Sumit Sharma, MD: 6-Month Results from Phase 2 RIPPLE-1 Trial

An intravitreal sustained-release dexamethasone implant, IBE-814 IVT, improved vision and reduced treatment burden among patients with retinal vein occlusion (RVO) or diabetic macular edema (DME), according to new 6-month results from the first-in-human phase 2 RIPPLE-1 trial.

The 6-month data, presented at the 127th Annual American Academy of Ophthalmology (AAO) Meeting in San Francisco, California, showed all patient cohorts experienced a reduction in central subfield thickness (CST) and improvement or stabilization of best-corrected visual acuity (BCVA).

“The promise for patients is really the reduction in the treatment burden, because one thing they hate the most is how frequently they need to come in for injections,” Sumit Sharma, MD, an assistant professor of ophthalmology, Cole Eye Institute, Cleveland Clinic, told HCPLive. “Anytime we can reduce that with an adjunctive therapy, it’s helpful. I don’t think this would ever be a first-line therapy, but I do think it would be something to consider for patients who’ve had anti-VEGF and still have fluid or require very frequent treatment.”

The IBE-814 intravitreal implant is performed with a 30-gauge needle with a 6-mm implant, an advantage over a 22g x 6mm commercial dexamethasone implant. The implant has improved durability of 6–9 months and the smaller needle size is less invasive for patients.

The RIPPLE-1 study was the first-in-human study designed to evaluate the safety and efficacy of the IBE-814 intravitreal implant at 21 clinics across 4 countries. Inclusion criteria included a diagnosis of DME or RVO, age ≥45 years, visual acuity 20/40 to 20/320 (Snellen), and treatment-naive or previously treated.

Patients were randomized to receive either the low-dose (single 70 µg implant) or high-dose (2 x 70 µg implant) implants at baseline. Patients were followed weekly and then monthly, with retreatment eligibility based on prespecified retreatment criteria between months 5 and 12. A safety follow-up was performed for up to 18 months.

The RVO cohort included 10 patients in the low-dose cohort and 15 patients in the high-dose cohort; the DME cohort included 23 patients in the low-dose group and 12 patients in the high-dose cohort. Subjects were primarily phakic, particularly in the RVO cohort, and there was a mixture of treatment-naive and prior-treated subjects in the RVO and DME cohorts.

At 6 months, among patients with RVO, the mean change in CST was –148 µm in the high-dose cohort and –188 µm in the low-dose cohort. Changes in BCVA showed an improvement of +6.4 letters in the high-dose cohort and +5.5 letters in the high-dose cohort. A total of 2 patients in the low-dose cohort and 3 patients in the high-dose cohort required rescue.

For patients with DME, 6-month results showed a mean change in CST of –68µm in the low-dose cohort and –94µm in the high-dose cohort. The corresponding mean change in BCVA showed a difference, with a gain of +8.7 letters in the high-dose cohort and a loss of –1.9 letters in the low-dose cohort. However, Sharma noted that 8 patients in the low-dose cohort required rescue treatment, compared to only 1 in the high-dose cohort.

Safety data were consistent with other intravitreal steroids, with no serious ocular adverse events identified in the 6 months of study. Sharma noted a low rate of cataract formation in the first 6 months and no patient required surgical intervention for intraocular pressure (IOP).

There were no IOP elevations in the low-dose RVO group and all other subjects with IOP elevations required only eye drops for control, Sharma noted. The treatment burden was additionally reduced with IBE-814 intravitreal treatment.

Patients with RVO in the low-dose and high-dose cohort achieved a reduction in treatment burden of –76% and –88%, respectively. Patients with DME in the low-dose and high-dose cohorts achieved a reduction in treatment burden of –57% and –73%, respectively. Sharma noted approximately 67% to 100% of patients experienced a reduction in the treatment burden and an increase in visual acuity, depending on the dose cohort and disease status.

For more insight into the analysis, watch the full interview with Dr. Sharma.

References

^{Intravitreal Sustained-Release Dexamethasone Implant for Diabetic Macular Edema and RVO: Six-Month Results From the First-in-Human Phase 2 RIPPLE-1 Trial. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.}