Melbourne biopharmaceutical firm Opthea has failed to meet the primary end point in a pivotal Phase 3 trial of its sozinibercept combination therapy for age-related macular degeneration (AMD), casting doubt over the company’s future.
A 24 March press release said the COAST (Combination OPT-302 with Aflibercept Study) trial was not able to show a mean change in best corrected visual acuity (BCVA) from baseline to week 52.
The study involved clinical trial sites around Australia and was investigating the superiority and safety of sozinibercept in combination with aflibercept, compared with standard-of-care aflibercept monotherapy.
After years of development and encouraging signs, the findings will come as a significant blow to the ASX- and Nasdaq-listed company, investors and the macular disease community.
Sozinibercept – a novel VEGF-C/D ‘trap’ fusion protein – was described as the only product in late-stage clinical development for nAMD with what Opthea said had the potential to be the first therapy in 20 years to deliver superior visual gains for patients suffering from the debilitating disease.
In December 2024, CEO Mr Fred Guerard told Forbes Australia he was “fairly confident” the therapy would be on sale and in paying customers’ eyes by early 2027. But warned: “As a biotech, I don’t know if you ever exit the valley of death. It’s a tough business. But we’re in a very good place.”
Dr Megan Baldwin has been the driving force behind the company, having led as CEO and managing director for almost 10 years, until October 2023. She stood aside for Guerard and became the chief innovation officer.
Opthea has since undertaken “a thorough review” of the Phase 3 COAST data to ensure both its accuracy and integrity, but no anomalies were found.
A statement said Opthea was now considering the impact of the “negative trial results” on the company itself as a going concern. It has an unaudited cash and cash equivalents balance of US$113.8 million (AU$181 m).
It has also been assessing its rights and obligations under its Development Funding Agreement. It may be required to pay up to US$680 million (AU$1.08 b) to development fund investors.
“In light of these updates, it is possible that under the DFA, Opthea could become required to pay amounts to the DFA investors that would have a material adverse impact on the solvency of the company,” the statement said.
“As previously disclosed, certain instances and events may result upon the termination of the DFA, and upon such termination, Opthea will be obligated to pay the DFA investors up to four multiples of the amounts paid to the company under the DFA.”
Termination can be triggered by a range of events, including, among other things, inability of Opthea to fund development costs, failure by Opthea to continue to use commercially reasonable efforts to develop sozinibercept, Opthea’s insolvency, or disagreement with the DFA investors.
At this stage, the company said no decision had been made both its Phase 3 trials, including whether to discontinue activities for the COAST trial or accelerate and unmask the ShORe trial in which sozinibercept with ranibizumab is being assessed.
“In light of these matters, there remains material uncertainty as to Opthea’s ability to continue as a going concern,” the company said.
Opthea has requested that trading in its listed securities continue to be suspended on both ASX and Nasdaq until further notice.
How the trial played out
The COAST trial evaluated the efficacy and safety of intravitreally administered 2 mg sozinibercept every four or eight weeks in combination with 2 mg aflibercept, as per label, every eight weeks after a loading phase for nAMD.
The trial did not meet its primary end point after nAMD patients, with minimally classic and occult lesions, receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=296) or every eight weeks (n=297) achieved a mean change in BCVA of 13.2 or 13.2 letters from baseline to week 52, respectively, versus 13.8 letters with aflibercept monotherapy (n=299, p-values of 0.59 and 0.62 respectively).
In the overall population, participants receiving sozinibercept combination therapy with a dosing regimen of every four weeks (n=333) or every eight weeks (n=330) achieved a mean change in BCVA of 13.5 and 12.8 letters from baseline to week 52, respectively, versus 13.7 letters with aflibercept monotherapy (n=330, p-values of 0.86 and 0.42 respectively).
The company reported “no numerical difference” in the key secondary endpoints. Sozinibercept combination therapy was well tolerated.
More reading
Opthea chooses non-proprietary drug name ‘sozinibercept’ for OPT-302
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New CEO as Opthea reveals leadership reshuffle
