Apellis Pharmaceuticals (APLS) Study Result summary

Study design and patient population

• Phase 3 VALIANT study enrolled 124 patients aged 12 and older with C3G or primary IC-MPGN, including both native and post-transplant kidney patients, in a randomized, double-blind, placebo-controlled, multi-center trial.

• Patients received pegcetacoplan or placebo plus standard of care for 26 weeks, followed by an open-label extension.

• The primary endpoint was the log-transformed urine protein-to-creatinine ratio (UPCR) at week 26 compared to baseline.

• Secondary endpoints included change in eGFR, reduction in C3 staining, and composite renal endpoints.

• Patient demographics were similar between treatment arms, with an average age of 26 years.

Efficacy results

• Pegcetacoplan achieved a 68% reduction in proteinuria versus placebo at week 26 (p<0.0001), with effects seen within four weeks and sustained through 26 weeks.

• Consistent efficacy was observed across all subgroups: C3G, IC-MPGN, adolescents, adults, native kidneys, and transplant patients.

• Statistically significant improvements were seen in key secondary endpoints, including composite renal endpoint and ≥50% proteinuria reduction.

• Nominally significant improvements were seen in C3c staining and eGFR stabilization.

• Pegcetacoplan showed rapid and sustained stabilization of eGFR, with all secondary endpoints favoring treatment.

Safety and tolerability

• Pegcetacoplan was well tolerated, with low and similar rates of adverse events, serious adverse events, and discontinuations compared to placebo.

• No cases of meningitis or serious infections due to encapsulated bacteria were reported.

• All patients completing the study enrolled in the VALE long-term extension study.