Study Subjects

• Major Inclusion Criteria:
  • Age 18 and older with center involving macular edema secondary to diabetes type 1 or 2
  • Central subfield thickness (CST) of 325 micrometers or more AND BCVA of 25-73 ETDRS
  • Anti-VEGF treatment naïve eyes or previously treated greater than 3 months prior to day 1 of the study
• Major Exclusion Criteria:
  • High Risk PDR, tractional retinal detachment, preretinal fibrosis, or ERM
  • Intravitreal anti-VEGF, PRP, macular laser, or cataract surgery within 3 months of study
  • Other causes of macular edema
  • Uncontrolled glaucoma

Randomization Scheme/Study Interventions

• Randomized 1:1:1 to:
  • Intravitreal faricimab 6mg every 8 weeks (6 initial injections q4 weeks, then q8)
  • Intravitreal faricimab 6mg per personalized treatment interval (PTI) (4 initial injections, then PTI)
  • Intravitreal aflibercept 2mg every 8 weeks (5 initial injections q4, then q8)
• PTI regimen: automated, protocol-driven dosing regimen based on treat and extend. PTI group received q4week injections until CST < 325 microns at or after week 12.

Endpoints

• Primary Outcome: Mean change from baseline in BCVA at 1 year, averaged at 48, 52, and 56 weeks.
• Secondary Outcomes:
  • Proportion of patients in the faricimab PTI group receiving dosing at 4, 8, 12, and 16 weeks at week 52
  • Mean Change in CST at primary endpoint and over time
  • Proportion of patients without protocol defined diabetic macular edema over time
  • Patients with absence of intraretinal fluid over time
  • Two-step improvement in Diabetic Retinopathy Severity Scale (DRSS) at week 52
  • Safety endpoints: incidence and severity of ocular and non-ocular adverse events

Results

• Study Population: 951 patients enrolled (n = 317 faricimab q8 weeks, n= 319 faricimab PTI, n = 315 aflibercept q8 weeks). 950 (99.9%) in RHINE received at least one dose of study treatment.
• Primary Outcome Results:
  • Primary endpoint of noninferiority of mean change in ETDRS from baseline to year 1 was met between faricimab q8weeks or PTI and aflibercept q8weeks.
  • Mean change in ETDRS letters from baseline to primary endpoint: 11.8 in faricimab every 8 weeks group, 10.8 in faricimab PTI group, 10.3 in aflibercept q8weeks.
• Secondary Outcome Results:
  • Durability in faricimab PTI group: 157 (51%) patients achieved dosing every 16 weeks and 62 (20%) patients achieved dosing every 12 weeks. 64% of patients achieved q12 or q16 week intervals at week 52 without an intervention reduction.
  • Greater reductions in CST in faricimab groups compared to aflibercept q8weeks: -195.8 microns in faricimab q8weeks, -187.6 in faricimab PTI group, -170.1 in aflibercept q8weeks.
  • Higher proportion of patients with absence of protocol defined macular edema in faricimab groups compared to aflibercept (85-90% of faricimab every 8 weeks, 83-87% of faricimab PTI, 71-77% of aflibercept q8weeks).
  • Higher proportion of patients with absence of intraretinal fluid (39-43% of faricimab q8week, 33-41% of faricimab PTI group, 23-29% of aflibercept every 8 weeks group).
  • Rates of two-step improvement in DRSS: 44.2% of faricimab q8weeks, 43.7% of faricimab PTI group, 46.8% of aflibercept every 8 weeks.
• Safety Outcome Results:
  • Incidence of ocular events and serious ocular adverse events were similar between faricimab and aflibercept.
  • Incidence of intraocular inflammation was numerically higher in the faricimab group compared to aflibercept (n=3 (0.9%) faricimab q8 weeks and n=2 (0.6%) PTI versus n=1 (0.3%) aflibercept q8 weeks). All events in RHINE were mild or moderate.

Conclusions

• This study demonstrated non-inferiority in vision gains between faricimab every 8 weeks and PTI versus aflibercept, improved anatomical outcomes, and increased durability at year 1.