Recent findings published in Eye offer an early look at the first real-world data of aflibercept 8 mg for the treatment of neovascular (wet) age-related macular degeneration (nAMD).
Real-world data?! How exciting… but first, a look at this drug.
Developed by Regeneron and Bayer AG, aflibercept 8 mg was approved by the FDA in 2023 under the brand name EYLEA HD.
Its indications: Wet AMD; diabetic macular edema (DME); diabetic retinopathy (DR); and—most recently—macular edema following retinal vein occlusion (RVO).
And its recommended dosing for wet AMD?
Per the drug’s prescribing information (PI): 8 mg (0.07 mL of 114.3 mg/mL solution) administered via intravitreal (IVT) injection every 4 weeks (monthly) for the first 3 months, followed by:
- 8 mg every 8 to 16 weeks (2 to 4 months)
Plus, the FDA approved an expanded dosing option for the therapeutic in November 2025 across all indications.
- That schedule: An every-4-week (monthly, in other words) dosing option for certain patients
Now, what should we know about this new research?
Published online just last week, the new results are based on 8-week data from the ongoing SPECTRUM study, referred to as the “first global real-world study” of the high-dose aflibercept therapeutic for wet AMD.
- Its design: A 24-month, prospective study (NCT06075147) in progress across 18 countries
- Initiated in February 2024 with an expected January 2028 completion
- Its participants: An estimated 2,500 treatment-naïve (TN) or previously-treated (PT) wet AMD or DME patients aged 18+ (see here for inclusion criteria), separated into four cohorts.
- Its setup: See here for a look at each participant group’s intervention/treatment plan.
And the outcome measures?
Measured from baseline to 12 months, the primary outcome is change in best-corrected visual acuity (BCVA), as measured via Early Treatment Diabetic Retinopathy Study (ETDRS) letters chart or Snellen chart.
Secondary outcome measures can be found here (and include central retinal thickness [CRT).
So what is this early data based on?
That would be the 8-week results of the first ~100 patients (aged ≥50) in each of two cohorts with either TN (n 114) or PT (n = 104) wet AMD,
See here for participants’ baseline characteristics.
- Notably: No intervention was included in the study.
Now to the data—starting with the injections.
After baseline until Day 70 (and with the first injection administered at baseline):
Patients received a mean ± SD (median) of:
- 3.0 ± 0.3 (3) injections in the TN cohort
- 2.6 ± 0.6 (3) injections in the PT cohort
Take note: The week 8 injection data included any injections received at week 8, while the week 8 outcomes reflected the number of injections administered prior to the week 8 visit.
Next up: Visual outcomes and CRT changes.
The mean (95% CI) change in VA from baseline at week 8 was
- +3.2 (1.2, 5.1) letters in the TN cohort
- 0.0 (−1.6, 1.6) letters in the PT cohort
And the mean change in CRT was:
- −115 (−141, −89) µm in the TN cohort
- −39 (−60, −19) µm in the TN cohort
What else?
Investigators also found that the number of patients in both groups without intraretinal or subretinal fluid actually increased from baseline to week 8 (see here and scroll down for a visual).
No intraretinal fluid
- In the TN cohort: 46.2% (baseline); 75.7% (week 4); 79.8% (week 8)
- In the PT cohort: 42.6% (baseline); 70.8% (week 4); 65.6% (week 8)
No subretinal fluid
- In the TN cohort: 21.3% (baseline); 74.3% (week 4); 82.8% (week 8)
- In the PT cohort: 36.3% (baseline); 62.5% (week 4); 58.8% (week 8)
Any adverse events to report?
Ocular treatment-emergent adverse events (TEAEs) and non-ocular TEAs occurred in:
- 2.6% and 3.9% as well as 4.4% and 0 patients within the TN and PT cohorts, respectively.
A couple of notes:
- Two ocular TEAEs in the PT cohort were determined to be study drug-related (increased intraocular pressure [IOP] and vitreous floaters; n = 1 each)
- No serious ocular or non-ocular TEAEs developed in either cohort—including no cases of intraocular inflammation (IOI)
Got it. And how do these findings compare to prior aflibercept 8 mg research?
The study authors noted that the therapeutic’s safety profile was “consistent with that reported for the PULSAR trial.”
Keep in mind: The PULSAR trial (NCT04423718) was a wet AMD-targeted phase 3 trial whose data (along with the DME-focused PHOTON trial) supported aflibercept 8 mg’s initial FDA approval.
- See here for our last reporting on it (extended 3-year data released in early 2025).
Any final takeaways?
Considering this is just 8-week data from the ongoing study—there’s definitely no final conclusions as of yet.
- In fact, the study authors made a note that the analyses are “exploratory only” and—considering the results are based on just ~100 from each cohort—“this patient subset may not be fully reflective of the overall global SPECTRUM nAMD cohorts.
So you know what that means: Keep an eye out for additional data from the study between now and its anticipated 2027 (primary completion) and 2028 (study completion) end dates.