CU06 Shows Potential as Oral Therapy for Diabetic Macular Edema

Oral CU06-1004 was linked to improvements in best-corrected visual acuity (BCVA) and positive anatomic changes in eyes with diabetic macular edema (DME), according to late-breaking data presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting.

In preclinical study data, CU06, a novel endothelial dysfunction blocker, was proven to stabilize damaged capillaries, reduce abnormal angiogenesis, and impede inflammatory activation. These Phase 2 data furthered these findings by demonstrating visual improvements and stabilization of central subfield thickness (CST) in DME.

“In summary, with the obvious shortcomings of the study not having a control, we can summarize the drug was safely taken orally for 12 weeks, there was a dose-dependent improvement in BCVA, and showed changes in metabolic and inflammatory biomarkers,” said presenting investigator Victor Gonzalez, MD, Valley Retina Institute.

The Phase 2a study was a proof-of-concept, multi-center, randomized, open-label, parallel-group clinical trial. Investigators sought to assess the efficacy and safety of orally administered CU06-1004 to improve CST and BCVA in eyes with center-involved DME and determine optimal dosage.

Criteria for inclusion included CST, as measured by the Zeiss Cirrus (≥290 µm in women or ≥305 µm in men) and Heidelberg Spectralis (≥305 µm in women or ≥320 µm in men), and a BCVA letter score of 34 to 83.

Those matching eligibility (n = 67) were randomized to CU06 100 mg, 200 mg, or 300 mg dosed once daily for 12 weeks over a 4-week follow-up. Efficacy and safety assessments were conducted at baseline and Weeks 4, 8, 12, and 16.

The study’s primary outcome comprised the mean change from baseline in CST at Week 12, while secondary outcomes involved the change in BCVA and blood biomarkers. Subgroup analyses were conducted according to treatment history, baseline BCVA, and CST.

At baseline, the mean CST was 399.1, 402,2, and 381.2 µm, respectively, for the CU06 100 mg, 200 mg, and 300 mg dose cohorts. After 12-week treatment, the analysis showed CST measures remained mostly stable, without further worsening.

Qualitative evaluation of OCT images, including thickness maps and foveal B-scans, categorized the degree of improvement into 5 levels. These data revealed a trend of numerically greater improvement with higher doses of CU06.

Further, for BCVA outcomes, the baseline mean for overall subjects in the study was 70 ETDRS letters, with a change from baseline to Week 12 of 1.9 to 2.5 ETDRS letters. In particular, individuals with baseline BCVA ≤69 experienced a dose-dependent improvement in BCVA of 4.3, 5.4, and 5.8 letters at the end of treatment, respectively, with gradual improvement during the treatment period.

In addition, changes in fasting glucose and tumor necrosis factor-alpha (TNF-α) levels showed a dose-dependent increase from baseline at Week 12.

Overall safety data indicated CU06 was well-tolerated, without drug-related serious adverse events (SAEs). There were no safety-related or tolerability-related trends of concern identified in the study data.

“With this in mind, we need to continue other studies to further evaluate the drug formulations and make sure we have a control,” Gonzalez added.

Reference

_{Gonzalez V. Phase 2a Study of CU06-1004, an Oral Endothelial Dysfunction Blocker For the Treatment of Diabetic Macular Edema (DME). Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}