Apellis Pharmaceuticals (APLS) Status Update summary

Study design and patient population

• VALIANT was a double-blind, randomized, placebo-controlled phase III trial evaluating pegcetacoplan in C3G and IC-MPGN patients aged ≥12 years, including both native and post-transplant cases, with both groups on optimized standard of care.

• Patients received pegcetacoplan or placebo (up to 1080 mg subcutaneously twice weekly) for 26 weeks; primary and secondary endpoints were assessed at 26 weeks.

• Inclusion required active disease, proteinuria ≥1g/day, and eGFR ≥30 mL/min/1.73 m²; patients with significant glomerular sclerosis, transplant rejection, or recent severe infection were excluded.

• Majority of patients had C3G, with some IC-MPGN and post-transplant recurrence cases.

Efficacy results

• Pegcetacoplan achieved a 68.1% reduction in proteinuria at 26 weeks versus placebo (P<.0001), with significant effects seen as early as week 4 and consistent across age, disease type, and transplant status.

• 60.3% of pegcetacoplan-treated patients achieved ≥50% proteinuria reduction compared to 4.9% with placebo, and 50.8% achieved proteinuria <1g/g at week 26; nephrotic-range proteinuria dropped from 38% to 14%.

• Pegcetacoplan stabilized eGFR (+6.3 mL/min/1.73 m² vs placebo, P=.03 nominal), with 49.2% achieving a composite endpoint of ≥50% proteinuria reduction and ≤15% eGFR decline (vs 3.3% placebo, 27x higher odds, P<.0001).

• 71% of patients had zero C3c staining on biopsy at week 26, compared to 11.8% with placebo (27x higher odds, P<.0001), indicating effective disease control.

Biomarker and histology findings

• Pegcetacoplan reduced the activity score of the C3G histologic index, though the difference versus placebo was not statistically significant (P=.28).

• The C3c staining endpoint is considered highly meaningful by clinicians, indicating disease shutdown.