- |||||||||| Empaveli (pegcetacoplan SC) / Apellis, SOBI
Journal: Trial of Pegcetacoplan in C3 Glomerulopathy and Immune-Complex MPGN. (Pubmed Central) - Dec 3, 2025
P3
Pegcetacoplan resulted in a significantly greater reduction in proteinuria than placebo among patients with C3 glomerulopathy or primary immune-complex MPGN. (Funded by Apellis Pharmaceuticals and Sobi [Swedish Orphan Biovitrum]; VALIANT ClinicalTrials.gov number, NCT05067127.).
- |||||||||| Fabhalta (iptacopan) / Novartis, Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Review, Journal: Novel treatment strategies for C3 glomerulopathy: complement blockade. (Pubmed Central) - Dec 3, 2025
Notably, use of both agents was recently approved by the United States Food and Drug Administration. Herein we review novel treatment strategies for patients suffering from C3G with a focus on agents targeting complement system.
- |||||||||| Syfovre (pegcetacoplan intravitreal) / Apellis
Journal: Geographic Atrophy Progression in Clinical Practice Before and After Pegcetacoplan Treatment. (Pubmed Central) - Nov 24, 2025
This retrospective study evaluated changes in ocular characteristics and retinal pigment epithelium (RPE) and photoreceptor ellipsoid zone (EZ) depletion rates before and after intravitreal pegcetacoplan initiation in clinical practice...These real-world findings align with data from the pegcetacoplan phase 3 trials, showing reduced RPE and EZ depletion rates without changes in rates of BRVA loss. Additional studies are warranted.
- |||||||||| Review, Journal: Advances in Complement Inhibition Therapies for Paroxysmal Nocturnal Hemoglobinuria and Autoimmune Hemolytic Disorders. (Pubmed Central) - Nov 19, 2025
The terminal complement inhibitor, eculizumab, was the initial drug available which significantly reduced hemolysis and thrombotic events but failed to resolve residual extravascular hemolysis and transfusion requirements...This review highlights the evolving therapeutic landscape in complement inhibition by summarizing clinical evidence for the terminal complement inhibitors, as well as pegcetacoplan, iptacopan, and danicopan as emerging agents for treatment of PNH and autoimmune hemolytic anemias-warm AIHA and cold agglutinin disease (CAD). The review also examines ongoing clinical trials and proposes future directions to optimize therapeutic outcomes to address remaining clinical challenges.
- |||||||||| Syfovre (pegcetacoplan intravitreal) / Apellis
Journal: Short-Term Changes in Intraocular Pressure Following Intravitreal Injection of Pegcetacoplan. (Pubmed Central) - Nov 17, 2025
To determine short-term changes in intraocular pressure (IOP) after intravitreal injection of 0.1 mL pegcetacoplan (Syfovre; Apellis Pharmaceuticals) for the treatment of geographic atrophy (GA)...Following pegcetacoplan injections, immediate IOP elevation was observed, which gradually declined within the first 30 minutes. Eyes with higher baseline IOP or a history of glaucoma exhibited higher postinjection IOP.
- |||||||||| Empaveli (pegcetacoplan SC) / Apellis, SOBI
Early response in complement inhibitor na (M / N (Confex)) - Nov 5, 2025 - Abstract #DGHO2025DGHO_1598;
P3
Pts benefited from immediate and sustained improvements in key hematological parameters, including those required to enable symptom improvement (Hb) and demonstrate control of hemolysis (LDH).In escape pts experiencing a Hb drop ?2 g/dL before PEG initiation, PEG led to rapid hemolysis control in most pts. These results provide further evidence to support PEG use in first-line treatment of adult PNH pts.
- |||||||||| Empaveli (pegcetacoplan SC) / Apellis, SOBI
Benefit of pegcetacoplan in patients with paroxysmal nocturnal hemoglobinuria irrespective of baseline transfusion status in Long-term Follow-up (S / T (Confex)) - Nov 5, 2025 - Abstract #DGHO2025DGHO_1061;
After 6 months on PEG, pts experienced significant improvements in hematologic parameters, which were sustained at 12 months. Background: Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by complement-mediated hemolysis, resulting in increased thrombosis risk and substantial symptom burden.There is an ongoing need to further understand the relevance of baseline characteristics, as predictors of treatment response, to guide decision making.Pegcetacoplan (PEG) is a complement C3/C3b inhibitor, providing efficient control of intravascular and extravascular hemolysis in PNH patients.The effect of baseline transfusion status on key hematological and clinical responses to PEG in C5i-experienced and -na
- |||||||||| Soliris (eculizumab) / AstraZeneca, Ultomiris (ravulizumab-cwvz) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Pegcetacoplan for patients with transplant-associated thrombotic microangiopathy treatment: A real-world report of six cases (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_6590;
Treatment wasassociated with rapid and complete remissions, including in patients refractory to C5 inhibitors and otherconventional therapies. These encouraging findings support the investigation of pegcetacoplan inprospective clinical trials to formally establish its role in the management of this severe HSCTcomplication.
