Intravitreal aflibercept injection showed early signs of activity for patients with moderately severe to severe nonproliferative diabetic retinopathy.
George D. Yancopoulos, MD, PhD
Intravitreal aflibercept (Eylea) injection showed early signs of activity for patients with moderately severe to severe nonproliferative diabetic retinopathy (NPDR), with indications of disease progression reversal, according to topline findings from the phase 3 PANORAMA study presented at the 2018 ARVO Annual Meeting.
At 24 weeks, 58% of patients in the aflibercept arm had a ≥2-step improvement from baseline in Diabetic Retinopathy Severity Scale (DRSS) compared with just 6% of patients receiving a sham. This improvement versus sham was highly statistically significant (P <.0001).
"This is the first time a therapy has demonstrated it can reverse disease progression in patients with moderately severe to severe non-proliferative diabetic retinopathy without diabetic macular edema, in a trial specifically designed to study this population," George D. Yancopoulos, MD, PhD, president and chief scientific officer of Regeneron, the company developing the drug, said in a statement when the news was announced in March.
The double-masked study enrolled 402 patients across 3 treatment arms. Patients received a sham injection (n = 123) or aflibercept at 2 mg every 16 weeks (n = 135) or every 8 weeks (n = 134). The 24-week assessment was the first analysis of the study, with another assessment of DRSS planned at week 52 for the primary endpoint and again at week 100 as a secondary endpoint.
Baseline characteristics were well balanced across arms in the study. The median age of patients was 55.7 years. The mean duration of diabetes was 14.4 years (±9.24), and the HbA1c was 8.5 mmol/mol. Most patients had type 2 diabetes (91.5%). The best-correct visual acuity (BCVA) at baseline was 82.4 letters (20/25) and the central retinal thickness was 247 μm. Baseline DRSS was level 47 for 75.1% of patients and level 53 for 24.9%.
By week 24, patients had received 4.4 injections across all aflibercept groups. Secondary endpoints were not yet available, and will be assessed at week 100. These analyses will focus on the development of DME, the need for laser treatment, and changes in BCVA.
"Patients in the trial continue to be evaluated to determine if Eylea can prevent progression to neovascular vision-threatening complications or diabetic macular edema," Yancopoulos said. "We look forward to sharing one-year results later this year."
In the VISTA and VIVID studies for aflibercept in diabetic macular edema (DME), the VEGF agent showed improvements in DRSS compared with laser photocoagulation, which is the current standard for NPDR. All patients in the study had DME and diabetic retinopathy, with the majority (77%) of patients enrolled having moderate-to-severe NPDR.
At week 100 in VISTA, which administered aflibercept every 4 weeks (q4w) and every 8 weeks (q8w), the DRSS improved by ≥2 for 28% and 32% of patients, respectively, with photocoagulation the improvement was 7%. At 100 weeks in the VIVID trial, DRSS improvements of ≥2 were 38% in both the q4w and q8w arms and 16% for laser.
The most frequent serious adverse event across these studies were cataracts, which occurred in 1% to 2.4% of patients in the aflibercept group and for 0.3% for the laser arm. In the PANORAMA study, the researchers noted that there were no new safety signals with aflibercept. At the 24-week timeframe, there was just one mild case of intraocular inflammation. This occurred for 0.085% of all total injections, which matches previous studies.
Based on the promising early findings from PANORAMA, Regeneron expects to file for approval for aflibercept in NPDR before the end of 2018. Aflibercept is currently approved for patients with neovascular age-related macular degeneration, DME, and for those with diabetic retinopathy in the context of DME.
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