Key Takeaways

  • Innovent Biologics announced that efdamrofusp alfa met the phase 3 primary endpoint, showing noninferior vision gains compared to aflibercept
  • Efdamrofusp alfa therapy allowed an extended dosing interval
  • The incidence of macular atrophy was lower in the efdamrofusp alfa group compared to the aflibercept group

Innovent Biologics announced that its phase 3 clinical study (STAR) of efdamrofusp alfa injection in the Chinese patients with neovascular AMD met the 52-week primary endpoint. Efdamrofusp alfa demonstrated noninferiority to aflibercept in vision improvement while also showing the clinical advantage of extended 16-week dosing intervals and the potential to reduce the risk of macular atrophy (MA).

The study enrolled a total of 600 participants (including 65% treatment-naïve participants) with a baseline mean BCVA of 58.1 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and a baseline mean central subfield thickness of 420.75 μm. Participants were randomly assigned in a 1:1 ratio to receive either efdamrofusp alfa 8 mg or aflibercept 2 mg. Both groups received three loading doses administered every 4 weeks. After the completion of the loading doses, the efdamrofusp alfa group was treated at 16-, 12-, or 8-week intervals based on the disease activity assessments at weeks 16 and 20. The aflibercept group completed the subsequent treatment at 8-week intervals.

The study duration was 100 weeks, and the primary endpoint was the change from baseline in the study eye’s BCVA at week 52. The randomization stratification factors in this study were the presence or absence of type 2 choroidal neovascularization on OCT in the study eye and whether the study eye had previously received anti-VEGF treatment.

At week 52, the least squares mean estimate of the mean BCVA change from baseline in the efdamrofusp alfa and aflibercept groups was 10.37 (0.547) and 10.11 (0.545) ETDRS letters, respectively.

Approximately 86% of the efdamrofusp alfa group achieved a dosing interval of every 12 weeks or above during the maintenance period; 72.8% of participants achieved a dosing interval of every 16 weeks. At week 52, approximately 95% of the participants receiving doses every 12/16 weeks maintained their interval without requiring retreatment. Furthermore, 56.3% of the participants showed no disease activity at week 24, demonstrating the potential to extend the dosing interval to every 20 weeks.

The proportion of participants with no intraretinal fluid and no subretinal fluid in the fovea at week 16 was comparable between the two groups, and the improvements from baseline in the change in central subfield thickness from baseline and other anatomic endpoints were similar at week 52.

Additionally, at week 52, the incidence of MA in the efdamrofusp alfa and aflibercept groups was 1.5% and 2.9%, respectively. The incidence of MA was 50% lower in the efdamrofusp alfa compared to the aflibercept group, and the trend was reportedly consistent with the results of phase 2 studies, suggesting that efdamrofusp alfa might have the potential to inhibit MA.

The overall incidence of adverse events was comparable between groups. Most ocular adverse events were mild to moderate and resolved after observation or routine management.

The follow-up of this study is still ongoing.