Eylea HD Phase 3 Trial Meets Primary Endpoint in Patients with RVO
Regeneron announced the primary endpoint was met in the phase 3 QUASAR trial investigating Eylea HD (aflibercept) injection 8 mg for the treatment of patients with macular edema following retinal vein occlusion (RVO), including those with central, branch and hemiretinal vein occlusions.
In the trial, patients treated with Eylea HD every 8 weeks (after initial monthly doses) experienced noninferior vision gains compared to those treated with the approved monthly dosing regimen of Eylea (aflibercept) injection 2 mg, the current standard of care. These data will be submitted to regulatory authorities around the world, with a submission to the FDA planned for the first quarter of 2025.
“All currently FDA-approved anti-VEGF therapies for retinal vein occlusion require monthly dosing, which can be burdensome for a patient. These impressive data from QUASAR demonstrated that Eylea HD patients with retinal vein occlusion experienced improved vision with fewer injections than Eylea – which could offer a significant advancement in this treatment setting,” Seenu M. Hariprasad, MD, Chair of the Department of Ophthalmology and Visual Science, The University of Chicago, said in a company news release. “Furthermore, about 90% of Eylea HD patients were able to maintain 8-week dosing intervals through 36 weeks.”
QUASAR is a global, double-masked, active-controlled phase 3 trial evaluating the efficacy and safety of Eylea HD, compared to Eylea, in patients with RVO. Eylea HD patients were treated with an 8-week dosing regimen (after 3 or 5 initial monthly doses), and Eylea patients were treated every 4 weeks. The primary endpoint was met at 36 weeks, with both groups of Eylea HD patients achieving noninferior visual acuity gains compared to those receiving Eylea. Eylea HD results were consistent across patients with branch retinal vein occlusions, and those with central retinal or hemiretinal vein occlusions.
Outcomes at 36 weeks were as follows:
| EYLEA 4-week regimen (n=301) | EYLEA HD 8-week regimen after 3 initial monthly doses (n=293) | EYLEA HD 8-week regimen after 5 initial monthly doses (n=298) | |||
| Mean observed BCVA improvement | 17.8 letters | 17.0 letters | 19.1 letters | ||
| Least squares mean difference in BCVA improvement, primary endpoint (non-inferiority p-value)* | -0.1 (p<0.0001) | 0.8 (p<0.0001) | |||
| Mean observed BCVA | 72.0 letters | 72.8 letters | 74.6 letters | ||
| Patients maintained on every 8-week dosing interval | 88% | 93% | |||
BCVA: best corrected visual acuity
*Non-inferiority (1-sided) p-values are for the difference in least squares mean compared to EYLEA with margin of 4 letters. EYLEA HD groups met non-inferiority.
The safety profile of Eylea HD (n=591) was similar to Eylea (n=301) in QUASAR and remained generally consistent with the known safety profile of Eylea HD in its pivotal trials. Ocular treatment emergent adverse events (TEAEs) occurring in ≥5% of all Eylea HD patients included increased ocular pressure (5%), and there was one case each of endophthalmitis and retinal vasculitis. The rate of intraocular inflammation was 0.5% for Eylea HD and 1.3% for Eylea. Hypertension at baseline was present in 66% of Eylea HD patients and 62% of Eylea patients. Hypertension during the trial was reported in 8.1% of Eylea HD patients and 4.7% of Eylea patients. Thromboembolic events (APTC) occurred in 0.5% of Eylea HD patients and 1.7% of Eylea patients.
Eylea HD is being jointly developed by Regeneron and Bayer AG. In the US, Regeneron maintains exclusive rights to Eylea and Eylea HD. Bayer has licensed the exclusive marketing rights outside of the US, where the companies share equally the profits from sales of Eylea and Eylea HD.