Empaveli (pegcetacoplan SC) / Apellis, SOBI - LARVOL DELTA

Efficacy of Pegcetacoplan in Children with C3 Glomerulopathy (KIDNEY WEEK 2024) - "The Full Poster will be available Saturday, October 26, 2024 at 10:00:00 AM US/Pacific.. Abstract will be available Friday, October 11, 2024 at 6:00:00 AM US/Pacific."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis

Long-Term Safety and Efficacy of Pegcetacoplan in Patients with C3 Glomerulopathy or Primary Immune-Complex Membranoproliferative Glomerulonephritis: The Long-Term VALE Extension Study (KIDNEY WEEK 2024) - "The Full Poster will be available Saturday, October 26, 2024 at 10:00:00 AM US/Pacific.. Abstract will be available Friday, October 11, 2024 at 6:00:00 AM US/Pacific."

Clinical • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology

Pegcetacoplan for Post-transplant Recurrent C3 Glomerulopathy (C3G) or Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN) in NOBLE: 52-Week Patient Evolution (KIDNEY WEEK 2024) - "The Full Poster will be available Saturday, October 26, 2024 at 10:00:00 AM US/Pacific.. Abstract will be available Friday, October 11, 2024 at 6:00:00 AM US/Pacific."

Clinical • Post-transplantation • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Transplantation

Iptacopan (Fabhalta) for paroxysmal nocturnal hemoglobinuria. (PubMed, Med Lett Drugs Ther) - No abstract available

Journal • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

A Study to Evaluate the Efficacy and Safety of Pegcetacoplan in Patients With Cold Agglutinin Disease (CAD) (clinicaltrials.gov) - P3 | N=24 | Completed | Sponsor: Swedish Orphan Biovitrum | Suspended ➔ Completed | N=57 ➔ 24 | Trial primary completion date: Oct 2024 ➔ May 2024

Enrollment change • Trial completion • Trial primary completion date • Autoimmune Hemolytic Anemia • Complement-mediated Rare Disorders • Hematological Disorders

Efficacy of pegcetacoplan in children with C3 glomerulopathy (ESPN 2024) - "All our patients showed a rapid over-normalization of the C3 levels, a significant reduction of proteinuria and a significant increase in albuminemia. We think that the present case series, although small and with a short follow up period, may be important to support other physicians to consider this treatment as an opportunity for their C3G patients."

Clinical • Chronic Kidney Disease • Complement-mediated Rare Disorders • Glomerulonephritis • Inflammation • Nephrology • Pediatrics • Renal Disease

Pegcetacoplan for paediatric patients with C3 glomerulopathy or Immune complex mediated membranoproliferative glomerulonephritis: Phase 3 VALIANT Study (ESPN 2024) - P2, P3 | "The phase 3 VALIANT study will investigate the efficacy and safety of pegcetacoplan in adults and adolescents with C3G or primary IC-MPGN in either native kidney disease or as a post-transplant recurrence."

Clinical • P3 data • Acute Kidney Injury • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease

Pegcetacoplan for the treatment of pediatric complement 3 glomerulonephritis: a case report (ESPN 2024) - "Despite treatment with high dose of prednisone 40 mg/day and mycophenolate mofetil 500 mg twice daily for immunosuppression and amlodipine, lisinopril, hydrochlorothiazide, and fluid restriction for difficult-to-manage edema, he continued to have nephrotic range proteinuria, with a urine protein-to-creatinine ratio (uPCR) of 10 g/g, a serum creatinine of 0.4 mg/dL, a low serum C3 level (35 mg/dL), and anasarca. In this pediatric patient, compassionate use of pegcetacoplan was associated with rapid clinical improvement without adverse effects, and clinical effectiveness was confirmed by laboratory and histologic results within 6 months of treatment initiation."

