Analytical and functional similarity of biosimilar Elizaria® with eculizumab reference product

Gusarova, Valentina; Degterev, Maksim B.; Lyagoskin, Ivan V.; Simonov, V. I.; Smolov, Maxim; Taran, Sergey; Shukurov, R. R.

doi:10.1016/j.jpba.2022.115004

Cited by 11 publications

(5 citation statements)

References 29 publications

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“…Those previously on eculizumab were subsequently switched once it was available. 70 A phase-3 trial confirmed non-inferiority compared to eculizumab with respect to LD control, secondary outcomes, and safety parameters. 48 How these biosimilars, given fortnightly, will fit into health systems that already have ravulizumab remains to be seen, but could at least provide a more affordable option for the many countries still without C5 inhibition for PNH.…”

Section: Treatment Pathwaysmentioning

confidence: 88%

Paroxysmal Nocturnal Hemoglobinuria: Current Management, Unmet Needs, and Recommendations

Oliver,

Patriquin

2023

JBM

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Paroxysmal nocturnal hemoglobinuria (PNH) is an ultra-rare, acquired clonal abnormality, which renders hematopoietic cells exquisitely sensitive to complement-mediated destruction. Classical features of PNH include intravascular hemolytic anemia, increased thrombotic risk, and manifestations related to end-organ damage (eg fatigue, chest pain, dyspnea, renal failure, and pulmonary hypertension). With supportive care alone, mortality rate of patients with PNH is approximately 35%. The anti-C5 monoclonal antibody, eculizumab, was the first targeted therapy approved for PNH, and led to improved hemoglobin, quality of life, reduced transfusion need, reduced thrombosis, and greater overall survival. More recently, therapeutics such as longer acting anti-C5 (ravulizumab) and anti-C3 (pegcetacoplan) medications have been approved, along with other novel therapeutics in late-stage clinical trials. Biosimilars of eculizumab are also now available. Proximal inhibitors (against C3, factor B, and factor D) have shown significant improvements in hemoglobin and transfusion-avoidance in patients who remain anemic despite C5 inhibition. Despite these novel therapies, some unmet challenges remain, including management of breakthrough hemolysis, clinically significant iatrogenic extravascular hemolysis, optimal management in pregnancy, and infection risk mitigation as new targets in the complement system are blocked. In addition, the use of self-administered subcutaneous and oral therapies raises concerns around treatment adherence and the risks of uncontrolled terminal complement. Given the ultra-rare nature of PNH, development is underway of a centralized international registry to capture and analyze the data as they mature for various new therapies and characterize the clinical challenges related to PNH management.

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Section: Treatment Pathwaysmentioning

confidence: 88%

Paroxysmal Nocturnal Hemoglobinuria: Current Management, Unmet Needs, and Recommendations

Oliver,

Patriquin

2023

JBM

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“…We are also closer to the patients as we partner during the development of optimal treatment strategies and trial concepts. Furthermore, with the rise of the first biosimiliars, 106,107,135 prices for complement inhibitors hopefully will eventually become more reasonable with competition 136 as even the long available C5i eculizumab, which has generated impressive revenues 137 is "unaffordable for more than half of the world." 138 This calls for closer international collaboration not only between countries with well-endowed health care systems but between all countries and hopefully all pharmaceutical players.…”

Section: Acknowledgmentsmentioning

confidence: 99%

Paroxysmal nocturnal hemoglobinuria: Where we stand

Panse

2023

American J Hematol

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For the last 20 years, therapy of paroxysmal nocturnal hemoglobinuria (PNH) relied-up until recently-on antibody based terminal complement inhibitionon. PNH pathophysiology-a mutational defect leading to partial or complete absence of complement-regulatory proteins on blood cells-leads to intravascular hemolysis and consequences such as thrombosis and other sequelae. A plethora of new drugs interfering with the proximal and terminal complement cascade are under recent development and the first "proof-of-pinciple" proximal complement inhibitor targeting C3 has been approved in 2021. "PNH: where we stand" will try to give a brief account on where we came from and where we stand focusing on approved therapeutic options. The associated improvements as well as potential consequences of actual and future treatments as well as their impact on the disease will continue to necessitate academic and scientific focus on improving treatment options as well as on side effects and outcomes relevant to individual patient lives and circumstances in order to develop effective, safe, and available treatment for all hemolytic PNH patients globally.Note: Due to space limitation the author mostly cites reviews and overviews, giving readers the chance to easily find continuative summaries of potentially interesting topics. He therefore does apologize

