Biopharmaceutical company Opthea Limited has completed enrollment for the phase 3 pivotal clinical trial evaluating sozinibercept, its lead investigational candidate, in combination with aflibercept for the treatment of wet age-related macular degeneration (AMD).
Let’s start with sozinibercept.
Sozinibercept (OPT-302) is the first anti-vascular endothelial growth factor (VEGF) “trap” agent designed specifically for the eye, working to bind and sequester both VEGF-C and VEGF-D—which then prevents the activation of VEGF receptors 2 and 3.
Taking into account the strength of Opthea’s phase 2b study data (see below for more detail) combining OPT-302 with ranibizumab (Lucentis; Genentech), an anti-VEGF therapy, it could lead to potentially better anatomic and visual outcomes.
To note, the therapeutic was granted Fast Track designation by the FDA in 2021 for wet AMD.
What makes it unique?
Per Opthea, OPT-302 is “the first and only drug with strong clinical evidence demonstrating visual acuity (VA) superiority in combination with standard of care anti-VEGF-A therapy for wet AMD” that is well-tolerated with a favorable safety profile.
Now before we get to this phase 3 trial …what did phase 2 data find?
The company released phase 2b trial (NCT03345082) data in February 2023 evaluating OPT-302 administered by intravitreal (IVT) injection once every month against ranibizumab.
Participants (treatment-naïve wet AMD patients) were given IVT injections of one of two OPT-302 doses(0.5 mg or 2 mg) combined with ranibizumab (0.5 mg)—or sham + ranibizumab (0.5 mg) every 4 weeks for 6 months of dosing.
And those findings?
The study met its primary endpoint of OPT-302 combination therapy demonstrating superiority in visual acuity (VA) at 24 weeks over ranibizumab alone.
Participants noted vision gains of 10+ letters and anatomical improvements in reducing vascular leakage and improved retinal drying as well as a favorable safety profile.
Gotcha. Now let’s talk phase 3.
The 2-year COAST (Combination OPT-302 with Aflibercept Study) program (NCT04757636) is one of two pivotal, phase 3, multicenter, double-masked, sham-controlled trials evaluating OPT-302 (2.0 mg)in combination with an anti-VEGF-A treatment (in this case aflibercept 2.0 mg [Eylea; Regeneron]) for wet AMD.
Note: the phase 3 ShORe (Study of OPT-302 in combination with Ranibizumab) program (NCT04757610) is investigating OPT-302 (2.0 mg) with ranibizumab (0.5 mg).
What’s the participant criteria?
The estimated 990 participants (aged 50+) have two requirements:
- Active subfoveal choroidal neovascularization (CNV) lesion or juxtafoveal CNV lesion with foveal involvement secondary to AMD in the study eye
- An Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) between 60 and 25 (inclusive) letters in the study eye.
Exclusion criteria, which included any previous neovascular AMD treatment, can be found here.
How is the study design set up?
Participants are divided into three groups (330 participants in each arm) of intravitreal injections:
- 2.0 mg aflibercept + standard dosing of 2.0 mg OPT-302
- Aflibercept administered at 4 weekly intervals for three treatments (12 weeks), then at 8 weekly intervals (40 weeks)
- OPT-302 administered at 4 weekly intervals (52 weeks)
- 2.0 mg aflibercept + extended dosing of 2.0 mg OPT-302
- Aflibercept + OPT-302 administered at 4 weekly intervals for three treatments (12 weeks), then at 8 weekly intervals (40 weeks)
- Sham + aflibercept combination administered at visits when OPT-302 is not
- 2.0 mg aflibercept with sham
- Aflibercept administered at 4 weekly intervals for three treatments (12 weeks), then at 8 weekly intervals (40 weeks)
- Sham administered at 4 weekly intervals
What’s being measured?
Per Clinical Trials, and similar to the phase 2b trial, the primary outcome is mean change in ETDRS BCVA letters, measured at baseline to Week 52.
Secondary endpoints, also measured from baseline to Week 52, include the number of participants gaining 10+ as well as 15+ ETDRS BCVA letters.
See here for details on all six secondary measures.
Gotcha. When can we expect data?
According to Opthea CEO Frederic Guerard, PharmD, the company is looking to complete enrollment in the ShORe pivotal in Q2 2024, “with a goal of communicating topline results for both trials by mid-2025.”
For reference: the COAST program is slated to conclude by December 2025 while the ShORe program is expected to be conclude by December 2024.
And lastly… what's the bigger picture for sozinibercept?
Charles C. Wykoff, MD, PhD, chief investigator of the COAST program and a member of Opthea’s Clinical Advisory Board, noted the potential significance of the biologic candidate:
“Sozinibercept, when used in combination with standard of care anti-VEGF-A treatment, has the potential to be the first therapy to achieve superior visual outcomes over anti-VEGF-A monotherapy and meaningfully improve outcomes for patients with wet AMD.” stated Dr. Wkyoff, a medical and surgical retina specialist and director of Research at Retina Consultants of Texas.