EX-99.2 3 d914960dex992.htm EX-99.2 EX-99.2
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Aerie Pharmaceuticals, Inc.
Additional Rhopressa™
Rocket 1 Analyses
and Path Forward
May 7, 2015
Exhibit 99.2

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Important Information
Any discussion of the potential use or expected success of our product candidates is
subject to our product candidates being approved by regulatory authorities.
The information in this presentation is current only as of its date and may have changed or
may change in the future. We undertake no obligation to update this information in light of
new information, future events or otherwise. We are not making any representation or
warranty that the information in this presentation is accurate or complete.
Certain
statements
in
this
presentation
are
“forward-looking
statements”
within
the
meaning
of the federal securities laws. Words such as “may,”
“will,”
“should,”
“would,”
“could,”
“believe,”
“expects,”
“anticipates,”
“plans,”
“intends,”
“estimates,”
“targets,”
“projects,”
“potential”
or similar expressions are intended to identify these forward-looking statements.
These statements are based on the Company’s current plans and expectations. Known and
unknown risks, uncertainties and other factors could cause actual results to differ materially
from those contemplated by the statements. In evaluating these statements, you should
specifically consider various factors that may cause our actual results to differ materially
from any forward-looking statements. These risks and uncertainties are described more
fully in the quarterly and annual reports that we file with the SEC, particularly in the sections
titled “Risk Factors”
and “Management’s Discussion and Analysis of Financial Condition and
Results of Operations.”
Such forward-looking statements only speak as of the date they are
made. We undertake no obligation to publicly update or revise any forward-looking
statements,
whether
because
of
new
information,
future
events
or
otherwise,
except
as
otherwise required by law.

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Background
There are three Phase 3 registration trials for Rhopressa™,
•
“Rocket 1,”
a 90-day efficacy trial, the results of which were initially
reported on April 23, 2015 and are further reported in this
presentation,
•
“Rocket 2,”
a 12-month safety trial with a 90-day interim efficacy
readout expected third quarter 2015, and
•
“Rocket 3,”
a safety-only study being conducted in Canada.
Rocket 1 clinical trial evaluated
•
the
ocular
hypotensive
efficacy
of
Rhopressa™
0.02%,
dosed QD,
versus Timolol, 0.5%, dosed BID, in patients with elevated
intraocular pressure (OAG and OHT) for 90 days
•
the ocular and systemic safety of Rhopressa™, 0.02% for 90 days

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4
Primary endpoint: Mean IOP at
Weeks 2 and 6 and Day 90
Patients with open angle glaucoma (OAG) or ocular hypertension (OHT)
with IOP >20 mmHg and < 27 mmHg
N=411 randomized at 36 sites
(370 subjects per protocol)
Timolol 0.5%
BID
Rhopressa™
Rocket 1 Trial Design
Rhopressa™
0.02% QD (PM)
Patients randomized
1:1

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Number
of
Early
Terminations
–
44
(Total
Rhopressa™
plus
Timolol)
31 in Rhopressa™, 13 in Timolol
Major
Reasons
for
Early
Termination
(Total
Rhopressa™
plus
Timolol)
* Adverse Events for Rhopressa™
included: Allergic conjunctivitis (2); Eyelid pruritus (2); Lacrimation increased (2); Angle
closure glaucoma (1); Conj. hyperemia (1); Conj. edema (1); Conj. Vasc. Disorder (1); Eye irritation (1); Eye pain (1); Eye
pruritus (1);  Eyelid edema (1); Iris adhesions (1); Iris bombe (1); Vision blurred (1); Decreased visual acuity (1); Diarrhea
(1); Dysphagia (1); Feel abnormal (1); Instill. site pain (1); Conjunctivitis (1); Hypersensitivity (1); Upper limb fracture (1);
Corneal staining present (1); Prostate cancer (1); Dermatitis (1)
Rocket 1 Trial Conduct
Adverse events* (55%)
Protocol violation (18%)
Withdrawal of consent (11%)
Lack of efficacy (7%)
Investigator decision (4%)

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Rocket 1 Study Endpoints
Efficacy:
•
•
•
IOP analysis stratified by baseline IOP above and below 24 mmHg
•
Mean change from baseline IOP
•
Mean percent change from diurnally adjusted baseline IOP
•
Mean diurnal and change from baseline diurnal IOP
Safety:
•
The primary efficacy endpoint is the mean IOP at the following time
points: 08:00, 10:00, and 16:00 at the Week 2, Week 6, and Day 90
visits
Secondary efficacy endpoints include:
Ocular and systemic safety measures