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“…Biosimilars to eculizumab, SB12, 55 and ABP959, 41,56 have completed Phase 3 studies and one compound, elizaria, 57 is now licensed and used exclusively in Russsia. The development of biosimilars will enable wider and cheaper access to complement inhibition and will hopefully substantially drive down the cost of PNH treatment.…”

Section: Will There Be a Better Terminal Complement Inhibitor?mentioning

confidence: 99%

“…34 C3 mediated EVH, which is "iatrogenic" and a "class" effect of C5 inhibition, is likely to be similar between all C5 inhibitors and hence the importance of upstream complement blockade for managing clinically significant EVH. 24 Biosimilars to eculizumab, SB12, 55 and ABP959, 41,56 have completed Phase 3 studies and one compound, elizaria, 57 is now licensed and used exclusively in Russsia. The development of biosimilars will enable wider and cheaper access to complement inhibition and will hopefully substantially drive down the cost of PNH treatment.…”

Section: What Is An Ideal Complement Inhibitor In Pnh?mentioning

confidence: 99%

Paroxysmal nocturnal hemoglobinuria: Where are we going

Kulasekararaj

Λαζανά

2023

American J Hematol

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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare nonmalignant clonal hematological disorder that is characterized by a deficiency of the GPI-linked complement regulators on the membrane of hematopoietic cells, which renders them susceptible to complement-mediated damage. Intravascular hemolysis (IVH), increased tendency for thrombosis, and bone marrow failure constitutes hallmark features of the disease and are associated with high morbidity and mortality. The introduction of C5 inhibitors radically changed disease outcomes, offering a near-normal life expectancy to PNH patients. However, residual IVH and extravascular hemolysis (EVH) continue to occur during C5-inhibitor treatment, leaving a significant proportion of patients' anemic and some remaining transfusion dependent. Quality of life (QoL) has also been an issue with the regular intravenous (IV) administrations of the currently licensed C5 inhibitors. This has led to the exploration and development of novel agents, targeting different parts of the complement cascade, or having different formulations allowing for self-administration. Longer-acting and subcutaneous formulations of C5 inhibitors have shown equal safety and efficacy, whereas the development of proximal complement inhibitors is changing completely the therapeutic landscape of PNH, limiting both IVH and EVH and showing superior efficacy over C5 inhibitors, especially in improving haemoglobin. Combination treatments have also been tested with promising results. This review summarizes the current therapeutic options, gaps in anticomplement therapy and discusses emerging therapeutic approaches for PNH. Untreated (i.e., complement inhibitor naïve) PNH is a disease purely or only manifested by IVH, due to lack of complement regulatory GPI proteins, especially CD55 (DAF-Decay Accelerating Factor) and CD59 (MIRL-Membrane Inhibitor of Reactive Lysis), on erythrocytes and all other progeny derived from stem cells, which has acquired somatic PIG-A mutation. 6 Both, early complement activation (mediated by

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Analytical and functional similarity of biosimilar Elizaria® with eculizumab reference product

Cited by 11 publications

References 29 publications

Paroxysmal Nocturnal Hemoglobinuria: Current Management, Unmet Needs, and Recommendations

Paroxysmal Nocturnal Hemoglobinuria: Current Management, Unmet Needs, and Recommendations

Paroxysmal nocturnal hemoglobinuria: Where we stand

Paroxysmal nocturnal hemoglobinuria: Where are we going

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