Case report • Clinical • Acute Kidney Injury • Complement-mediated Rare Disorders • Glomerulonephritis • Lupus Nephritis • Nephrology • Pediatrics • Renal Disease

Navigating the Complement Pathway to Optimize PNH Treatment with Pegcetacoplan and Other Currently Approved Complement Inhibitors. (PubMed, Int J Mol Sci) - "State-of-the-art PNH treatments act by inhibiting the dysregulated complement at distinct points in the activation pathway: late at the C5 level (C5 inhibitors, eculizumab, ravulizumab, and crovalimab), centrally at the C3 level (C3/C3b inhibitors and pegcetacoplan), and early at the initiation and amplification of the alternative pathway (factor B inhibitor, iptacopan; factor D inhibitor, danicopan). Through their differing mechanisms of action, these treatments elicit varying profiles of disease control and offer valuable insights into the molecular underpinnings of PNH. This narrative review provides an overview of the mechanisms of action of the six complement inhibitors currently approved for PNH, with a focus on the C3/C3b-targeted therapy, pegcetacoplan."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Gastrointestinal Disorder • Hematological Disorders • Pain • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • CD55 • CD59

Three Years On: The Role of Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria (PNH) since Its Initial Approval. (PubMed, Int J Mol Sci) - "This approval was based on results from the Phase 3 PEGASUS study, where pegcetacoplan showed superiority over the C5 inhibitor eculizumab with regard to improving the hemoglobin level in patients with anemia despite eculizumab treatment, and the Phase 3 PRINCE study, where pegcetacoplan showed superiority over supportive care with regard to hemoglobin stabilization and improving the lactate dehydrogenase level in complement inhibitor-naïve patients. In light of this recent indication expansion by the EMA, this article describes how the strong efficacy of pegcetacoplan is linked to its mechanism of action, which provides broad hemolysis control over both intravascular and extravascular hemolysis to improve a range of disease markers and enhance patients' quality of life. Furthermore, additional data and learnings obtained from over 3 years of experience with pegcetacoplan are summarized, including long-term efficacy and safety results, real-world clinical..."

Journal • Review • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Moving toward Individual Treatment Goals with Pegcetacoplan in Patients with PNH and Impaired Bone Marrow Function. (PubMed, Int J Mol Sci) - P3 | "With these new parameters, 40% and 71% of PEGASUS and PRINCE patients had improved haemoglobin; 60% and 71% had an improvement in LDH, and 60% and 43% had an improvement in fatigue scores. Thus, even patients with impaired bone marrow function may achieve clinically meaningful improvements with pegcetacoplan."

Clinical • Journal • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria

The complement model disease paroxysmal nocturnal hemoglobinuria. (PubMed, Eur J Immunol) - "Insights into the complement-mediated pathophysiology ultimately led to regulatory approval of the first-in-class complement inhibitor, eculizumab, in 2007...With five approved complement inhibitors in the clinic and many more being evaluated in clinical trials, PNH remains one of the complement diseases with the highest intensity of clinical research. Mechanistically unexpected breakthrough events occur not only with C5 inhibitors but also with proximal pathway inhibitors, which require further mechanistic elaboration."

Journal • Review • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

Improvements in hematologic markers and decreases in fatigue with pegcetacoplan for patients with paroxysmal nocturnal hemoglobinuria and mild or moderate anemia (hemoglobin ≥10 g/dL) who had received eculizumab or were naive to complement inhibitors. (PubMed, PLoS One) - P1, P3 | "Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan."

Biomarker • Journal • Anemia • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Septic Shock

Severe breakthrough hemolysis during compassionate use of Pegcetacoplan in paroxysmal nocturnal hemoglobinuria: managing an emergency. (PubMed, Blood Transfus) - No abstract available

Journal • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

APL-2 and Pembrolizumab Versus APL-2, Pembrolizumab and Bevacizumab Versus Bevacizumab Alone for the Treatment of Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer and Malignant Effusion (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: Roswell Park Cancer Institute | Trial completion date: Dec 2025 ➔ Apr 2027 | Trial primary completion date: Dec 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Peritoneal Cancer • Sarcoma • Solid Tumor

BREAKTHROUGH HEMOLYSIS IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA TREATED WITH COMPLEMENT INHIBITORS: A MULTICENTER INTERNATIONAL STUDY (EHA 2024) - "5%) as first inhibitor, 68% required a second inhibitor (mainly ravulizumab, 69%), and16% a third inhibitor (mainly danicopan as add on to anti-C5 or Iptacopan single agent, 26%)...5 xULN; 45% of cases weretreated with transfusions (mean of 3 RBCU/patient), 24% increased the dose or frequency of the complementinhibitor (26 anticipated eculizumab, 3 anticipated ravulizumab, 2 increased pegcetacoplan to 3 infusions/weekand 1 added eculizumab for 2 doses), and 2 cases were managed with recombinant erythropoietin; 14% ofpatients were started on anticoagulant prophylaxis and 5 patients, not receiving prophylaxis, experiencedbreakthrough thrombosis (3 pulmonary embolisms and 2 DVT, 4%)... these preliminary data show that BTH complicates PNH course in more than 70% of patients, mainly due toinfections as complement activating triggers. BTH are severe in most cases, requiring transfusions in nearly halfof patients and increase dose/frequency of complement inhibitor in 24%. BTH..."

