What Should I Know Before Starting Argus II Implantations?


Brian K. Do, MD The Retina Group of Washington IMG_20181026_173025.jpg Dr. Arshad Khanani, MD, of Sierra Eye Associates, in Reno, NV, presented these promising phase 2 data in one of the last presentations of Day 1 of Retina Subspecialty Day. He began by describing an unmet need in the treatment of neovascular AMD (nvAMD); while the use of anti-VEGF agents revolutionized the treatment of nvAMD and resultant visual outcomes, he asserted that these treatment regimens are associated with significant burden upon our patients due to the frequency of office visits and intra-vitreal injections. Therefore the search for longer-acting medications/agents has continued. Previous studies looking at quarterly dosing of ranibizumab have been undertaken, but showed discouraging visual acuity results (EXCITE). Further data from the AURA study additionally demonstrated that visual acuity in eyes with nvAMD correlates with the number/frequency of intra-vitreal injections of anti-VEGF agents. Faricimab, the first bispecific molecule designed for intravitreal use, has the ability to inhibit both VEGF, as well as Ang-2, levels of which have been shown to be elevated in the vitreous of eyes with nvAMD, and have been shown to be associated with vascular destabilization and microvascular inflammation. Additionally, the Fc portion of the molecule has been modified to decrease potential systemic exposure, and to reduce inflammatory potential. In regard to efficacy, we’ve seen benefits of VEGF/Ang-2 blockade in previous studies: in diabetic macular edema (DME) in the BOULEVARD study, as well as in AMD in the AVENUE study. The AVENUE data showed meaningful best-corrected visual acuity (BCVA) gains, and reduction in central subfield thickness (CST) on OCT. Of note is that in the AVENUE study, both q4week and q8week injections achieved BCVA gains similar to those seen with monthly intravitreal ranibizumab injections. STAIRWAY, in comparison to AVENUE, was designed to evaluate even less frequent injections of faricimab. Individuals were randomized to one of three treatment groups:
  • 4 monthly loading doses of faricimab, then q12week dosing
  • 4 monthly loading doses of faricimab, then q16week dosing
  • monthly ranibizumab
The results of the study can be summarized as follows:
  • The ranibizumab group exhibited overall worse visual acuity and increased CST on OCT prior to the initiation of treatment.
  • 65% of faricimab patients had no disease activity 12 weeks after the last of 4 loading doses (based on OCT, BCVA, and clinical assessment).
  • The maintenance of visual gains in both faricimab groups was similar to that seen in those randomized to ranibizumab.
  • The proportion of individuals who gained/maintained visual acuity was similar across all three groups.
  • The reduction of CST on SD-OCT was similar across all three groups.
  • Changes in choroidal neovascularization (CNV) lesion size were similar across all three groups.
There were no reported cases of endophthalmitis from within the study, and no new safety signals were reported overall. 1 case of mild iritis, and 1 case of mild anterior chamber flare were noted, but these did not appear to have any effect on the outcomes of the affected eyes. Dr. Khanani concluded that faricimab appears to reduce vascular destabilization and leakage in eyes with nvAMD, and that this molecule shows potential for increased durability. Faricimab certainly shows potential to become a valuable treatment option in eyes with nvAMD, and we should all look forward to seeing results of the global phase 3 program, which will begin next calendar year.