Ziv-aflibercept for DME provides BCVA gains, lower dosing burden

Results of a 1-year randomized controlled trial investigating treatment for diabetic macular edema (DME) show that intravitreal ziv-aflibercept (Zaltrap, Sanofi Genzyme) 1.25 or 2.5 mg is safe, according to Masoud Soheilian, MD.

In addition, when compared with intravitreal bevacizumab (Avastin, Genentech), it provides significantly greater improvement in best-corrected visual acuity (BCVA) with a lower dosing burden, said Dr. Soheilian, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The double-blind study also found that the functional benefit of ziv-aflibercept over bevacizumab was particularly seen in eyes with BCVA ≤20/50.

Anatomical data showed that ziv-aflibercept 2.5 mg was associated with significantly greater reduction in central macular thickness (CMT) compared with both the lower dose of ziv-aflibercept and bevacizumab.

“DRCR.net Protocol T demonstrated that intravitreal aflibercept (Eylea, Regeneron) was more effective than bevacizumab and ranibizumab (Lucentis, Genentech) for improving vision in DME patients with baseline BCVA ≤ 20/50,” Dr. Soheilian said.

“Based on our results, ziv-aflibercept seems to be a potential and cost-effective substitute for aflibercept in the same way that bevacizumab is a cost-effective substitute for ranibizumab,” Dr. Soheilian said. “Since vision improvement is the surrogate endpoint and because it is presumably safer to use a lower dose, we suggest using ziv-aflibercept 1.25 mg for treatment of DME.”

Ziv-aflibercept has the same molecular structure as aflibercept and acts by the same mechanism as a soluble decoy receptor, neutralizing all VEGF-A isoforms. In their commercially available formulations, the two products differ in osmolality, with the value being much higher for ziv-aflibercept compared with aflibercept-820 versus 250 mOsm.

“It has been shown that the higher osmolality of ziv-aflibercept may have a more damaging effect on the retina and cause retinal detachment,” Dr. Soheilian said. “However, we did not observe any such complications in our study.”

Other recent studies also show intravitreal ziv-aflibercept is safe and effective treatment without causing ocular toxicity in eyes with retinal disease, Dr. Soheilian noted.

Randomized control trial details

The study recruited 135 eyes of 93 patients that were randomly assigned to intravitreal treatment with ziv-aflibercept 2.5 mg/0.1 mL, ziv-aflibercept 1.25 mg/0.05 mL, or bevacizumab 1.25 mg/0.05 mL. Ziv-aflibercept was administered as three loading doses at 4-week intervals and then every 8 weeks. Bevacizumab was administered on a monthly basis.

A total of 123 eyes (83 patients) completed all visits. No eyes required retinal photocoagulation, vitrectomy, or cataract surgery. The mean number of injections administered was about 6.7 in each of the ziv-aflibercept groups and 11.6 for bevacizumab.

BCVA analyses showed that compared with the bevacizumab-treated eyes, mean BCVA improvement in the 2.5 and 1.25 mg ziv-aflibercept groups was 0.20 and 0.16 logMAR greater, respectively. Percentages of eyes achieving >0.2 logMAR improvement of BCVA was also significantly greater in the ziv-aflibercept groups.

Among eyes with initial BCVA ≤20/50, a 2-line improvement in BCVA was achieved in 95% of eyes treated with ziv-aflibercept 2.5 mg, 91% of those treated with ziv-aflibercept 1.25 mg, and 67% of bevacizumab-treated eyes.

Overall, final CMT was <250 µm in 65% of eyes treated with ziv-aflibercept 2.5 mg, 53% of the eyes treated with ziv-aflibercept 1.25 mg, and 40% of bevacizumab-treated eyes.

For the subgroup of eyes with initial BCVA of 20/30 to 20/40, all treatments were associated with a statistically significant improvement in BCVA and a statistically significant reduction in CMT at 1 year. The improvement in BCVA and in CMT was significantly greater with ziv-aflibercept 2.5 mg versus 1.25 mg. There were no significant differences comparing the ziv-aflibercept groups with bevacizumab.

For eyes with initial BCVA ≤20/50, all treatments resulted in significant reduction in CMT at 1 year, and the effect was significantly greater in eyes treated with ziv-aflibercept 2.5 mg versus bevacizumab.

Dr. Soheilian has no relevant financial interests to disclose.