Coversin SC (nomacopan SC) / Akari Therap - LARVOL DELTA

rVA576 in Adult Mild to Moderate Bullous Pemphigoid Subjects (clinicaltrials.gov) - P2 | N=9 | Completed | Sponsor: AKARI Therapeutics | Phase classification: P2a ➔ P2

Phase classification • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

TWO CASES OF ISOLATED RENAL THROMBOTIC MICROANGIOPATHIES (TMA) POST HAEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) (EBMT 2025) - "Conditioning was with Fludarabine, Cyclosporine and Alemtuzumab...There was no response to nomacopan, defibrotide or eculizumab, despite CH50 inhibition.Renal function improved with time, creatinine now 120 (36-672)... We describe isolated renal TMA. This was unexpected as usual risk factors were absent. Both became hypertensive first followed by deranged renal function."

Clinical • Anemia • Aplastic Anemia • Bone Marrow Transplantation • Cardiovascular • Genetic Disorders • Graft versus Host Disease • Hematological Disorders • Hypertension • Immunology • Thrombocytopenia • Transplantation

CONSENTII: Coversin in PNH in Patients With Resistance to Eculizumab Due to Complement C5 Polymorphisms (clinicaltrials.gov) - P2 | N=1 | Completed | Sponsor: AKARI Therapeutics | Enrolling by invitation ➔ Completed

Trial completion • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy (clinicaltrials.gov) - P3 | N=10 | Terminated | Sponsor: AKARI Therapeutics | N=50 ➔ 10 | Trial completion date: Dec 2025 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ May 2024; The early termination of this study is a business decision following a portfolio reprioritization plan. The decision is not related to any Efficacy, Safety or Clinical concerns regarding Nomacopan/rVA576

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Bone Marrow Transplantation • Hematological Disorders • Pediatrics • Transplantation

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

Complement inhibition in paroxysmal nocturnal hemoglobinuria: From biology to therapy. (PubMed, Int J Lab Hematol) - "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,..."

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

Nomacopan (rVA576) in Transplant Associated Thrombotic Microangiopathy (clinicaltrials.gov) - P3 | N=50 | Recruiting | Sponsor: AKARI Therapeutics | Trial completion date: Jun 2024 ➔ Dec 2025 | Trial primary completion date: Nov 2023 ➔ Jun 2025

Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Hematological Disorders • Pediatrics • Transplantation

Advancements in Bullous Pemphigoid Treatment: A Comprehensive Pipeline Update. (PubMed, Am J Clin Dermatol) - "Rituximab, a CD20 monoclonal antibody, depletes B-lymphocytes and has shown efficacy in severe cases. Dupilumab, targeting interleukin (IL)-4 receptor α and thus blocking IL-4 and IL-13, downregulates type 2 helper (Th2) responses and has demonstrated promising results. Targeting eosinophil-related molecules using bertilimumab and AKST4290 has yielded positive results in clinical trials. Omalizumab, an immunoglobulin (Ig) E antibody, can reduce disease severity and allows corticosteroid tapering in a number of cases. Complement inhibitors such as nomacopan and avdoralimab are being investigated. IL-17 and IL-23 inhibitors such as secukinumab and tildrakizumab have shown potential in a limited number of case reports. Neonatal Fc receptor antagonists such as efgartigimod are under investigation. Additionally, topical therapies and Janus kinase inhibitors are being explored as potential treatments for BP. These novel therapies offer promising alternatives for managing..."

Clinical • Journal • Pipeline update • Review • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • Pruritus • IL13 • IL17A • IL23A • IL4

Transplant Associated Thrombotic Microangiopathy: Acomprehensive Review and Local Experience (ASH 2023) - "eculizumab, a humanized antibody against complement protein, can be highly effective in patients with TA-TMA...Other available treatment options include rituximab and defibrotide. Other therapeutic agents are under clinical trials such as ravulizumab (C5 inhibitor), nomacopan (C5 and leukotriene B4 inhibitor) and narsoplimab (mannan-binding lectin-associated serine protease-2 [MASP-2] inhibitor)...Thus far, the choice is to individualize therapy according to comorbidities, severity of clinical presentation and availability of the treatment options. ConclusionTA-TMA remains a significant clinical challenge for transplant physicians, and more research is needed to improve our understanding of its pathogenesis, diagnosis, and management, particularly in guiding the choice of therapy."

