Sean Adrean, MD: Impact of Baseline VA on Aflibercept 8 mg Outcomes in DME

Aflibercept 8 mg exhibited clinically meaningful visual, anatomic improvements at Week 48 in patients with DME regardless of baseline visual acuity.

Highlights

0:08 Post-hoc analysis of PHOTON

1:00 Primary results in DME

3:11 Clinical profile of aflibercept 8 mg

3:52 Real-world application

4:35 Reducing treatment burden, extending intervals

5:39 Expectations for 2024

6:22 Concluding thoughts

Baseline best-corrected visual acuity (BCVA) did not impact meaningful visual and anatomic improvements in eyes with diabetic macular edema (DME) treated with aflibercept 8 mg, according to a posthoc analysis of the phase 2/3 PHOTON trial.

Presented at the 2024 Association for Research in Vision and Ophthalmology (ARVO) Meeting, the post-hoc analysis revealed patients with baseline BCVA ≥20/50 experienced numerically greater visual gains and improvements in central retinal thickness (CRT) than those with baseline BCVA ≤20/40 at Week 48.

In an interview with HCPLive, Sean Adrean, MD, Retina Consultants of Orange County, indicated more patients treated with aflibercept 8 mg at baseline BCVA ≤20/40 also maintained their randomized dosing intervals versus those with baseline BCVA ≥20/50 through Week 48.

“When we look at 8 mg of aflibercept, we could be confident looking at the results of this trial that whether or not patients have 20/50 vision or worse or 20/40 or better vision, we can treat these patients with these extending dosing intervals,” Adrean told HCPLive. “We know that they’re going to maintain good vision and have an excellent response, even if they are out at 12 or 16 weeks compared with the 2 mg aflibercept at the 8-week dose.”

The PHOTON trial was a double-masked, 96-week, non-inferiority trial that assigned eyes with DME to treatment cohorts of aflibercept 8 mg every 12 (Q12W) or 16 weeks (Q16W) after 3 monthly doses or aflibercept 2 mg every 8 weeks (Q8W) after 5 monthly doses. Dosing intervals were shortened at Week 16 if patients treated with aflibercept 8 mg met prespecified dosing modification criteria.

At baseline, the mean BCVA in the cohorts ranged from 55.1 to 57.8 letters in patients with BCVA ≥20/50 (n = 422) and 72.6 to 73.2 letters in those with baseline BCVA ≤20/40 (n = 236). Meanwhile, the mean CRT ranged from 472.7 to 491.5 µm in patients at baseline BCVA ≥20/50 and 400.6 to 411.1 µm in those with BCVA ≤20/40.

Upon analysis, at Week 48, the mean change in BCVA in the aflibercept 2 mg Q8W, aflibercept 8 mg Q12W, and aflibercept 8 mg Q16W cohorts were +10.7, +10.5, and +9.2 letters, respectively, in patients with baseline BCVA ≥20/50. For those with baseline BCVA ≤20/40, the corresponding changes were +6.0, +6.0, and +5.6 letters, respectively.

Meanwhile, the corresponding mean changes in CRT from baseline to Week 48 were –195.0 µm, –194.7 µm, and –172.6 µm in patients with baseline BCVA ≥20/50 and –99.4 µm, –134.1 µm, and –107.9 µm in patients with baseline BCVA ≤20/40.

Among the aflibercept 8 mg Q12W and Q16W cohorts, 88.8% and 84.7% of patients with baseline BCVA ≥20/50 maintained their randomized dosing interval through Week 48. For those with baseline BCVA ≤20/40, 94.6% and 96.6% maintained their intervals, respectively.

“Compared with other DME trials, a good 40% plus of these patients had previous treatment with anti-VEGF, so these weren’t treatment-naive patients,” Adrean told HCPLive. “To see these kinds of responses with extended dosing intervals is very heartening because we always wonder how patients are going to respond when they are not treatment-naive.”

Disclosures: Adrean reports financial support and consultant fees from Apellis, Genentech, Opthea, Regeneron Pharmaceuticals, and others.

References

_{Adrean S. Outcomes of patients with diabetic macular edema (DME) and baseline best-corrected visual acuity (BCVA) of 20/50 or worse or 20/40 or better who were treated with aflibercept 8 mg and 2 mg: a post hoc analysis of the phase 2/3 PHOTON trial. Poster presented at the Association for Research in Vision and Ophthalmology (ARVO) 2024 Meeting, May 5–9, 2024.}