APLS Apellis Pharmaceuticals Inc

Apellis Pharmaceuticals, Inc. (Nasdaq: APLS) and Sobi® today 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.

“These unprecedented results represent a potential breakthrough for patients living with C3G and IC-MPGN. Pegcetacoplan is the only treatment to achieve substantial and clinically meaningful effects across all key markers of disease: proteinuria, eGFR stabilization, and C3c staining,” said Carla Nester, M.D., MSA, FASN, lead principal investigator for the VALIANT study, professor of internal medicine and pediatrics, and director of pediatric nephrology, University of Iowa Stead Family Children's Hospital. “C3G and IC-MPGN affect patients as early as adolescence, often leading to either a kidney transplant or lifelong dialysis, so there is an urgent need for an approved treatment that can prolong kidney function.”

Statistically significant 68% proteinuria reduction across a broad study population, with reduction observed as early as Week 4Pegcetacoplan-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.

“In the largest pivotal study in C3G and IC-MPGN, pegcetacoplan rapidly, significantly, and consistently improved key outcomes for patients with C3G and IC-MPGN,” said Peter Hillmen, M.B., Ch.B., Ph.D., chief medical advisor, rare, Apellis. “We are thrilled by these results, which underscore the potential for pegcetacoplan to significantly improve patients’ lives by directly targeting C3, the underlying cause of C3G and IC-MPGN.”

All secondary endpoints favored treatment with pegcetacoplanIn 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 StudyThe VALIANT Phase 3 study (NCT05067127) 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 largest 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.1 Additionally, 90% of patients who previously received a kidney transplant will experience disease recurrence.2 The diseases are estimated to affect 5,000 people in the United States and up to 8,000 in Europe.3 

About Pegcetacoplan in Rare DiseasesPegcetacoplan 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.

About the Apellis and Sobi CollaborationApellis 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.

About ApellisApellis Pharmaceuticals, Inc. is a global biopharmaceutical company that combines courageous science and compassion to develop life-changing therapies for some of the most challenging diseases patients face. We ushered in the first new class of complement medicine in 15 years and now have two approved medicines targeting C3. These include the first-ever therapy for geographic atrophy, a leading cause of blindness around the world. We believe we have only begun to unlock the potential of targeting C3 across serious retinal, rare, and neurological diseases. For more information, please visit http://apellis.com or follow us on X (Twitter) and LinkedIn.

Apellis Forward-Looking Statement Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements regarding plans to submit applications for regulatory approval for the treatment of patients with C3G and IC-MPGN. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including whether systemic pegcetacoplan will receive approval for those indications from the FDA or equivalent foreign regulatory agencies when expected or at all; and any other factors discussed in the “Risk Factors” section of Apellis’ Annual Report on Form 10-K with the Securities and Exchange Commission on February 27, 2024 and the risks described in other filings that Apellis may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Apellis specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.Media:Tracy Vineismedia@apellis.com 617-420-4839

Investors: Meredith Kaya meredith.kaya@apellis.com617.599.8178

References

1. C3 glomerulopathy. National Institute of Health, Genetics Home Reference. https://ghr.nlm.nih.gov/condition/c3-glomerulopathy#resources. Accessed November 21, 2019. 2. Tarragón, B, et al. C3 Glomerulopathy Recurs Early after Kidney Transplantation in Serial Biopsies Performed within the First 2 Years after Transplantation. Clinical Journal of the American Society of Nephrology. August 2024; 19(8)1005-1015. doi: 10.2215/CJN.0000000000000474.3. Data on file using literature consensus.