Personalized treatment interval (PTI) dosing dynamics over 2 years in the phase 3 YOSEMITE and RHINE trials of faricimab in diabetic macular edema

Abstract

Purpose : Dual inhibition of the angiopoietin-2 and vascular endothelial growth factor (VEGF)-A pathways with faricimab may extend treatment durability beyond current anti-VEGF therapies for diabetic macular edema (DME). The PTI algorithm in the phase 3 YOSEMITE/RHINE trials was a protocol-driven treat-and-extend regimen, designed to test the durability of faricimab by tailoring dosing intervals to individualized treatment response.

Methods : YOSEMITE/RHINE (NCT03622580/NCT03622593) were randomized, double-masked, active comparator–controlled trials of faricimab for center-involving DME. Patients were randomized 1:1:1 to faricimab 6.0 mg per PTI after a minimum of 4 initial every-4-week (Q4W) doses, faricimab 6.0 mg Q8W after 6 initial Q4W doses, or aflibercept 2.0 mg Q8W after 5 initial Q4W doses. In the PTI arms, patients received faricimab Q4W until central subfield thickness (CST) < 325 µm was achieved at or after week 12. Once CST < 325 µm was achieved, treatment intervals could be extended by 4 weeks (up to Q16W), maintained, or reduced by 4 or 8 weeks (as low as Q4W), based on prespecified CST and best-corrected visual acuity (BCVA) criteria. To maintain masking, all patients received sham injections at non–active dosing visits; however, CST and BCVA at sham injection visits were not used to determine PTI dosing intervals. Treatment intervals in the faricimab PTI arms were assessed through week 100.

Results : Among 1891 patients enrolled in YOSEMITE (N = 940) and RHINE (N = 951), 313 and 319 patients, respectively, were randomized to the faricimab PTI arms. At week 52, > 50% of patients in the PTI arms achieved Q16W dosing and > 70% achieved Q12W or Q16W dosing. Approximately two-thirds of patients achieved Q12W or Q16W dosing without an interval reduction below Q12W through week 52 (YOSEMITE, 68%; RHINE, 64%). The majority of patients who rapidly achieved Q16W dosing at week 32 (ie, the first timepoint that a patient could be extended to Q16W dosing) subsequently completed a full Q16W dosing cycle and remained on Q16W dosing at week 52. Faricimab treatment intervals through week 100 and PTI case studies will be presented at the meeting.

Conclusions : Treat-and-extend–based PTI dosing in YOSEMITE/RHINE optimized treatment intervals and demonstrated the durability of faricimab to meet the heterogeneous needs of patients with DME.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.