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Primary Endpoint: Topline Summary
Per Protocol population (baseline IOP < 27 mmHg)
Rhopressa™
did not meet criteria for non-inferiority to Timolol
Rhopressa™
mean difference from Timolol ranged from –0.5 to
+1.3 mmHg
Inferiority
was
driven
by
a
subset
of
Rhopressa™
patients
losing
efficacy over time (~ 20%)
“Drifter”
subset: Increase in IOP greater than 3 mmHg from week 2 to
month 3

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Summary Of Rhopressa™
Rocket 1 Efficacy
Results Based On Different Baseline IOPs
Baseline IOP (mmHg)
Non-inferiority
Numerical Superiority
<27
Did not meet
Met 2 time points
<26
Met
Met 4 time points
<25
Met
Met 7 time points
<24
Met
All (9 time points)
<23
Met
All (9 time points)
<22
Insufficient power
All (9 time points)

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Today’s Objectives
Rhopressa™
IOP-lowering dynamics
What happened between baseline IOP < 27 mmHg and
26 mmHg?
Next steps for Rocket 2
Next steps for Rocket 4
Next steps for Roclatan™

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Explanation of Increase in IOP
Week 2 to Month 3

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Baseline IOP < 24 mmHg (Pre-specified analysis)

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Rhopressa
TM
Efficacy In Subjects On
PGA
Prior
To Study: Baseline IOP < 24 mmHg
•
Prior PGA use produced enhanced IOP-lowering with Rhopressa
TM
at
weeks 2 and 6
•
IOP lowering at month 3 equivalent to IOP lowering in non-PGA subjects
•
Prior PGA use had no effect on Timolol efficacy

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Rhopressa
TM
Efficacy In Subjects Not
On
PGA
Prior To Study: Baseline IOP < 24 mmHg
•
No loss of efficacy seen from week 2 to month 3 for Rhopressa
TM
or Timolol

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Baseline IOP < 25 mmHg At All Time Points

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Baseline IOP < 25 mmHg At All Time Points
-1.3, 0.0)
(-1.6,
-0.2)
(-
1.7, -0.3)
(-1.4, -0.3)
-0.7, 0.7)
-0.9, 0.5)
(-
1.4, 0.0)
-0.9, 0.3)
(-
0.5, 0.9)
-0.8, 0.7)
-1.1, 0.3)
-0.7, 0.5)
(
(
(
(
(
(
(
Rhopressa     –
Timolol
(95% CI)
Mean Difference
95% CI
0.6
0.9
1.0
0.8
0.0
0.2
0.7
0.3
0.2
0.1
0.4
0.1
-
-
-
-
-
-
-
-
-
-
Mean IOP
Rhopressa
Timolol
N=107
N=120
Baseline
8:00 AM
22.3
22.5
10:00 AM
21.2
21.0
4:00 PM
20.6
20.4
Mean Diurnal
21.4
21.3
Day 15
8:00 AM
17.2
17.8
10:00 AM
16.1
17.0
4:00 PM
16.2
17.2
Mean Diurnal
16.5
17.3
Day 43
8:00 AM
17.8
17.8
10:00 AM
16.8
17.0
4:00 PM
16.5
17.3
Mean Diurnal
17.1
17.4
Day 90
8:00 AM
18.1
18.0
10:00 AM
17.3
17.4
4:00 PM
17.0
17.4
Mean Diurnal
17.5
17.6
TM
TM

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Rhopressa
TM
Efficacy
In
Subjects
On
PGA
Prior
To Study: Baseline IOP < 25 mmHg
•
Prior
PGA
use
produced
enhanced
IOP-lowering
with
Rhopressa
TM
at
weeks 2 and 6
•
IOP lowering at month 3 equivalent to IOP lowering in non-PGA subjects
•
Prior PGA use had no effect on Timolol efficacy

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Rhopressa
TM
Efficacy
In Subjects
Not
On
PGA
Prior To Study: Baseline IOP < 25 mmHg
•
No
loss
of
efficacy
seen
from
week
2
to
month
3
for
Rhopressa
TM
or
Timolol

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Rhopressa
TM
IOP-lowering Effect Enhanced In
Subjects On PGA Therapy Prior To Study Entry
Prospective (pre-specified) analysis by pre-study medication status
showed
that
prior
PGA
use
enhanced
Rhopressa
TM
IOP-lowering
at
week 2 (p=0.003)
The PGA effect is lost over time, which we believe creates a false
impression that Rhopressa
TM
loses efficacy over time
The
apparent
PGA
synergy
with
Rhopressa
TM
is
greatest
at
week
2
and lessens over time in the absence of PGA dosing
No evidence of enhanced efficacy in Timolol subjects on PGA therapy
prior to study entry
Retrospective analysis of Phase 2 trial results shows prior PGA use
enhanced Rhopressa
TM
IOP-lowering by 1 mmHg (p=0.007) and     
1.2 mmHg (p=0.002) at weeks 2 and 4, respectively, relative to
subjects not previously on PGA

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What happened between baseline IOP of
26 mmHg and less than 27 mmHg?