Review • Anemia • Bone Marrow Transplantation • Cardiovascular • Graft versus Host Disease • Hematological Disorders • Hypertension • Immunology • Infectious Disease • Oncology • Thrombocytopenia • Transplantation

Clinical severity classes in COVID-19 pneumonia have distinct immunological profiles, facilitating risk stratification by machine learning. (PubMed, Front Immunol) - P=N/A | "The XGB model indicated sC5b-9, IL-8, MCP1, and prothrombin F1 and F2 were key discriminators in nomacopan-treated patients (CORONET study). Distinct immunological fingerprints from serum biomarkers exist within different severity classes of COVID-19, and harnessing them using machine learning enabled the development of clinically useful triage and prognostic tools. Complement-mediated lung injury plays a key role in COVID-19 pneumonia, and preliminary results hint at the usefulness of a C5 inhibitor in COVID-19 recovery."

Journal • Machine learning • Retrospective data • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases • CXCL8

Akari Therapeutics Reports First Half 2023 Financial Results and Highlights (GlobeNewswire) - "Akari remains on track to start enrollment by the end of 2023 in the registrational Phase 3 study of nomacopan in pediatric HSCT-TMA, which is expected to generate safety and efficacy data that may support U.S. and European regulatory filings for potential marketing authorization in these regions....Adult study design will be an important topic of discussion during a Type C meeting with the U.S. Food and Drug Administration (FDA) scheduled for November 15, 2023....Akari is also moving forward into a registrational Phase 3 double-blind placebo-controlled clinical trial of nomacopan in adult HSCT-TMA with enrollment expected to begin in 2024."

Enrollment status • FDA event • Rare Diseases

Autoimmune blistering diseases: Promising agents in clinical trials. (PubMed, Expert Opin Investig Drugs) - "However, except for rituximab for pemphigus vulgaris, no new drugs have been approved for the treatment of AIBDs in the last decades...Promising results were shown for a variety of new agents including nomacopan, efgartigimod, omalizumab, dupilumab, as well as chimeric autoantibody receptor T cells. Clinical translation in the field of AIBDs is highly active and we anticipate significant advances in the treatment landscape."

Journal • Review • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • Infectious Disease • Pemphigus Vulgaris

"Investigational drugs for TA-TMA: - narsoplimab - pegcetacoplan - ravulizumab - nomacopan" (@sghmd)

CLINICAL RESPONSE TO NOMACOPAN IN THE PAEDIATRIC HSCT-TMA SETTING (EBMT 2023) - P3 | " Patient X, a 6-year-old male underwent a 6/8 HLA-mismatched unrelated cord blood (CB) HSCT conditioned with fludarabine, treosulfan and thiotepa, for relapsed refractory AML in January 2021 post CB HSCT in April 2020... The pathophysiology of HSCT-TMA is complex and multifactorial. It is important to be vigilant for clinical signs and symptoms of TMA and screen appropriately when suspicion arises so patients can receive prompt management and complement inhibition considered early. These data show that nomacopan had a favourable safety profile and controlled complement activity in this patient with severe HSCT-TMA."

Clinical • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Leukemia • Oncology • Pain • Pediatrics • Thrombocytopenia • Transplantation

"$AKTX Poland and U.K. Regulatory Authorities – URPL and MHRA – Approve Use of New, Higher-Yielding Manufacturing Process for Nomacopan in Pivotal Clinical Study https://t.co/VT5BK7GPlo" (@stock_titan)

Clinical

Clinical Response to Nomacopan in the Paediatric HSCT-TMA Setting (TCT-ASTCT-CIBMTR 2023) - "Patient X, a 6-year-old male underwent a 6/8 HLA-mismatched unrelated cord blood (CB) HSCT conditioned with fludarabine, treosulfan and thiotepa, for relapsed refractory AML in January 2021 post CB HSCT in April 2020...Patient X suffered no adverse events related to nomacopan during the 72-day treatment. Conclusion These data show that nomacopan can have a favourable safety profile and can control complement activity in a patient with severe HSCT-TMA."

