26th July, 2016
Melbourne, Australia, July 26 2016 – Opthea Limited (ASX:OPT)
• Phase 1 dose escalation study met primary objective demonstrating OPT-302 safety and tolerability as monotherapy and in combination with standard of care Lucentis®
• Changes in visual acuity (VA) and anatomic improvements on SD-OCT following the 3 month multiple dosing period demonstrate clinical activity of OPT-302 in both treatment naïve patients and prior treated patients
• Encouraging results suggest that combined inhibition of VEGF-C/D and VEGF-A may lead to improved outcomes over Lucentis® alone
• Results represent an important milestone for Opthea
• Opthea is actively accruing patients into Phase 2A dose expansion cohorts and planning for initiation of a randomised controlled Phase 2B clinical study in wet AMD patients in 2017
Opthea Limited (ASX:OPT), a developer of novel biologic therapies for the treatment of eye diseases, today announced positive data from its ongoing first-in-human clinical trial of OPT-302, a novel VEGF-C/D ‘Trap’ therapy for wet age-related macular degeneration (wet AMD). The Company will host a conference call and webcast at 10:30am Australian Eastern Daylight Time (8:30pm US EDT) today.
To access the live webcast, please visit the Presentations page of the Opthea website at http://www.opthea.com/presentations/. Alternatively, you may access the live conference call by dialling (888) 576-4387 (U.S.) or (719) 325-2244 (Australia & international) and using conference ID 4334252. An audio archive of the webcast will be available following the call at http://www.opthea.com/presentations/.
The study is being run under an Investigational New Drug (IND) program with the Food and Drug Administration (FDA) at 14 sites across the U.S. (ClinTrials.gov ID#: NCT02543229). The first-inhuman trial of OPT-302 comprises two parts: a sequential dose escalation (Phase 1, 20 patients) and a randomised dose expansion study (Phase 2A, up to ~30 patients) in patients that have either not been treated previously (treatment naïve patients) or who have demonstrated a sub-optimal response to prior anti-VEGF-A therapy.
The Phase 1 dose escalation enrolled 20 patients (mean age 74.8 years) into three OPT-302 dose level groups (0.3, 1 or 2 mg) in combination with Lucentis® (0.5 mg) and an OPT-302 monotherapy group (2 mg). Patients received three intravitreal injections of OPT-302 either alone or in combination with Lucentis® at 4 week intervals, with a week 12 follow-up visit one month after the third dose. For patients who received OPT-302 monotherapy, Lucentis® rescue therapy was provided at investigator discretion or if patients had a ≥5 letter decrease in vision and no reduction in central subfield thickness (CST) of at least 10% with presence of fluid. All cohorts enrolled 2 naïve patients and 3 patients who had received prior anti-VEGF-A therapy, with the exception of cohort 2 (OPT-302 1.0 mg + Lucentis®), which enrolled 5 previously treated patients.
The Phase 1 dose escalation study met its primary objective, with OPT-302 demonstrating safety and tolerability both as monotherapy and in combination with standard of care Lucentis®. Specifically, no dose limiting toxicities and no treatment-related serious adverse events were observed through week 12 of the study.
Secondary endpoints, which included changes from baseline in best corrected visual acuity and anatomic measures (central subfield thickness (CST)) on spectral domain-optical coherence tomography (SD-OCT) through week 12, demonstrated encouraging clinical activity of OPT-302 in both treatment naïve patients and those who showed a sub-optimal response to prior anti-VEGFA therapy. Overall, a majority of patients (16/19 evaluable at week 12) maintained or gained vision by week 12 compared to baseline and the other 3 patients that all received combination OPT-302 + Lucentis® therapy did not lose more than 3 letters (range -2 to -3 letters).
The mean gain in visual acuity overall from baseline at week 12 in treatment naïve patients who received OPT-302 + Lucentis® was 16.5 letters (n=4) and 9.5 letters in the 2 mg OPT-302 + Lucentis® dose cohort (n=2). The mean visual acuity gain from baseline at week 12 in patients who showed a sub-optimal response to prior anti-VEGF-A therapy was 4 letters with combination OPT-302 + Lucentis® (n=10 evaluable patients; mean number of prior treatment injections = 10.5, range 3 – 55).
The mean central subfield thickness (CST), a measure of the average retinal thickness at the centre of the retina, decreased in all combination OPT-302 + Lucentis® treatment groups at week 12, with a mean reduction from baseline of 214 µM (42.7%) in treatment-naïve patients (n=4, mean baseline CST 501.7 µM) and 42 µM (10.8%) in patients who showed a sub-optimal response to prior anti-VEGF-A therapy (n=10 evaluable patients, mean baseline CST 394 µM).
In the OPT-302 monotherapy cohort, 3/5 patients (1 naïve and 2 prior treated) did not require rescue with anti-VEGF-A therapy. At week 12, in patients that did not undergo rescue, there was a mean visual acuity gain of 3.3 letters from baseline (range 2 to 6 letters) and a mean increase in CST of 18 µM.
Dr. Pravin Dugel, managing partner of Retinal Consultants of Arizona and clinical professor at the University of Southern California Eye Institute, Keck School of Medicine, and member of Opthea’s Clinical Advisory Board, commented “Combination therapy with OPT-302 and standard of care Lucentis® is both feasible and well tolerated in patients who are either naïve to treatment or resistant to prior therapy. Although the preliminary clinical activity data to date is based on a small number of patients, the promising gains in vision and anatomic improvements on SD-OCT that have been observed suggest that combined inhibition of VEGF-C/D and VEGF-A may lead to improved outcomes over Lucentis® alone.”
Data from the 20 patient Phase 1 dose-escalation study is planned to be presented at the EU Retina conference in September 2016.
Dr. Megan Baldwin, CEO and Managing Director of Opthea, stated “I am delighted that we have achieved the outcomes and expectations of this phase 1 dose escalation study and demonstrated the potential of OPT-302 to improve clinical outcomes for wet AMD patients.”
“We are currently actively accruing up to ~30 additional patients into the Phase 2A dose expansion study cohorts. We look forward to monitoring the clinical outcomes to further build on our understanding of the mechanism of OPT-302, its safety profile and clinical activity, particularly in combination with Lucentis®.”
Dr. Pravin Dugel concluded that “While we expect that the OPT-302 data will continue to evolve as more patients are enrolled in the Phase 2A trial, the early evidence of an additive benefit of OPT-302 observed in this study is very promising and warrants further investigation of OPT-302 in a large randomised controlled clinical study in wet AMD patients.”
Company & Media Enquiries:
Megan Baldwin, PhD
CEO & Managing Director
Opthea Limited
Tel: +61 (0) 447 788 674
megan.baldwin@opthea.com
Australia:
Rudi Michelson
Monsoon Communications
Tel: +61 (0) 3 9620 3333
U.S.A. & International:
Candice Knoll
Blueprint Life Science Group
Tel: +1 415 375 3340, Ext 4
cknoll@bplifescience.com
