Sozinibercept Combination Therapy Exhibits Durability for nAMD, DME

Nathan C. Steinle, MD

Credit: California Retina Consultants

Intravitreal dosing of sozinibercept (OPT-302), an anti-VEGF-C/D ‘trap’, in combination with anti-VEGF-A therapy, was well-tolerated and effective for patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).

These data, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, showed intravitreal dosing of sozinibercept supported every 8 weeks (Q8W) dosing or longer, after the loading dose, in combination with ranibizumab or aflibercept therapy.

“Sozinibercept is a VEGF-C/D inhibitor and we’re looking for superior visual gains for our patients, rather than just anti-VEGF-A inhibition alone,” said presenting investigator Nathan C. Steinle, MD, California Retina Consultants. “We know, in the eye, it behaves very similarly to aflibercept and we know it has a very similar safety profile to what we’ve seen with our anti-VEGF therapy.”

VEGF-A inhibition can elevate VEGF-C and VEGF-D, which can contribute to sub-optimal clinical efficacy of anti-VEGF-A treatments. In combination with any VEGF-A inhibitor, sozinibercept completely blocks VEGFR-2 and VEGFR-3 signaling, inhibiting critical pathways driving angiogenesis and vascular leakage.

Monthly dosing of sozinibercept in combination with standard-of-care anti-VEGF-A therapy has demonstrated promising efficacy for nAMD and DME in clinical studies. In the current analysis, Steinle and the investigative team evaluated safety and durability through 6 months after 3 monthly loading doses.

A total of 40 patients with nAMD (n = 31) or DME (n = 9) were assessed in a prospective, post-hoc analysis from two Phase 1b, open-label, dose-escalation studies. Treatment-naive or prior-treated patients with nAMD were provided 3 intravitreal injections of ranibizumab 0.5 mg in combination with sozinibercept 0.3 mg (n = 5) or 1 mg (n =5), or aflibercept 2 mg plus sozinibercept 0.3 mg (n = 3), 1 mg (n = 3), or 2 mg (n = 3).

All patients were followed through 2 to 6 months, in which pro re nata (PRN) treatment with anti-VEGF-A therapy was based on worsening disease activity or investigator discretion. Worsening disease activity was defined as a ≥10% increase in central subfield thickness (CST) or a ≥5-letter decline in best-corrected visual acuity (BCVA) from Month 2.

Upon analysis, Steinle and colleagues found the combination therapy with sozinibercept was well-tolerated without dose-limiting toxicities.

Treatment-naive patients (n = 14) with nAMD demonstrated a mean BCVA, including the gain from baseline, for soznibercept plus ranibizumab of 56.4, 67.2, and 65.6 letters at Months 0, 3, and 6. The equivalent mean BCVA for those previously treated with anti-VEGF-A therapy (n = 17) was 64.5, 68.9, and 66.8 letters, respectively.

Moreover, the mean time to first retreatment of PRN anti-VEGF-A therapy in Months 2 to 6 was 60.4 days, with a mean of 1.4 injections, in treatment-naive patients with nAMD. For treatment-experienced patients with nAMD, the rates were 50.7 days and 1.9 injections, respectively.

Among treatment-experienced patients with persistent DME, the mean BCVA, including gains from baseline, after switching to soznibercept plus aflibercept, was 65, 72.7, and 69 letters at Months 0, 3, and 6, respectively. Patients experienced a mean duration of 79.6 days to receive PRN anti-VEGF-A retreatment and a mean number of 0.4 injections during Months 2 to 6.

In his presentation, Steinle announced the two Phase 3 trials investigating sozinibercept for nAMD, COAST and ShORe, have completed enrollment, with a primary efficacy endpoint of visual acuity change at Week 52 to support Biologics License Application (BLA) submission, and safety follow-up through Week 100.

COAST will evaluate sozinibercept in combination with aflibercept for 998 patients with treatment-naive nAMD, and ShORe will assess sozinibercept in combination with ranibizumab for 986 patients with treatment-naive nAMD, with 4- or 8-week dosing in both trials.

“Both ShORe and COAST are now fully enrolled, with about 1000 patients in both, and we look forward to the results in early-to-mid-2025,” Steinle added.

Reference

_{Steinle N. Durability of Combination Therapy of Sozinibercept, an Anti-VEGF-C/D "Trap" With Ranibizumab in nAMD or Aflibercept in DME. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}