bimatoprost SR: Proposed MOA*
Higher MMP expression, reduction in the ECM, may
lead to greater tissue remodeling, longer duration
of IOP reduction
*Artist’s rendition
Bimatoprost SR, bimatoprost sustained-release implant; ECM, extracellular matrix; IOP, intraocular pressure; MOA, mechanism of action; MMP, matrix metalloproteinase.
Rationale for Extended Duration of IOP Control
Pro
posed M
OA
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Significant Difference in Rate of Visual Field Progression Compared With Timolol in OAG Patients
Pooled study data, ARTEMIS 1 + ARTEMIS 2
• At planned primary database lock, 293 OAG patients in the Bimatoprost SR 10 µg and Timolol BID groups had available 1-year visual field data
*P = 0.049 vs timolol BID
MD values from Humphrey perimetry 24-2 full threshold or Swedish Interactive Threshold Algorithm (SITA) standard tests. Data after any use of rescue medication were excluded.
BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; MD, mean deviation; OAG, open-angle glaucoma.
*
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All Ocular Treatment-Emergent Adverse Events Reported in ≥3% of Study Eyes in Either Treatment Group
Onset at Any Time Onset or Worsening >2 Days After Implant/Sham Administration
Adverse Event, n (%)BimSR 10 µg
(N=372)Timolol BID
(N=370)BimSR 10 µg
(N=372)Timolol BID
(N=370)
Any adverse event 233 (62.6) 166 (44.9) 140 (37.6) 96 (25.9)
Conjunctival hyperemia 101 (27.2) 62 (16.8) 36 (9.7) 19 (5.1)
Foreign body sensation 38 (10.2) 13 (3.5) 11 (3.0) 0
Eye pain 36 (9.7) 16 (4.3) 4 (1.1) 4 (1.1)
Photophobia 32 (8.6) 4 (1.1) 7 (1.9) 1 (0.3)
Conjunctival hemorrhage 28 (7.5) 22 (5.9) 2 (0.5) 3 (0.8)
Eye irritation 26 (7.0) 27 (7.3) 6 (1.6) 4 (1.1)
Dry eye 25 (6.7) 15 (4.1) 12 (3.2) 7 (1.9)
IOP increased 22 (5.9) 8 (2.2) 19 (5.1) 8 (2.2)
Vision blurred 19 (5.1) 9 (2.4) 5 (1.3) 2 (0.5)
Corneal endothelial cell loss 18 (4.8) 1 (0.3) 11 (3.0) 1 (0.3)
Iritis 18 (4.8) 1 (0.3) 10 (2.7) 1 (0.3)
Punctate keratitis 16 (4.3) 18 (4.9) 1 (0.3) 7 (1.9)
Anterior chamber cell 14 (3.8) 1 (0.3) 7 (1.9) 0
Lacrimation increased 13 (3.5) 11 (3.0) 1 (0.3) 1 (0.3)
BID, twice daily; BimSR, bimatoprost sustained-release implant; IOP, intraocular pressure. Do not distribute, copy or publish
Re
su
lts
Corneal Endothelial Cell Density
Pooled study data, ARTEMIS 1 + ARTEMIS 2
Error bars show the standard deviation.
BID, twice daily; Bimatoprost SR, bimatoprost sustained-release implant; BL, baseline; CECD, corneal endothelial cell density; M, months; W, weeks.
44W 52W 20M0
500
1000
1500
2000
2500
3000
0 4 8 12 16 20 24 28 32 36 40 44 48 52 56 60 64 68 72 76 80 84 88
Mean
CE
CD
(cell
s/m
m2)
Time
Bimatoprost SR 10 ug (n=372)
Timolol BID (n=370)
Fellow eyes, all patients (n=1111) (treated with timolol BID)
BL 12W 28W 44W 52W 20M
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lts
Central Corneal Thickness and Visual Acuity StabilityWith Bimatoprost SR 10 µg
Pooled study data, ARTEMIS 1 + ARTEMIS 2
• No change in CCT and visual acuity in patients with corneal AEs
AE, adverse event; BCVA, best-corrected visual acuity; Bimatoprost SR, bimatoprost sustained-release implant; CCT, central corneal thickness..
All Patients(n=153)
Patients With Corneal AE (n=16)
Safety Parameter Baseline 20 Months Baseline 20 Months
Mean CCT (µm) 555.4 555.6 567.9 566.0
Mean BCVA (ETDRS letters) 82.7 83.5 83.1 83.4
Bimatoprost SR 10 µg Patients in the Dataset Who Had Completed 20 Months
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Clin
ical
Pro
gram Bimatoprost SR Clinical Trial Program
18
One Phase 1/2 Study Two Ph3 Studies (US) Two Ph3 Studies (EU)
OAG/OHT OAG OAG/OHT OAG/OHT
Comparator Topical Bimatoprost Timolol SLT
Duration 24 months 20 months 12 months
No. of Administrations 1 or 2 3 2-3
A P O L L
Ahmed, et al. AGS 2019 Do not distribute, copy or publish
Sum
mar
y• First-in-class sustained-release, biodegradable implant for the treatment of open-angle
glaucoma or ocular hypertension designed to lower IOP for at least 4 months while freeing patients from daily eye drop regimens
• In P3 and P1/2 studies, BimSR demonstrated an extended duration of effect of 1 year (83%) or 2 years (36%) in many patients
• Sustained IOP lowering may involve durable MMP-mediated remodeling of aqueous outflow
• The value of extended duration of effect is reduced treatment burden, improved adherence with more sustained pressure lowering, less hyperemia, less orbitopathy
• Empowers physicians by putting IOP control in their hands
Bimatoprost SR Risk/Benefit was favorable in both Phase 3 studies
NDA submitted
Bimatoprost SR
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Thank You to Patients and Investigators!
Over 1000 patients have been enrolled in Bimatoprost SR studies
to date at > 300 investigative sites in over 30 countries
Patients of Thomas Walters, MD, Austin, TX
Bimatoprost SR Investigator
Ahmed, et al. AGS 2019 Do not distribute, copy or publish