Aspaveli (pegcetacoplan) has demonstrated sustained efficacy in treating two rare and devastating kidney diseases, achieving a statistically significant 68% reduction in proteinuria compared to placebo at Week 26 that was maintained through one year, according to new data from the Phase 3 VALIANT study presented at the European Renal Association Congress.
The results represent a potential breakthrough for patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), conditions that currently have no approved treatments and lead to kidney failure in approximately 50% of patients within 5-10 years of diagnosis.
Robust Efficacy Across Patient Populations
The VALIANT study, the largest single trial conducted in these patient populations, enrolled 124 patients aged 12 years and older with C3G or primary IC-MPGN. The drug's efficacy was consistent across multiple subgroups, including patients with C3G, IC-MPGN, adolescents, adults, and those with transplanted kidneys.
"The one-year Phase 3 results are very compelling, confirming Aspaveli's sustained benefits across key markers of disease," said Fadi Fakhouri, M.D., PhD, presenting author and co-lead principal investigator for the VALIANT study. "Given the high risk of kidney failure, treatment efficacy is incredibly important to C3G and primary IC-MPGN patients, many of whom are in the prime of their lives."
Beyond the primary endpoint of proteinuria reduction, Aspaveli achieved statistically significant improvement in a composite renal endpoint, demonstrating both proteinuria reduction and kidney function stabilization as measured by estimated glomerular filtration rate (eGFR).
Favorable Safety Profile
The drug showed a clean safety profile with no cases of meningitis or infections from encapsulated bacteria, addressing a critical concern with other complement inhibitors. Adverse events were comparable to placebo, with no new safety signals identified during the one-year study period.
"These data reinforce the strength of the EMPAVELI efficacy and safety profile across a broad population of patients with C3G and primary IC-MPGN, including adults and adolescents with native and post-transplant kidney disease," said Peter Hillmen, M.B., Ch.B., Ph.D., chief medical advisor for rare disease at Apellis.
Addressing Significant Unmet Medical Need
C3G and primary IC-MPGN are rare but debilitating kidney diseases characterized by excessive C3 deposits that lead to kidney inflammation, damage, and failure. The diseases are estimated to affect approximately 5,000 people in the United States and up to 8,000 in Europe, with a combined total of roughly 15,500 diagnosed patients across the seven major markets.
Current treatment relies on off-label use of immunosuppressants and RAAS inhibitors, which offer limited efficacy and tolerability. Approximately 90% of patients who receive kidney transplants experience disease recurrence, highlighting the urgent need for effective therapies.
Regulatory Timeline and Market Potential
Sobi and Apellis plan to submit regulatory applications in 2025, with Apellis handling U.S. submissions and Sobi leading efforts in Europe and Japan. An FDA decision is expected by summer 2025.
"With an FDA decision this summer, we look forward to bringing EMPAVELI to patients living with these rare and severe kidney diseases as quickly as possible," said Hillmen.
The collaboration leverages each company's strengths, with Apellis providing clinical expertise and Sobi offering global commercial scale through its established nephrology salesforce. Aspaveli is already approved for paroxysmal nocturnal hemoglobinuria (PNH) in the United States, European Union, and other countries globally.
Mechanism of Action
Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, a part of the body's immune system that can lead to the onset and progression of serious diseases. By targeting the complement cascade at its root, the drug halts the relentless kidney damage caused by uncontrolled inflammation.
The VALIANT study included a 26-week randomized controlled period followed by a 26-week open-label phase. Patients who switched from placebo to Aspaveli at the start of the open-label period demonstrated a similar magnitude of benefit in proteinuria reduction and stabilization of kidney function.