Clinical • Late-breaking abstract • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Cardiovascular • CNS Disorders • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hypertension • Immunology • Leukemia • Oncology • Pain • Pediatrics • Thrombocytopenia

Immunopathology of Terminal Complement Activation and Complement C5 Blockade Creating a Pro-survival and Organ-protective Phenotype in Trauma. (PubMed, Br J Pharmacol) - "Previous findings of our and other groups revealed that early TCA represents a rational therapeutic target for trauma patients. Nomacopan as a pro-survival and organ-protective drug, could emerge as a promising adjunct to DCR that may significantly reduce the morbidity and mortality in severe TH patients while awaiting transport to critical care facilities."

Journal • Critical care • Hematological Disorders • Immunology • Inflammation • Systemic Inflammatory Response Syndrome

Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (ARREST-BP) (clinicaltrials.gov) - P3 | N=0 | Withdrawn | Sponsor: AKARI Therapeutics | N=148 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy. (PubMed, Pharmaceuticals (Basel)) - "Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101)."

Journal • Review • Bone Marrow Transplantation • Cardiovascular • Hematological Disorders • Hypertension • Infectious Disease • Pediatrics • Thrombosis • Transplantation

Paroxysmal nocturnal hemoglobinuria: advances in the understanding of pathophysiology, diagnosis, and treatment. (PubMed, Pol Arch Intern Med) - "Determinants of modern treatment, such as strategies (complement C5 inhibitors vs hematopoietic stem cell [HSC] allotransplantation), the safety and efficacy of treatment with eculizumab or ravulizumab, policy of initiation and monitoring of treatment, the criteria for response to treatment and final outcomes of treatment are described. Among the new therapeutic agents, crovalimab and C5 inhibitors at a less advanced stage of research are discussed: tesidolumab, pozelimab, zilucoplan, nomacopan, and cemdisiran. The first approved proximal complement pathway inhibitors that primarily prevent extravascular hemolysis, pegcetacoplan, danikopan, and iptacopan, are presented and their potential benefits are highlighted."

Journal • Aplastic Anemia • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Immunology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombosis • Transplantation

Compassionate Use of an Anti-C5 Inhibitor, Nomacopan, Positively Influenced the Course and Progression of Disease in Covid-19 (ATS 2022) - "Interestingly, C5-levels (target of nomacopan) was increased, validating the rationale for anti-C5 treatment of COVID-19 patients. Nomacopan treatment was associated with no noticeable adverse event and without highly elevated as associated with normal C5 and C5a levels."

Late-breaking abstract • Bone Marrow Transplantation • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

"WACKER’s ESETEC® Technology Achieves a 12-Fold Higher Yield in the Manufacture of Akari’s Investigational Nomacopan https://t.co/x8JZZssB0B" (@CisionNews)

Nomacopan Therapy in Adult Patients With Bullous Pemphigoid Receiving Adjunct Oral Corticosteroid Therapy (ARREST-BP) (clinicaltrials.gov) - P3 | N=148 | Recruiting | Sponsor: AKARI Therapeutics | Not yet recruiting ➔ Recruiting | Initiation date: Sep 2021 ➔ May 2022

Enrollment open • Trial initiation date • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology

Evaluation of Nomacopan for Treatment of Bullous Pemphigoid: A Phase 2a Nonrandomized Controlled Trial. (PubMed, JAMA Dermatol) - P2a | "A larger, placebo-controlled randomized clinical trial is warranted to confirm this safety profile and to establish nomacopan as a new therapeutic option for bullous pemphigoid. ClinicalTrials.gov Identifier: NCT04035733."

Clinical • Journal • P2a data • Bullous Pemphigoid • Dermatology • Dermatopathology • Immunology • Pruritus

"$AKTX FDA Agrees to Use of New Higher-Yielding Manufacturing Process for Nomacopan in Pivotal Clinical Studies https://t.co/BWdgi3hcQE" (@stock_titan)

Clinical