Isarna Therapeutics presented final positive results from its Phase 2 BETTER trial at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting on May 6, 2025. The data showcased the potential of ISTH0036, a selective TGF-β2-blocking antisense oligonucleotide, in addressing retinal fibrosis in patients with wet age-related macular degeneration (nAMD) and diabetic macular edema (DME).
The international multicenter study evaluated ISTH0036 as a potential solution for retinal fibrosis, a significant unmet medical need not targeted by current anti-VEGF therapies. Prof. Marion R. Munk, Chief Medical Officer of Isarna Therapeutics, presented the findings at the annual meeting held in Salt Lake City, Utah.
Clinical Efficacy and Anatomical Improvements
Patients who received intravitreal injections of ISTH0036 every eight weeks (Q8W) demonstrated stable or improved best-corrected visual acuity (BCVA). All patient groups exhibited a reduction in central retinal thickness (CRT), indicating meaningful anatomical improvements in the retina.
Particularly noteworthy was the response in nAMD patients with fibrosis-associated hyperreflective material (HRM). These patients showed a significant decrease in HRM volume following ISTH0036 treatment, which contrasted sharply with increases observed in fellow eyes receiving standard anti-VEGF therapy.
In DME patients, ISTH0036 reduced intraretinal fluid volume in both treatment-naïve eyes and those previously treated with anti-VEGF therapy but showing inactive response. The treatment was well tolerated, with intraocular pressure remaining stable throughout the study period.
Targeting the Root Cause of Disease Progression
"The results from the BETTER trial underscore the potential of ISTH0036 as a first-in-class antifibrotic agent that directly targets TGF-β2-driven fibrosis—a key driver of disease progression in nAMD and DME," said Prof. Munk. "This is a promising advance toward transforming care for patients facing progressive vision loss despite optimal standard therapy."
TGF-β2 is a key cytokine involved in fibrosis and disease progression in retinal pathologies. By selectively suppressing its production, ISTH0036 addresses a fundamental mechanism of disease that current therapies do not target.
Study Design and Patient Population
The BETTER study evaluated ISTH0036 across clinical sites in Austria and India. The trial included both treatment-naïve patients and those previously treated with anti-VEGF therapy but showing inactive response. This diverse patient population helps establish the potential utility of ISTH0036 across different stages of disease and treatment histories.
Path Forward for Clinical Development
Following these positive results, Isarna Therapeutics plans to discuss their development strategy with regulatory authorities in both the United States and European Union. The company aims to advance ISTH0036 into Phase 2b/Phase 3 pivotal clinical studies, moving closer to potential regulatory approval.
If successful in later-stage trials, ISTH0036 could represent a significant advancement in the treatment landscape for retinal diseases, particularly for patients who continue to experience disease progression despite current standard-of-care treatments.
About Isarna Therapeutics
Isarna Therapeutics has built its foundation on expertise in antisense oligonucleotide design and therapeutic targeting of the TGF-β signaling axis. The company is advancing a pipeline of antisense compounds, with ISTH0036 representing their most advanced clinical candidate for retinal indications including wet AMD and DME.
The company's approach to targeting TGF-β2 specifically may have applications beyond retinal diseases, as this signaling pathway is implicated in a wide range of fibrotic and inflammatory conditions.
