Analytical comparison of Soliris® and its biosimilar, PRK-001

2020 ◽  
Vol 36 (1) ◽  
pp. 73-86
Author(s):  
M.A. Zhuchenko ◽  
N.V. Orlova ◽  
D.I. Zybin ◽  
V.V. Nikolaeva ◽  
A.A. Klishin ◽  
...  
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Patent Protection ◽  
Reference Product ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Biological Properties ◽  
Post Translational Modifications ◽  
Number Of Patients ◽  
Uremic Syndrome ◽  
Order Structures ◽  
Protection Period

Soliris® (Eculizumab) was approved by regulatory authorities as the first drag for treatment of orphan disease, paroxysmal nocturnal hemoglobinuria, in 2007. Later its use was extended for treatment of atypical hemolytic-uremic syndrome and myasthenia gravis. The high cost, the unavailability of therapy for a number of patients, as well as the expiration of the patent protection period for Soliris®, these factors became the prerequisite for the development of biosimilar medicinal products. Here, comparative analysis of PRK-001 (LLC «Pharmapark») and reference drag product, Soliris® (Alexion Pharmaceuticals, USA), was carried out. Physicochemical biosimilarity assessment has shown complete comparability of both products in terms of protein sequence as well as higher order structures. Post-translation modifications as well as impurity profile were the same too. Neither biosimilar nor reference product had impurity amount exceeding threshold. Biological properties of the reference product and biosimilar were the same. Since the comparability of the both drags has been proven, it can be assumed that PRK-001 is biosimilar of Soliris®. Eculizumab, Soliris, paroxysmal nocturnal hemoglobinuria, physicochemical comparison, post-translational modifications, biosimilar, drag product

scholarly journals Complement-driven anemia: more than just paroxysmal nocturnal hemoglobinuria

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 371-376 ◽  
Author(s):  
Samuel A. Merrill ◽  
Robert A. Brodsky
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Liver Function Tests ◽  
Endothelial Damage ◽  
Complement Inhibitors ◽  
Uremic Syndrome ◽  
Clinically Significant ◽  
Complement Regulator ◽  
New Generation

Abstract Atypical hemolytic uremic syndrome (aHUS); hemolysis, elevated liver function tests, and low platelets syndrome; and transplant-associated thrombotic microangiopathy are related conditions, in that many patients harbor germline heterozygous mutations in genes that regulate the alternative pathway of complement (APC). Penetrance is variable because development of clinically significant disease appears to require supervention of a process such as inflammation. Complement activation on the endothelial surfaces leads to endothelial damage, platelet consumption, microthrombi, and a mechanical hemolytic anemia with schistocytes. Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal hematopoietic disease caused by expansion of a stem cell that harbors a somatic mutation in PIGA. PIGA mutant blood cells are deficient in the complement regulator proteins CD55 and CD59, making them susceptible to intravascular hemolysis due to a failure to regulate the APC on erythrocytes. Eculizumab is a monoclonal antibody that binds to C5 and inhibits terminal complement by interfering with the cleavage of C5 by the C5 convertases. The drug is approved by the US Food and Drug Administration for the treatment of aHUS and PNH; however, a new generation of complement inhibitors that block C5 and other components of the complement cascade is showing promise in preclinical and clinical trials.

scholarly journals Complement in hemolytic anemia

Blood ◽  
2015 ◽  
Vol 126 (22) ◽  
pp. 2459-2465 ◽  
Author(s):  
Robert A. Brodsky
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Reticuloendothelial System ◽  
Immunoglobulin M ◽  
Regulatory Proteins ◽  
Cold Agglutinin Disease ◽  
Complement Regulatory Proteins ◽  
Uremic Syndrome ◽  
Alternative Pathway Of Complement

Abstract Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

scholarly journals Complement in hemolytic anemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 385-391 ◽  
Author(s):  
Robert A. Brodsky
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Reticuloendothelial System ◽  
Immunoglobulin M ◽  
Regulatory Proteins ◽  
Cold Agglutinin Disease ◽  
Complement Regulatory Proteins ◽  
Uremic Syndrome ◽  
Alternative Pathway Of Complement

Abstract Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

Complement in hemolytic anemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 385-391 ◽  
Author(s):  
Robert A. Brodsky
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Reticuloendothelial System ◽  
Immunoglobulin M ◽  
Regulatory Proteins ◽  
Cold Agglutinin Disease ◽  
Complement Regulatory Proteins ◽  
Uremic Syndrome ◽  
Alternative Pathway Of Complement

Complement is increasingly being recognized as an important driver of human disease, including many hemolytic anemias. Paroxysmal nocturnal hemoglobinuria (PNH) cells are susceptible to hemolysis because of a loss of the complement regulatory proteins CD59 and CD55. Patients with atypical hemolytic uremic syndrome (aHUS) develop a thrombotic microangiopathy (TMA) that in most cases is attributable to mutations that lead to activation of the alternative pathway of complement. For optimal therapy, it is critical, but often difficult, to distinguish aHUS from other TMAs, such as thrombotic thrombocytopenic purpura; however, novel bioassays are being developed. In cold agglutinin disease (CAD), immunoglobulin M autoantibodies fix complement on the surface of red cells, resulting in extravascular hemolysis by the reticuloendothelial system. Drugs that inhibit complement activation are increasingly being used to treat these diseases. This article discusses the pathophysiology, diagnosis, and therapy for PNH, aHUS, and CAD.

scholarly journals Partial ADAMTS13 deficiency in atypical hemolytic uremic syndrome

Blood ◽  
2013 ◽  
Vol 122 (8) ◽  
pp. 1487-1493 ◽  
Author(s):  
Shuju Feng ◽  
Stephen J. Eyler ◽  
Yuzhou Zhang ◽  
Tara Maga ◽  
Carla M. Nester ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Gene Polymorphisms ◽  
Rare Variants ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Number Of Patients ◽  
Complement Dysregulation ◽  
Key Points ◽  
Uremic Syndrome ◽  
Adamts13 Deficiency

Key Points Reduction in ADAMTS13 function and complement dysregulation coexist in a significant number of patients with aHUS. Variations in the ADAMTS13 gene (polymorphisms and rare variants) are partly responsible for the reduced ADAMTS13 function in aHUS.

Sign in / Sign up

Export Citation Format

Share Document