Just days after reporting lackluster data from its latest phase 3 trial for wet age-related macular degeneration (AMD), Opthea Limited announced it will discontinue the retinal program for sozinibercept (OPT-302).
This news also comes with an update on the company’s second phase 3 trial (read on to learn about that).
First, a rundown of what led to this.
We’ll start with the candidate.
What it is: An anti-vascular endothelial growth factor (VEGF) “trap” agent, sozinibercept is specifically designed to be used in combination with standard-of-care anti-VEGF therapies.
Its mechanism of action: Works by combining with a VEGF-A inhibitor to block and then isolate both VEGF-C and VEGF-D (which are activated during wet AMD) from activating VEGF receptors 2 and 3.
- Why this is important: When activated, VEGF receptors 2 and 3 play key roles in wet AMD development via abnormal growth (choroidal neovascularization) and leakage of blood vessels.
And its clinical journey?
As we just covered last week, sozinibercept was most recently evaluated in the phase 3 Combination OPT-302 with Aflibercept Study Trial (COAST) study (NCT04757636).
This was the second of two phase 3 studies—with the other being the ShORe (Study of OPT-302 in combination with Ranibizumab [NCT04757610]) trial—for the candidate.
- The difference between the two: The COAST trial evaluated sozinibercept + aflibercept versus aflibercept alone, while the ShORe study (which is still ongoing, keep in mind) is evaluating sozinibercept + ranibizumab versus ranibizumab alone.
And see here for details on sozinibercept’s positive performance in prior phase 2b trials.
So what exactly led to this program discontinuation?
Quite simply: The COAST trial failed to achieve its primary endpoint. For all the details, check out this rundown.
And what’s this news about the ShORe trial you mentioned earlier?
Ah, yes. Unfortunately, the update on that isn’t any more positive for sozinibercept.
The move to end its wet AMD program was made in part due to not only the COAST trial’s disappointing outcome but also in light of accelerated topline data released from the ShORe trial (which the company had previously said would be reported mid-2025).
Details, please.
Opthea reported that similar to the COAST trial—and despite sozinibercept being well tolerated—the ShORE study “did not meet its primary endpoint of mean change in best-corrected visual acuity (BCVA) from baseline to week 52.”
The data: For wet AMD patients with minimally classic and occult lesions, participants receiving sozinibercept + ranibizumab every 4 weeks (Q4W) or every 8 weeks (Q8W) achieved a mean change in BCVA of:
- 13.3 letters from baseline to week 52 (Q4W; p-value = 0.35 )
- 12.9 letters from baseline to week 52 (Q8W; p-value = 0.19)
Comparatively: Patients receiving ranibizumab alone Q4W or Q8W achieved a mean change in BCVA of:
- 13.3 letters from baseline to week 52 (Q4W; p-value = 0.32 )
- 12.6 letters from baseline to week 52 (Q8W; p-value = 0.09)
And the company’s input?
CEO Frederic Guerard, PharmD, expressed Opthea’s disappointment and shared that, per its obligations under the development funding agreement (DFA) with investors of sozinibercept’s clinical development, they’ll continue to provide any potential future updates.
Important to note: The company emphasized that this decision “did not constitute a termination event under the DFA resulting in any amount payable by Opthea.”
Translation: Currently, the company does not need to repay investors for the sozinibercept development costs (as we previously discussed the possibility).
I’m sensing a ‘but’ …
Indeed. There still remains the possibility that—under certain circumstances or after terminating the DFA—Opthea may need to pay “a multiple of the amount funded by the DFA investors that would have a material adverse impact on the solvency of the company.”
See here for a look at what could trigger this.
Any cause for concern with the company’s future?
There is, actually. Although no specifics were given, Opthea shared that, in light of the wet AMD program’s discontinuation for sozinibercept, “there remains material uncertainty as to Opthea’s ability to continue as a going concern.”
- The company added that its ongoing discussion with its DFA investors will continue and, due to this, “Opthea cannot be certain as to the outcome of those discussions or when that outcome may become known.”
Stay tuned to hear more in the coming months.