Download Ivan Goldberg1, 2, 3,*, Guna Laganovska4, Renuka Bathija5

Glaucoma: Clinical Drug Studies and Clinical Trials; Poster P‐S‐094
Maintenance of IOP‐Reduction for 6 Months with a Single Dose of a Novel Topically Applied Bimatoprost Ocular Insert in Patients with Open‐Angle Glaucoma or Ocular Hypertension
Ivan Goldberg1, 2, 3,*, Guna Laganovska4, Renuka Bathija5, Michael Coote6, Yair Alster7, Anne Brody Rubin7, Eugene De Juan, Jr.7, Charles Semba7
1Discipline of Ophthalmology, University of Sydney, 2Glaucoma Unit, Sydney Eye Hospital, 3Eye Associates of Sydney, Sydney, Australia, 4Pauls Stradins
University Hospital, Riga, Latvia,
5Waverley Eye Clinic, Melbourne, Australia, 6Melbourne Eye Specialists, Melbourne, Australia, 7ForSight VISION5, Inc., Menlo Park, CA, United States
*Corresponding Author: Ivan Goldberg, [email protected]
RESULTS
BACKGROUND
Reduction of IOP is the only proven treatment to slow progression of
glaucoma; however, a common problem is poor patient adherence to daily
medications. Lack of adherence has correlated with progression of vision
loss. An unmet need exists for alternatives to daily eye drops in patients
with open-angle glaucoma (OAG) or ocular hypertension (OHT) to improve
treatment adherence.
43 subjects were screened and 27 subjects met eligibility (Table 1). Mean
diurnal IOP at washout was 23.9 mmHg and a mean diurnal IOP reduction of
4.7-6.5 mmHg was observed for 6 months (Figure 1). 8 subjects did not
complete the full 6-month treatment due to unintentional early exit by
investigator at month 4 (N=3), inadequate IOP control at month 5 (N=3), and
discomfort with insert (N=2; 1 at week 2, 1 at week 6).
A novel sustained-release bimatoprost ocular insert (Insert) that allows
continuous administration of bimatoprost for up to 6 months with a single
applied dose was evaluated. The Insert is constructed as a polymer /
bimatoprost matrix in a soft, compliant ring (~26 mm diameter) that is
applied to the ocular surface in the clinic and maintained under the eyelids.
The Insert is designed to elute preservative-free bimatoprost into the tear
film.
Ocular adverse events occurring in more than 3 subjects included eye
discharge (N=17), epiphora (N=10), hyperemia (N=9 subjects), and
discomfort (n=7). There was one non-ocular serious adverse event (whiplash
injury from motor vehicle accident) not-related to study treatment.
Table 1. Study Demographics
Our purpose is to present feasibility results with a 13 mg Insert in OAG/OHT
patients treated up to 6 months.
Two similar Phase 1b single-arm, open-label studies were conducted at a
total of four centers (in Australia and Latvia) evaluating the safety and
exploratory efficacy of a single applied 13 mg Insert (OU) without
concomitant topical eye drops in patients with OAG/OHT treated up to 6
months.
Bimatoprost ocular insert (HeliosTM):
1.
Insert is placed under upper lid:
Screening
43 (86 eyes)
70 (50-85)
22 (51%)
a,b
31 (62 eyes)
69 (50-85)
15 (48%)
27 (54 eyes)
69 (50-85)
12 (44%)
Per Protocol
aOf
the subjects who wore the 13 mg insert, 6 had also worn the lower dose inserts used earlier in
one of the two studies.
bOf the subjects who wore the 13 mg insert,3 subjects exited for discomfort prior to a full diurnal
IOP at Week 2 and did not have evaluable IOP data; 1 subject was censored by medical monitor for
mid-study addition of systemic steroids.
Key eligibility criteria were adult patients with OAG/OHT controlled on
monotherapy (IOP ≤18 mmHg) and washout IOP ≥22 and ≤34 mmHg; subjects
with prior incisional or laser surgery for glaucoma were excluded. Following
a 4-week washout period, eligible patients received a 13 mg Insert (OU) and
were followed for up to 6 months. Study visits were at weeks 2, 6; months 3,
4, 5, 6. Diurnal IOP (T=0, 3 and 6hrs), slit-lamp, BCVA, adverse events were
collected at all visits. The Insert was removed after 6 months. Mean diurnal
IOP measures were assessed through 6 months using descriptive analyses of
observed evaluable data (per protocol).
Fig. 1. Mean Diurnal Intraocular Pressure (IOP) with Insert
(N = 27 subjects, per protocol population)
26.0
24.0
mmHg (S.E.)
The bimatoprost ocular insert is applied after a drug washout period and IOP
was observed for 6 months following the single application (OU).
Female, n (%)
Enrolled
METHODS
INSERT & PLACEMENT
Subjects (N)
Age, mean
(range)
22.0
20.0
18.0
16.0
14.0
2.
Diurnal
Average
N (eyes)
Screening
Washout
Week
2
Week
6
Week
12
Week
16
Month
5
Month
6
16.3
23.9
17.4
18.2
18.8
18.7
19.2
18.8
54
54
52
52
50
49
43
37
Per Protocol Analysis Cohort: At 6 months, of the 54 eyes exposed to the 13 mg bimatoprost inserts, 37 remained in the
efficacy analysis. Of the 17 eyes not included in the analysis, 8 subjects (16 eyes) exited early (reasons cited above); 1
subject (1 eye) was censored after placement of a new insert (fresh dose) when the initial insert fell out.
Insert is placed under lower lid:
3.
Properly placed insert slightly visible
at caruncle:
4.
CONCLUSIONS
A single applied Insert in patients with OAG/OHT provided:
• Six months of clinically significant IOP reduction from a single Insert (OU);
• Mean diurnal reduction of IOP was 4.7 to 6.5 mmHg from washout;
• No unexpected safety events were observed.
The results demonstrate initial feasibility of a sustained delivery of topical
bimatoprost.
DISCLOSURES
Images courtesy of ForSight VISION5
Goldberg (Consultant to ForSight VISION5); Alster, de Juan, Rubin, and
Semba (ForSight VISION5 Founders or Employees)