EC-104 outperforms Ozurdex in phase 2 BETTIS-1 trial for anti-VEGF–resistant DME

Eclipse Life Sciences has announced positive topline results from BETTIS-1, its phase 2 trial comparing EC-104 fluocinolone acetonide (FA) extended release with Ozurdex (dexamethasone intravitreal implant 0.7 mg; AbbVie) in patients with diabetic macular edema (DME).¹ EC-104 is a fully biodegradable intravitreal corticosteroid implant designed to release drug for about 6 months. The readout comes 6 months after the company completed enrollment.²

Trial design

BETTIS-1 (NCT06536491) is a randomized, subject- and evaluator-masked, multicenter study of 2 doses of EC-104: a high-dose 0.14 mg FA implant (EC-104-6M) and a low-dose 0.092 mg FA implant (EC-104-4M).³ Approximately 75 patients were to be randomized 1:1:1 to EC-104 high dose, EC-104 low dose, or Ozurdex. The target was about 20 patients per arm with a positive therapeutic response who could be evaluated for efficacy.³

Eligibility was deliberately narrow. Patients needed a documented suboptimal response to intravitreal anti-VEGF therapy. They also needed to have received locally administered corticosteroids before without a clinically significant rise in intraocular pressure (IOP).³ Safety was the primary end point. Secondary end points examined treatment durability on spectral-domain OCT through week 24.⁴

Topline findings

According to Eclipse, both EC-104 formulations had a favorable safety profile compared with Ozurdex. Treatment-related adverse events were infrequent and no unexpected safety signals emerged.¹ The company reported superior, clinically meaningful improvements in BCVA and CST at 24 weeks versus the dexamethasone implant. Both EC-104 arms also showed sustained CST reductions through week 24, which matches the implant's intended 6-month release profile.¹ IOP outcomes were described as acceptable in both arms in this steroid-tolerant population.¹

Scott Cousins, MD, CEO and vice president for research and development at Eclipse, said the data make EC-104 highly competitive in the DME market. He pointed to its durability, consistent anatomic response, and safety profile as evidence that it could reduce treatment burden and justify moving to phase 3.¹

Victor H. Gonzalez, MD, a retina specialist and founder of Gulf Coast Eye Institute in McAllen, Texas, said a true 6-month sustained-release corticosteroid "will be a significant advancement for this population."¹

Where EC-104 could fit

The trial targets a group that retina specialists often struggle to treat. Anti-VEGF therapy remains first line for DME, but many patients respond only partly. In a 2023 Ophthalmology Times EyePod, J. Fernando Arevalo, MD, PhD, described DME as multifactorial: some cases are VEGF driven and others are inflammation driven, and the inflammatory cases tend to respond better to corticosteroids.⁵ On the same podcast, Nathan Steinle, MD, cited DRCR Retina Network Protocol I data. These showed that patients who responded poorly after 3 anti-VEGF injections generally stayed poor responders. He also acknowledged that clinicians often switch to steroids too late.⁵

Durability is where existing steroids fall short. In a 2023 Modern Retina panel, Carl Regillo, MD, FACS, FASRS, said the dexamethasone implant and off-label triamcinolone each give roughly 3 months of effect. He added that IOP checks limit how much treatment burden they actually remove.⁶ A biodegradable implant that lasts close to 6 months would sit between Ozurdex and the nonbioerodible fluocinolone implant, which can last up to 3 years.⁵

Caveats

The topline announcement includes no letter gains, CST values, adverse event rates, or P values. That makes it hard to judge how large the superiority over Ozurdex is or how well it holds up statistically. The study was also small and enriched for patients who had already tolerated steroids without IOP spikes. That likely favors the IOP results, and those results may not apply to steroid-naive patients or those with glaucoma risk. The analysis also included only patients with an early positive response at week 4.²

Next steps

Eclipse plans to discuss phase 3 development with regulators and expects to launch a pivotal program in 2027.¹ The company is also seeking partners to speed up late-stage development and commercialization. Full BETTIS-1 data will be presented at an upcoming ophthalmology meeting and submitted to a peer-reviewed journal.¹

Besides EC-104, Eclipse is developing EC-303 for intermediate dry age-related macular degeneration (AMD) and EC-501, a 6-month anti-VEGF candidate for wet AMD, DME, and macular edema following retinal vein occlusion.¹

References

1. Eclipse Life Sciences announces positive topline results from phase 2 BETTIS-1 study evaluating EC-104 for diabetic macular edema (DME). GlobeNewswire. Published October 15, 2026. Accessed October 15, 2026. https://www.globenewswire.com/news-release/2026/10/15/3381495/0/en/eclipse-life-sciences-announces-positive-topline-results-from-phase-2-bettis-1-study-evaluating-ec-104-for-diabetic-macular-edema-dme.html

2. Harp MD. Eclipse Life Sciences completes enrollment in BETTIS-1 phase 2 clinical trial. Ophthalmology Times. Published April 13, 2026. Accessed October 15, 2026. https://www.ophthalmologytimes.com/view/eclipse-life-sciences-completes-enrollment-in-bettis-1-phase-2-clinical-trial

3. EC-104 intravitreal implant for the treatment of diabetic macular edema (BETTIS-1). ClinicalTrials.gov identifier: NCT06536491. Accessed October 15, 2026. https://clinicaltrials.gov/study/NCT06536491

4. Crago SM. Eclipse Life Sciences enrolls and doses first patient in BETTIS-1 phase 2 clinical trial. Ophthalmology Times. Published August 17, 2024. Accessed October 15, 2026. https://www.ophthalmologytimes.com/view/eclipse-life-sciences-enrolls-and-doses-first-patient-in-bettis-1-phase-2-clinical-trial

5. Arevalo JF, Kaiser P, Steinle N. Diabetic macular edema – considering pathogenesis in treatment selection. Ophthalmology Times EyePod. Published October 18, 2023. Accessed October 15, 2026. https://www.ophthalmologytimes.com/view/diabetic-macular-edema-considering-pathogenesis-in-treatment-selection

6. Steinle N, Scott A, Regillo C, Rao P. Use of intraocular steroids in DME. Modern Retina. Published June 16, 2023. Accessed October 15, 2026. https://www.ophthalmologytimes.com/view/use-of-intraocular-steroids-in-dme