Ocular Therapeutix eyes FDA filing with ph. 3 wet AMD win over Eylea, but investors balk

Ocular Therapeutix reported a phase 3 win that it believes can validate its attempts to challenge Regeneron’s entrenched position in wet age-related macular degeneration (AMD) with investigational Axpaxli, a hydrogel version of Pfizer’s now off-patent kidney cancer med Inlyta (axtinib). 

The company compared Axpaxli, an intravitreal injection, to Regeneron’s leading Eylea (aflibercept) in its phase 3 SOL-1 study, finding that the drug met its primary endpoint of superiority at week 36 with “high statistical significance,” according to a Feb. 17 press release. 

But the results didn't appear to deliver what investors had expected. By midday Tuesday, the company's shares were down some 25%.

SOL-1’s primary endpoint assessing its performance versus Eylea was the proportion of study participants who maintained visual acuity, or a loss of fewer than 15 letters on a common vision test, from baseline at week 36. 

The result makes Ocular's drug the “first and only drug with a novel mechanism to successfully demonstrate superiority to an approved anti-VEGF treatment in an FDA-aligned study for wet AMD,” Arshad M. Khanani, M.D., who chairs the steering committee for Ocular’s SOL program, said in a statement.

The FDA and Ocular came to an agreement on the trial protocol in 2024, with a Special Protocol Assessment (SPA) clarifying eligible patients for the trial. The study involved 344 newly diagnosed wet AMD patients who were randomized after showing peak responses to two Eylea injections, reaching 20/20 vision or an improvement of at least 10 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters of best corrected visual acuity (BCVA), as well as other criteria. The trial population was “specifically selected to lose vision,” according to the company. 

At week 36 of the study, the proportion of patients who met the visual acuity standards was 74.1% in the Axpaxli arm compared to 55.8% in the Eylea arm, the biotech said, an observed difference of 18.3% and a risk difference of 17.5%.

The drug also met the bar for durability at week 52, as the proportion of Axpaxli-treated patients who maintained their vision by that time was 65.9% compared to 44.2% in the Eylea group, with the risk difference coming to 21%. 

The risk difference was the probability of maintaining vision in the treatment arm compared to the control arm as per the trial's pre-specified statistical model, according to Ocular. 

It’s the risk difference findings that may have sent the company's shares tumbling, as William Blair analysts point out that the difference may be “below what investors were looking for,” the analysts explained in a recent note to clients. 

However, the William Blair team sees the stock market reaction as “unwarranted,” as the study's real-world applicability was “always limited.” The results, instead, can provide reassurances surrounding the company’s ongoing SOL-R study, a second non-inferiority trial that is “far more relevant for real-world clinical practice,” the analysts note.  

“We nonetheless believe these are positive results, as the compression in effect size was driven by the control arm outperforming expectations rather than Axpaxli underperforming,” the analysts explained. 

Ocular’s chief medical officer Nadia Waheed, M.D., agrees, commenting that the new data “give us great confidence in the SOL-R non-inferiority study, which is being conducted in a population likely to be more stable and easier to control than SOL-1.”

The company plans to present detailed results from the SOL-1 study at an upcoming medical meeting later this month and will follow the study’s patients for safety until the end of week 104. The data from SOL-1 will be used to back up a new drug application with the FDA, subject to “planned formal discussions” with the agency, according to the biotech.

If approved, Axpaxli could be the first tyrosine kinase inhibitor (TKI) to launch in the indication, the company noted. SOL-R, meanwhile, is a “complementary” trial that should read out at the start of 2027.

Even so, taking on Eyea may be a tall task. The wet AMD superstar picked up $2.75 billion in 2025 sales, Regeneron recently reported. 

Meanwhile, Regeneron is working to grow the reach of its high-dose version of Eylea as it contends with Roche’s long-acting eye med Vabysmo. The new formulation allows the drug to be dosed every eight to 16 weeks after an initial treatment phase and comes in a monthly dosing option. 

Extended dosing was once the goal of a failed collaboration between Regeneron and Ocular, which partnered up in 2016 on a sustained-release version of Eylea using Ocular’s hydrogel delivery technology. In 2017, Ocular’s Eylea formulation was scrapped and the revised agreement to focus on an extended-delivery, intravitreal implant formulation of Eylea was formally abandoned by Regeneron in 2021. 

The canceled deal left Ocular with learnings acquired from using Regeneron’s Eylea molecule that could “become a valuable strategic driver,” former CEO Antony Mattessich said at the time. 

Ocular is further studying its Axpaxli in diabetic retinal disease, including non-proliferative diabetic retinopathy (NPDR). The company also markets a monthly insert called Dextenza that was approved in 2021 to treat eye itching associated with allergic conjunctivitis.