Clinical • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Embolism • Rare Diseases • Respiratory Diseases • Venous Thromboembolism

INDIRECT TREATMENT COMPARISON OF IPTACOPAN VERSUS PEGCETACOPLAN FOR PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA AND PERSISTENT ANEMIA DESPITE ANTI‑C5 TREATMENT (EHA 2024) - P3 | "In the absence of a head-to-head randomized trial, this analysis matched baseline characteristics of iptacopanand pegcetacoplan trials. When comparing key outcomes across the matched populations, this analysissuggests that iptacopan is more effective than pegcetacoplan at improving Hb levels and provides higher oddsof remaining transfusion free. The results should be interpreted in the context of estimates being derived froman indirect comparison."

Clinical • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

REAL-WORLD CLINICAL OUTCOMES IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA TREATED WITH ECULIZUMAB OR RAVULIZUMAB IN THE US - A RETROSPECTIVE CLAIMS DATABASE ANALYSIS (EHA 2024) - "Current treatments for PNH includecomplement inhibitors such as C5 inhibitors, eculizumab (ECU, FDA-approved in March 2007) and ravulizumab(RAVU, FDA-approved in December 2018), a C3 inhibitor pegcetacoplan (FDA-approved in May 2021), withmost recent option iptacopan, an oral complement factor B inhibitor (FDA-approved in December 2023). Despite treatment with C5 inhibitors, patients with PNH required blood transfusions and experienced PNH-related thrombosis which may potentially indicate a critical unmet need, suggesting that patients might benefitfrom more effective treatment. Figure 1. Time to First PNH-related Thrombosis Event Following Eculizumab and Ravulizumab Initiation"

Claims database • Clinical data • Real-world • Real-world evidence • Retrospective data • Aplastic Anemia • Atypical Hemolytic Uremic Syndrome • Cardiovascular • CNS Disorders • Complement-mediated Rare Disorders • Hematological Disorders • Hypertension • Myasthenia Gravis • Nephrology • Neuromyelitis Optica Spectrum Disorder • Paroxysmal Nocturnal Hemoglobinuria • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Rare Diseases • Respiratory Diseases • Venous Thromboembolism • CFB

Complement inhibition in PHN: from biology to therapy (ISLH 2024) - "The anti-C5 monoclonal antibody eculizumab was the first treatment to improve hemolysis, thrombotic risk, and survival in PNH although at the price of a life-long intravenous fortnightly drug...Ravulizumab, a longer half-life anti-C5 developed from eculizumab, administered every 8 weeks, improved patient convenience, and reduced pharmacokinetic breakthrough hemolysis (BTH) by establishing more stable anti-C5 concentrations. More recently, several other anti-C5 compounds (crovalimab, pozelimab, tesidolumab, cemdisiran, zilucoplan, and coversin) are on study in clinical trials. Upstream inhibition of complement cascade was also explored with the anti-C3 pegcetacoplan, and with the alternative pathway inhibitors iptacopan (anti-factor B) and danicopan (anti-factor D)...Additionally, both anti-C5 and upstream inhibitors do not resolve the unmet need of pharmacodynamic BTH events due to complement amplifying conditions such as infections, traumas, and surgery. In this review,..."

Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

PEGCETACOPLAN C3 INHIBITOR IMPROVE RESIDUAL ANEMIA IN PNH PATIENTS UNDER TREATMENT C5 INHIBITORS. EXPERIENCE TERTIARY HOSPITAL (EHA 2024) - "2/4 were receiving Eculizumab (ECU) 600mg/15 days, 1/4 patient ECU 600 mg/13 days and 1/4 patients 1200 mg/15 days. The effect of improvements in Hb levels and control of underlying hemolysis translates not only to clinicalvariables such as independence of transfusion but also to improvements in patient-reported outcomes. Treating intravascular hemolysis as well as preventing extravascular hemolysis by proximal complementinhibition with PEG may result in better control of disease than treatment with C5i subgroup patients not wellresponse. Figure 1 LDH, Hb and ARC levels pre-PEG, day +14 post-PEG, day +28 post-PEG and last sample."

