Dr. Singerman, Final Results from Phase II Study of Squalamine

Dr. Singerman, Final Results from Phase II Study of Squalamine

Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
Conclusions
Final Results from a Phase 2 Study of Squalamine
Lactate Ophthalmic Solution 0.2% (OHR-102) in
the Treatment of Neovascular Age-related Macular
Degeneration (AMD)
Lawrence J. Singerman, MD, FACS
Retina Associates of Cleveland
Professor of Clinical Ophthalmology
Case Western Reserve University
and Bascom Palmer Eye Institute
2
Take Home Messages
Squalamine Lactate (OHR-102)
SQUALAMINE BACKGROUND
Anti-Angiogenic Mechanism
Growth factors
Capillary
formation
(VEGF, PDGF, bFGF, etc.)
Na
+
(Angiogenesis)
Endothelial
Cell
H
+
Sq
ua
lam
ine
Calmodulin
H
+
Na
+
Squalamine
Pump
chaperones
inhibited
calmodulin
HH
++
H
+
Control
Squalamine
FITC (green fluorescence) labeled anti-calmodulin antibody
treated
• Being developed by Ohr Pharmaceutical as an eye drop
• Awarded Fast Track designation for wet-AMD by the FDA in May 2012
Growth factor
signal is aborted
1
Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
Posterior Tissue Trough Levels
OHR-102 Mechanism of Action
Dosing Interval= QD 24 Hours, BID 12 Hours
*=p-value <.01 **=p-value <.001 (values vs day 1+Dosing Interval)
• Trough levels well in excess of Squalamine’s threshold level to inhibit tissue
angiogenesis
•Rapid uptake, more pronounced with higher frequency dosing
IMPACT Study Design
OHR-102 Topical Ocular Formulation
0
1
2
3
4
5
6
7
OHR-102 Eye drops BID
Emollient properties to
soothe ocular surface –
increased comfort in elderly
population
TransTrans-scleral
permeability into the
choroid
Improved residence time
on ocular surface
Vehicle eye drops BID
Minimization of
uptake into the
aqueous humor
Increased retention
time in posterior
sclera/choroid
Ranibizumab
Ranibizumab (PRN)
Key Exploratory Phase II Study Endpoints
Patient Disposition
2
8
9
Mos
Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
Number of PRN Ranibizumab Injections
Baseline Demographics (N=142)
OVERALL
STUDY
Age (mean, Years)
79
Female (%)
54
Male (%)
46
Baseline Vision (mean letters)
Central Retinal Thickness (mean
microns)
59.1
Classic lesions (%)
49
Occult lesions (%)
51
414
ITT Analysis
Overall Population (N=142)
OHR-102 (N=73) Vehicle (N=69)
Visual Outcome Data
Mean Change in VA – ITT Population
Overall
Age (mean, Years)
78.1
80.1
Female (%)
61.6
46.4
Male (%)
48.4
53.6
Baseline Vision (mean letters)
Central Retinal Thickness
(mean microns)
59.1
59.1
413
415
Classic lesions (%)
52
46
Occult lesions (%)
48
54
> 3 Line Gains – ITT Population
Overall
3
Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
ITT Analysis
Classic Containing Lesions (N=70)
Mean Change in VA – ITT Population
Classic Containing
OHR-102 (N=38) Vehicle (N=32)
Age (mean, Years)
76.9
79.3
Female (%)
47.4
46.9
Male (%)
52.6
53.1
Baseline Vision (mean letters)
Central Retinal Thickness
(mean microns)
54.8
56.3
442
419
> 3 Line Gains – ITT Population
Classic Containing
mITT Analysis (Completers)
Overall Population (N=128)
OHR-102 (N=65) Vehicle (N=63)
Mean Change in VA – mITT Population
Overall
Age (mean, Years)
77.1
80.0
Female (%)
60
43
Male (%)
40
57
Baseline Vision (mean letters)
Central Retinal Thickness
(mean microns)
58.8
59.9
421
412
Classic lesions (%)
57
44
Occult lesions (%)
43
56
> 3 Line Gains – mITT Population
Overall
4
Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
mITT Analysis (Completers)
Classic Containing Lesions (N=65)
Mean Change in VA – mITT Population
Classic Containing
ORH-102 (N=37) Vehicle (N=28)
Age (mean, Years)
75.9
79.1
Female (%)
45.9
42.9
Male (%)
54.1
57.1
Baseline Vision (mean letters)
Central Retinal Thickness
(mean microns)
54.5
57.0
446
416
> 3 Line Gains – mITT Population
Classic Containing
> 4/5 Line Gains – mITT Population
Classic Containing
Summary
Safety
5
Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
Limitations
Discussion
What is the “impact” of the
IMPACT study?
Discussion
Discussion
Disease Variability
Disease Variability
•
•
•
6
Classic Containing Lesions
< 9 Disc areas of CNV
SHRM on OCT
Final Results from a Phase 2 Study of
Squalamine Lactate (OHR-102) in the
Treatment of Neovascular AMD
June 2015
Lawrence J. Singerman, MD
Retina Associates of Cleveland
Visual Outcome – Occult CNV Area* < 10 mm2
Discussion
Mean Change in VA
Percent > 3 line Va Gain
* Regardless of presence of classic CNV
Conclusions
THANK
Conclusions
YOU
7