공고 • Oct 27
Apellis Pharmaceuticals, Inc. Presents Positive Results from the Phase 3 VALIANT Study at Kidney Week
Apellis Pharmaceuticals, Inc. announced that positive results from the Phase 3 VALIANT study were presented as an oral presentation during the High-Impact Clinical Trials session at the American Society of Nephrology (ASN) Kidney Week. The results highlighted the strength of systemic pegcetacoplan treatment in patients with C3 glomerulopathy (C3G) and primary immune complex membranoproliferative glomerulonephritis (IC-MPGN), which are rare, debilitating kidney diseases. Statistically significant 68% proteinuria reduction across a broad study population, with reduction observed as early as Week 4: Pegcetacoplan-treated patients showed a statistically significant and clinically meaningful 68.1% (p<0.0001) proteinuria reduction (log-transformed ratio of urine protein-to-creatinine ratio) compared to placebo, both in addition to standard of care therapy, at Week 26. The proteinuria reduction was observed as early as Week 4 and continued through the six-month treatment period. Proteinuria reduction was consistent across broad patient subgroups including adolescent and adult patients, C3G and IC-MPGN patients, and patients with native and post-transplant kidneys. Pegcetacoplan stabilized eGFR and demonstrated substantial reduction in C3c staining: Patients treated with pegcetacoplan achieved stabilization of estimated glomerular filtration rate (eGFR), a key measure of kidney function, with a difference of +6.3mL/min/1.73m2 (nominal p value=0.03) over six months compared to placebo. Additionally, a substantial proportion of patients treated with pegcetacoplan demonstrated a reduction in C3c staining intensity. Excessive C3c deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure. 74.3% of patients in the pegcetacoplan group and 11.8% on placebo achieved a reduction in C3c staining intensity by two or more orders of magnitude from baseline, resulting in 27-fold higher odds of achieving this reduction with pegcetacoplan (nominal p value <0.0001). 71.4% of pegcetacoplan-treated patients achieved zero C3c staining intensity, demonstrating complete clearance of C3c deposits. All secondary endpoints favored treatment with pegcetacoplan: In addition to the positive results on proteinuria, eGFR, and C3c staining, pegcetacoplan demonstrated statistical significance on the key secondary endpoints of composite renal endpoint, which combines proteinuria reduction and eGFR stabilization, and proteinuria reduction of at least 50% compared to baseline, as well as a numerical improvement in the C3G histologic index activity score. During the randomized, controlled 26-week treatment period, pegcetacoplan demonstrated favorable safety and tolerability, as well as a high compliance rate, consistent with its established profile. Rates of treatment-emergent adverse events (AEs) (84.1% in pegcetacoplan vs. 93.4% in placebo), serious AEs (9.5% vs. 9.8%), severe AEs (4.8 % vs. 6.6%), and AEs leading to study discontinuation (1.6% vs. 1.6%) were similar between the pegcetacoplan and placebo groups. There were no cases of meningococcal meningitis or serious infections attributed to encapsulated bacteria. All patients who have already completed the VALIANT study have now enrolled into the VALE long-term extension study. Apellis plans to submit a supplemental new drug application to the U.S. Food and Drug Administration in early 2025. Sobi plans to submit a marketing application with the European Medicines Agency in 2025. About the VALIANT Study: The VALIANT Phase 3 study is a randomized, placebo-controlled, double-blinded, multi-center study designed to evaluate pegcetacoplan efficacy and safety in 124 patients who are 12 years of age and older with C3G or primary IC-MPGN. It is the larger single trial conducted in these populations and the only study to include adolescent and adult patients, with native and post-transplant kidneys. Study participants were randomized to receive pegcetacoplan or placebo twice weekly for 26 weeks. Following this 26-week randomized controlled period, patients are able to proceed to a 26-week open-label phase in which all patients receive pegcetacoplan. The primary endpoint of the study was the log transformed ratio of urine protein-to-creatinine ratio (uPCR) at Week 26 compared to baseline. About C3 Glomerulopathy (C3G) and Primary Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN): C3G and primary IC-MPGN are rare and debilitating kidney diseases that can lead to kidney failure. Excessive C3c deposits are a key marker of disease activity, which can lead to kidney inflammation, damage, and failure. There are no treatments that target the underlying cause of these diseases. Approximately 50% of people living with C3G and IC-MPGN suffer from kidney failure within five to 10 years of diagnosis, requiring a burdensome kidney transplant or lifelong dialysis. Additionally, 90% of patients who previously received a kidney transplant will experience disease recurrence. The diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe. Pegcetacoplan is a targeted C3 therapy designed to regulate excessive activation of the complement cascade, a part of the body’s immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is under investigation for rare diseases across hematology and nephrology. Pegcetacoplan is approved for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) as EMPAVELI®/Aspaveli® in the United States, European Union, and other countries globally. Apellis and Sobi have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialization rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialization rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy.