- |||||||||| Navigating the complement cascade: A multicenter journey from pegcetacoplan to iptacopan in paroxysmal nocturnal hemoglobinuria (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_2966;
The highacceptance rate suggests that patients prefer oral therapy over subcutaneous administration. Thesefindings address a critical knowledge gap in proximal complement inhibitor sequencing, suggesting thatiptacopan is an effective therapeutic option for patients with inadequate pegcetacoplan response andsupporting the development of evidence-based treatment algorithms for optimal PNH care in the era ofmultiple complement inhibitor options.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Management of a real-world cohort of patients with paroxysmal nocturnal hemoglobinuria treated with iptacopan: A multi-institutional analysis (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_2963;
In this real-world cohort, iptacopan provided substantial and durable hemoglobinimprovement across naive and previously treated patients with PNH, with meaningful reduction inhemolytic parameters, absence of thrombosis, and low BTH rate predominantly linked to infection.Patients with previous satisfactory responses also showed improved Hgb levels. The favorable safetyprofile and high treatment persistence underscore iptacopan's role as an effective first-line or switchtherapy and support its incorporation into evidence-based sequencing algorithms in the evolving PNHtreatment landscape.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Real-world use of oral iptacopan monotherapy in paroxysmal nocturnal hemoglobinuria (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_2960;
3 patients received additional doses of eculizumab, and 3 patients were permanently switched toalternative CI.Infections requiring antibiotics occurred in 21 patients (14.1%), most commonly respiratory source (9/21).8 patients required hospitalization (urinary tract infection (n=2), chest infection (n=4), cellulitis (n=1)unknown (n=1)), 3 with BTH...No thrombotic eventsoccurred. These findings support the effectiveness of iptacopan in the treatment of PNH.
- |||||||||| Soliris (eculizumab) / AstraZeneca
Iron overload and iron chelation therapy in PNH patients on complement inhibitors: A single centre experience. (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_2952;
In ourseries, a third of patients under iC5 treatment required iron chelation therapy, due to moderate liver ironoverload, with a median duration of 2 years and adequate response measured by liver MRi. 3 out of 4patients were able to discontinue iron chelation therapy after switching to proximal complementinhibition and controlling EVH.
- |||||||||| Empaveli (pegcetacoplan SC) / Apellis, SOBI
Complement inhibitor use is not a significant predictor of cancer incidence: A real-world study of patients requiring chronic complement blockade. (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_2525;
Sixwere treated with eculizumab and ravulizumab, 4 with eculizumab alone, 1 with ravulizumab alone, and 1with eculizumab, ravulizumab, pegcetacoplan, and iptacopan at various points...Factors such asfamily history, smoking/alcohol use, and past medical history of HPV, hepatitis B, hepatitis C, and HIVremain established predictors for cancer incidence. Further analysis in a larger cohort is needed tovalidate these initial results.
- |||||||||| Empaveli (pegcetacoplan SC) / Apellis, SOBI
Comparative efficacy of complement inhibitors in complement Inhibitor (OCCC - West Halls B3-B4) - Nov 4, 2025 - Abstract #ASH2025ASH_2442;
A frequentist model network meta-analyses were conducted in RStudio (v5.4.1) using acommon-effects model. A total of 4 randomized controlled trials evaluating 4 complement inhibitor agents (Ravulizumab,Crovalimab, Eculizumab & Pegcetacoplan) were included in this meta-analysis, involving 589 complementinhibitor
- |||||||||| Syfovre (pegcetacoplan intravitreal) / Apellis, Izervay (avacincaptad pegol intravitreal solution) / Astellas
Journal: Efficacy of Intravitreal Pegcetacoplan vs Avacincaptad Pegol in Patients With Geographic Atrophy. (Pubmed Central) - Oct 20, 2025
P3
A numerically greater reduction in GA lesion growth was observed with pegcetacoplan every other month vs avacincaptad pegol monthly (95% CI, -1.130 to -0.300; P?=?.25). Matching-adjusted indirect comparisons support a greater reduction in GA growth with pegcetacoplan monthly vs avacincaptad pegol monthly and no significant difference between pegcetacoplan every other month and avacincaptad pegol monthly.