Clinical • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

SUCCESSFUL TREATMENT WITH ANTI-COMPLEMENT MOLECULE PEGCETACOPLAN IN LIVER TRANSPLANTATION FOR BUDD-CHIARI SYNDROME IN A PATIENT WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA. (EHA 2024) - "He initiated eculizumab treatment in 2009 with a goodresponse until 2014, when he suffered continuous hemolytic crises and poor hemolytic control despiteincreasing the dose up to 1200 mg/week. Pegcetacoplan, is indicated as a second-line treatment for anemic patients after C5inhibitor therapy. While it appears, the primary clinical benefit is in patients with EVH following iC5 treatment,C3 inhibition is shown to be highly effective in controlling both extravascular and IVH. It serves as an excellentalternative for patients with inadequate control of IVH with C5 inhibitors, irrespective of the degree of anemia."

Clinical • Anemia • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hepatology • Paroxysmal Nocturnal Hemoglobinuria • Portal Hypertension • Rare Diseases • Thrombosis • Transplantation

INJECTION SITE REACTIONS IN ADULT PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA WHO RECEIVED SUBCUTANEOUS PEGCETACOPLAN MONOTHERAPY FOR UP TO 3 YEARS (EHA 2024) - P3 | "Most ISRs were mild; none led to treatment discontinuation. Over time, the percentage of patients reportingISRs decreased, possibly because patients gained confidence with self-administration. These results, along withhigh compliance and decreased fatigue (evident from higher FACIT-Fatigue scores), suggest ISRs are likely nota barrier to PEG treatment."

Clinical • Monotherapy • CNS Disorders • Complement-mediated Rare Disorders • Fatigue • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

PEGCETACOPLAN MANAGEMENT IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA UNDERGOING MAJOR SURGERIES (EHA 2024) - "In 2010, he started treatmentwith eculizumab because of renal function deterioration after an acute hemolytic episode. This is the first report of patients with PNH treated with pegcetacoplan undergoing major surgeries in Spain. Inthese patients, the perioperative dose increase was successful in preventing the development of abreakthrough hemolytic crisis."

Clinical • Surgery • Anemia • Anesthesia • Aplastic Anemia • Benign Prostatic Hyperplasia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Musculoskeletal Diseases • Oncology • Orthopedics • Ovarian Cancer • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

IMPROVEMENT IN IRON OVERLOAD WITH PEGCETACOPLAN THERAPY IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PREVIOUSLY TREATED WITH ECULIZUMAB (EHA 2024) - P3 | "IO, as defined in this analysis, resolved with PEG in ≥50% of patients with PNH who had residual anemia andbaseline IO with prior ECU treatment. Persistently high ferritin levels in ECU-experienced patients during 32weeks of PEG may reflect that this period was too short to observe changes in iron stores. The normalization ofTSAT, increased hepcidin, and decreased ARC with PEG suggest that controlled EVH and improved anemia withPEG can improve iron regulation (vs elevated ferritin levels seen with C5i treatment)."

Clinical • Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis

THROMBOSIS AND MENINGOCOCCAL INFECTION RATES IN PEGCETACOPLAN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IN THE POST-MARKETING SETTING (EHA 2024) - "In patients who received the C5 inhibitor (C5i) eculizumab inclinical trials, thrombosis rates decreased from 7...[1] Treatment with the C5i ravulizumab had a similar thrombosisrate of 1... These findings suggest that the thrombosis rate on pegcetacoplan is low overall and comparable to rates onC5is in patients with PNH. A potential confounder is the real-world nature of the data, which may be subject tounderreporting. There have been no reported meningococcal infections, suggesting effective risk mitigationstrategies."

Clinical • P4 data • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Influenza • Meningococcal Infections • Paroxysmal Nocturnal Hemoglobinuria • Pneumococcal Infections • Pneumonia • Rare Diseases • Respiratory Diseases • Thrombosis