YOSEMITE/RHINE: Faricimab Treat-and-Extend Shows Durability in DME Over 2 Years

Faricimab treat-and-extend supports the potential of dual angiopoietin-2 (Ang-2)/vascular endothelial growth factor-A (VEGF-A) inhibition to extend durability and reduce the treatment burden for patients with diabetic macular edema (DME), according to an analysis of the phase 3 YOSEMITE/RHINE trials.¹

The findings, presented at the 127th Annual American Academy of Ophthalmology (AAO) Congress in San Francisco, California, showed faricimab treat-and-extend dosing provided durable efficacy over 2 years of YOSEMITE and RHINE. More than half (56%) of faricimab treat-and-extend patients met extension criteria and could potentially extend to every 20-week dosing.

“Patients on every 12-week or more faricimab dosing intervals at week 96 exhibited stable disease control with robust anatomic and vision outcomes through 2 years,” noted the investigative team, led by Jennifer I. Lim, MD, University of Illinois at Chicago, on behalf of the YOSEMITE and RHINE investigators.

The analysis tested the durability of faricimab in DME using a treat-and-extend-based dosing regimen. Within the phase 3 YOSEMITE/RHINE trials, patients were randomized to faricimab 6.0 mg every 8 weeks (Q8W), faricimab 6.0 mg treat-and-extend (Q4W up to Q16W based on central subfield thickness [CST] and best-corrected visual acuity [BCVA] criteria), or aflibercept 2.0 Q8W through week 100 (pooled n = 1891).

In the faricimab treat-and-extend arms, 62% of patients achieved Q16W dosing and 78% achieved ≥Q12W dosing at Week 96. Most patients who achieved ≥Q12W dosing at week 52 (79%) maintained ≥Q12W dosing with no interval reduction below Q12W through Week 96, while a minority (8.6%) remained on ≤Q8W dosing through the 2-year trial. For this analysis, investigators assessed the efficacy outcomes of patients who ended the study on Q12W and Q16 W dosing intervals.

Within the analysis, the overall faricimab treat-and-extend cohort (n = 632) had a mean age of 62.2 years, 236 (37.3%) were female, and 489 (77.4%) were White. The mean BCVA was 62.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the mean CST was 478.5 µm.

Upon analysis, investigators observed robust and stable vision and CST improvements through 2 years in patients on Q12W or Q16W dosing at Week 96. The median number of intravitreal injections was 11 in the overall treat-and-extend cohort through year 2, 12 in the Q12W cohort and 10 in the Q16W cohort at the end of the study.

At an average of weeks 92 to 100, the overall treat-and-extend cohort (n = 632) experienced a mean BCVA improvement of +10.6 ETDRS letters, while the Q12W cohort (n = 88) experienced an increase of +13.7 ETDRS letters, and the Q16W cohort (n = 347) experienced improvements of +11.7 ETDRS letters. Regarding CST improvements, at weeks 92 to 100, the overall treat-and-extend group had a mean CST of –195.1µm, compared to –240.4µm in the Q12W cohort and –187.0 µm in the Q16W cohort.

According to the analysis results, Lim and colleagues noted more than half of faricimab treat-and-extend patients met the criteria for a potential Q20W extension. “At the end of the study, approximately 56% of faricimab treat-and-extend patients (n = 598) completed a Q16W cycle and met criteria for potential Q20W extension,” investigators wrote.

References

1. _{Lim J, Yonekawa Y., Figueroa M., Pearce I., Gibson K., et. al. Faricimab T&E-Based Dosing Dynamics in the Phase 3 YOSEMITE/RHINE Trials. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 3 – 6, 2023.}