Ocular Therapeutix (NASDAQ:OCUL) executives highlighted what the company described as a landmark Phase 3 outcome for its retinal disease candidate AXPAXLI and discussed ongoing development, safety questions, and regulatory strategy during RBC Capital Markets’ Ophthalmology Conference.
Company overview and Phase 3 program
Pravin Dugel, executive chairman, president, and CEO, said the company has advanced AXPAXLI into Phase 3 and recently completed SOL-1, which he characterized as “the first and only superiority study versus an anti-VEGF to succeed,” citing a p-value of 0.0006. Dugel said a second Phase 3 trial, SOLAR, is ongoing and the company has said publicly it is expected to read out in the first quarter of next year.
Comments on legal action and the importance of scientific dialogue
As an example, he referenced prior questions related to “floaters,” which he said were actually drug particles, and noted the company addressed those questions using what he described as 129 slides at a Macula Society symposium.
SOL-1: interpretation of efficacy and study design
Dugel said the medical community quickly recognized the significance of SOL-1’s superiority versus EYLEA, calling EYLEA a “phenomenal drug” and emphasizing the robustness of the p-value. He added that, in his view, additional analysis and presentations will reinforce two themes: disease control and durability. Dugel also said strategic interest increased after the superiority outcome and that sentiment improved following the company’s data clarification at the Macula Society meeting.
In discussing best-corrected visual acuity (BCVA) results and comparisons to other trials, Dugel pushed back on drawing parallels between SOL-1 and studies designed to show vision gains. He said SOL-1 was designed differently—selecting patients who were highly anti-VEGF dependent and, per the protocol framework he described, taking away drug to allow vision to decline before rescue—making comparisons to typical “vision gain” studies inappropriate.
Dugel also pointed to a Macula Society presentation by Dr. Adnan Tufail, stating that analyses across multiple datasets suggested a “ceiling effect” in patients who start with very good vision, and that AXPAXLI performed as well as it could given the patient selection in SOL-1. He said the talk concluded AXPAXLI’s performance was comparable to Lucentis in ANCHOR and MARINA with monthly dosing, given the high-vision population studied.
Looking ahead to real-world use, Dugel argued that clinical trial populations tend to be super-selected and said he believes AXPAXLI could perform better in routine practice than in SOL-1 because SOL-1 enrolled particularly challenging patients.
Potential real-world use and adoption
Asked about the possibility of initiating AXPAXLI in tandem with an anti-VEGF (two injections on the same day), Dugel said such an approach was “certainly not inappropriate,” but added that how clinicians will incorporate the therapy remains to be seen. He suggested that most early use may involve switching established patients who are frustrated with frequent injections, then cautiously extending treatment intervals as physicians gain comfort.
Dugel said he believes AXPAXLI could be used as a first-line therapy, referencing a limited number of treatment-naïve patients in an Australia study where it was used as monotherapy and performed as expected versus commercial-grade EYLEA or Lucentis, while acknowledging the small sample and that it was not the focus of the study. He added that clinicians often adopt approaches such as treat-and-extend even when not specified on labels, and said he expects rapid adoption as physicians “figure out” best practices.
Safety discussion: “floaters” as drug particles and expectations for SOLAR
On safety, Dugel addressed “floaters” reported in SOL-1 (12% in the treatment arm versus about 1% in control, as described by the moderator). He said the company’s position is that these were drug particles and that investigators were instructed to look for evidence of drug elution using indirect ophthalmoscopy, which he noted visualizes the far peripheral retina, away from the visual axis. He emphasized that reports were made by physicians, that the observations aligned with when the drug should be seen, and that there was no impact on vision. He also said there is no MedDRA code for “drug particle,” so physicians were asked to code the finding as floaters.
When asked whether the particles resolved, Dugel said they “behaved like a drug,” which would be expected to disappear, and indicated additional data would be presented soon at an upcoming Vitreous Society meeting in Las Vegas.
Regarding whether floaters could be more frequent in SOLAR given six-month dosing, Dugel said he does not expect it to be an issue for patients, reiterating the peripheral location and lack of impact on vision. He also noted that in SOL-1, all patients were redosed at week 52 and said the company has accumulated redosing experience in SOLAR. He added that a data safety monitoring committee is observing closely and said there have been “no issues whatsoever.”
Dugel said SOL-1 has also provided a basis for confidence in SOLAR, stating that if SOLAR’s rescue criteria had been applied to SOL-1, nearly 80% of SOL-1 patients would have been rescue-free. He argued this is notable because SOL-1’s patient population was, in his words, the “opposite” of SOLAR’s, while SOLAR includes an extended ramp period intended to select stable patients before randomization. He also noted SOLAR’s primary endpoint is at week 56, described it as a single endpoint, and said the U.S. non-inferiority margin is 4.5 letters, which he called the largest the FDA allows. For ex-U.S. regulators, Dugel said the company believes it is aligned but has not formally disclosed details of those discussions.
On regulatory strategy, Dugel reiterated that the company plans to file for FDA approval based on SOL-1 alone, without waiting for SOLAR. He said the company is “more confident than ever” in that approach, citing the study’s special protocol assessment (SPA) and the robustness of the superiority result. He also referenced FDA statements and a New England Journal of Medicine editorial discussing single-trial approvals, and said the company believes SOL-1 meets the expectations of a well-designed, well-masked, and properly powered study. Dugel said the process for a single-trial approval has already begun, but he declined to share specifics of ongoing FDA interactions, adding that he is pleased with the collaboration.
About Ocular Therapeutix (NASDAQ:OCUL)
Ocular Therapeutix, Inc is a biopharmaceutical company dedicated to the development of innovative therapies for diseases and conditions of the eye. Founded in 2011 and headquartered in Bedford, Massachusetts, the company focuses on sustained-release drug delivery platforms designed to address key unmet needs in ophthalmology. Its proprietary hydrogel-based inserts and sealants aim to improve patient compliance and outcomes by providing controlled release of active pharmaceutical ingredients directly to ocular tissues.
The company’s flagship product, DEXTENZA®, is a preservative-free, sustained-release dexamethasone intracanalicular insert approved by the U.S.