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Rocket 1 Rhopressa
TM
Drifters
IOP increase from week 2 to month 3 greater than 3 mmHg
Correlation with entry baseline IOP
•
<27 mmHg –
36 drifters (n=182, 19.8%)
•
<26 mmHg –
18 drifters (n=133, 13.5%)
•
<25 mmHg –
12 drifters (n=107, 11%)
•
<24 mmHg –
5 drifters  (n=76, 6.6%)

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Baseline IOP < 27 mmHg At All Time Points

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Baseline IOP < 27 mmHg –
Drifters Removed

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•
Higher baseline IOP and average duration of disease 3 years longer
•
Potential for more severely diseased trabecular meshwork
•
Highly variable IOP
•
56% showed IOP decreases at week 2 of 5 –
11 mmHg
•
31% showed decrease in IOP at week 2, an unusual IOP rise above
baseline IOP at week 6, then IOP decreased again at month 3
•
Variability of IOP between Rhopressa™
studies (Phase 2 vs. Rocket 1)
•
22/36 (61%) drifters clustered at 5 (14%) study sites
•
Higher incidence (28%) of noncompliance compared to non-drifters
•
Impact of prior IOP lowering medication on week 2 IOP reading
•
66% PGA
•
34% None or Non-PGA
Rhopressa™
Drifter
Characteristics

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Variability of Baseline IOP Between Studies
Phase 2
Max entry IOP <36 mmHg
Rocket 1
Max entry IOP <27 mmHg
Same subjects had baseline IOPs ~2 mmHg higher in previous
Phase 2 studies vs. Rocket 1 study (n=71)
Phase 2 studies
Rocket-1

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Rhopressa™
Dosing
Compliance
Week
6
to
Month 3
Missed >35% of PM Doses
Drifters
Non-Drifters
Number non-compliant
10/36
4/30
% Non-compliant
28%
13%
Average days of dosing missed
per non-compliant subject
28/47
21/47
Average % days of dosing missed
per non-compliant subject
59%
45%
Compliance with dosing determined by bottle weight
Drifter subjects twice as likely to be non-compliant than non-drifters
More doses missed by non-compliant drifters than non-compliant    
non-drifters

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Summary Of Rocket 1 Observations
At
baseline
IOP
<24
mmHg
and
<25
mmHg,
Rhopressa™
subjects
on
non-PGA therapy or no therapy prior to study entry showed consistent
IOP lowering over time (no drift)
Prior PGA users showed a residual PGA effect that enhanced
Rhopressa™
IOP
lowering
at
week
2,
creating
a
false
impression
of
loss of Rhopressa™
efficacy by month 3
Rhopressa™
demonstrated
equivalent
IOP
lowering
at
month
3
in
prior
PGA
and
non-PGA
users
at
baseline
IOP
<24
mmHg
and
<25
mmHg
At higher
baseline
IOPs,
part
of
the
reduced
Rhopressa™
efficacy
over
time
may
be
due
to
a
minority
of
patients
with
severely
diseased
TM
or non-dosing compliance, etc.
The
potential
synergistic
effect
of
PGA+Rhopressa™
is
a
positive
for
both Rhopressa™
and Roclatan™

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Path Forward: Rocket 2
•
FDA meeting to discuss changing the Rocket 2 IOP range for the
primary endpoint to either baseline IOP < 24 mmHg or < 25 mmHg
•
Precedent for changing primary endpoint within ophthalmology:
Zioptan
–
for
treatment
of
glaucoma,
approved
February
2012
•
Outcome dependent not only on FDA discussions but also the power
adequacy at < 24 mmHg and < 25 mmHg based on patient enrollments
•
Aerie
has
the
ability
to
increase
patient
enrollment
if
required
because
database is not locked
•
Expect
Rocket
2
efficacy
results
in
Q3
2015
assuming
no
increase
in
enrollment
required
–
otherwise
by
year-end
2015

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Path Forward: Additional Rhopressa™
Phase 3
Trial, “Rocket 4”
•
Rocket 4 planned for Q3 2015
•
Primary endpoint: baseline IOP < 24 mmHg or < 25 mmHg at 9
time points through Day 90
•
Secondary endpoints below 27 mmHg and potentially month 6
efficacy
•
Expect to file the Rhopressa™
NDA in the first half of 2016 if we
don’t need additional patients in Rocket 2 or don’t need to wait
for Rocket 4 results –
otherwise by the end of 2016

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Path Forward: Roclatan™
First Phase 3 registration trial “Mercury 1”
to commence in Q3 2015
Final IOP range to be determined
Trial design is superiority of Roclatan™
over each individual component
Remaining Phase 3 trials (US+EU) to commence post-Rocket 2 topline
results

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