- |||||||||| Empaveli (pegcetacoplan SC) / Apellis, SOBI
Pegcetacoplan Subcutaneous Infusion: Early Access and Patient Training (Exhibit Hall, Convention Center) - Oct 18, 2025 - Abstract #KIDNEYWEEK2025KIDNEY_WEEK_4298;
There were no reported difficulties or adverse events related to the SCI administration or adverse effects with pegcetacoplan Conclusion Patients can safely self-administered SCI infusions of pegcetacoplan with minimal training. One in-person training session was sufficient to make patients competent in self-administration and remote training was also successfully used.
- |||||||||| Fabhalta (iptacopan) / Novartis, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Clinical Efficacy of Pegcetacoplan vs. Iptacopan in Patients with C3 Glomerulopathy: Indirect Treatment Comparisons (Exhibit Hall, Convention Center) - Oct 18, 2025 - Abstract #KIDNEYWEEK2025KIDNEY_WEEK_4230;
P3
Conclusion These two ITCs indicate that pegcetacoplan was superior to iptacopan in lowering proteinuria levels and achieving the composite renal endpoint in patients with C3G. The findings from this analysis may help guide clinicians managing patients with this rare condition.
- |||||||||| APL-3007 / Apellis, Syfovre (pegcetacoplan intravitreal) / Apellis
New P2 trial: A Phase 2, Randomized, Placebo Controlled, Multicenter, Masked Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacodynamics of Multidose APL 3007 in Combination With Syfovre/Pegcetacoplan (APL-2) in Patients Diagnosed With Geographic Atrophy Secondary to Age Related Macular Degeneratio (clinicaltrials.gov) - Oct 16, 2025
P2, N=240, Recruiting,
- |||||||||| Review, Journal: Progress in the use of biological therapies to treat paroxysmal nocturnal hemoglobinuria: focus on patient profiling. (Pubmed Central) - Oct 13, 2025
Proximal complement inhibitors, including the small molecule pegcetacoplan (C3 inhibitor), the recently approved orally administered iptacopan (factor B inhibitor), and danicopan (factor D inhibitor, in combination with anti-C5), efficiently control C3-mediated extravascular hemolysis...PNH specialists must now balance multiple factors beyond efficacy alone. Disease characteristics such as previous thrombotic events or transfusion needs, as well as drug administration routes, patient preferences toward oral or parenteral administration and expected compliance, will all influence clinical decisions.
- |||||||||| Soliris (eculizumab) / AstraZeneca, Empaveli (pegcetacoplan SC) / Apellis, SOBI
Journal: Higher Doses of Eculizumab may be Beneficial in Paroxysmal Nocturnal Haemoglobinuria in Pregnancy. (Pubmed Central) - Oct 9, 2025
Disease characteristics such as previous thrombotic events or transfusion needs, as well as drug administration routes, patient preferences toward oral or parenteral administration and expected compliance, will all influence clinical decisions. Pregnant patients with classical paroxysmal nocturnal haemoglobinuria need individualised treatment and frequent monitoring.Even with appropriate terminal complement blockade, pregnant patients may have significant breakthrough haemolysis burden, likely due to C3b mediated opsonisation.Higher than standard doses of eculizumab may help control breakthrough haemolysis in pregnant patients.
- |||||||||| Review, Journal: Pharmacological Therapies in Paroxysmal Nocturnal Haemoglobinuria: Focus on Complement Inhibition. (Pubmed Central) - Sep 23, 2025
This has been largely supplanted by a longer-acting antibody, ravulizumab, targeting the same binding site on C5...Other terminal inhibitors available include eculizumab biosimilars, crovalimab, pozelimab and cemdisiran (combination)...Currently available proximal inhibitors (and their targets) are pegcetacoplan (C3), danicopan (Factor D) and iptacopan (Factor B). While effective, as with all other complement inhibitors, there is a risk of breakthrough IVH with their use and approaches to manage this complication are being developed.
- |||||||||| Review, Journal: New treatment strategies for paroxysmal nocturnal hemoglobinuria: drug selection in the era of novel complement inhibitors (Pubmed Central) - Sep 4, 2025
Danicopan (factor D inhibitor) and ipracopan (factor B inhibitor) also improve anemia and fatigue...In addition, long-term real-world infection data remain necessary. While IVH control has improved PNH prognosis, future therapies should focus on patients with persistent anemia or insufficient improvement in quality of life, and should aim to enhance hemoglobin levels and overall well-being while managing BTH for optimal care.
|
