Biosimilars Offer New Hope for European Patients Facing High Eculizumab Costs

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As the high cost of eculizumab continues to limit patient access, biosimilars offer a promising solution to improve affordability and expand treatment options for complement-mediated diseases like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), as backed by a new review showing growing biosimilar use in Europe.¹

The review, published in BioDrugs, aimed to highlight the value of introducing biosimilars to eculizumab for treating PNH and aHUS—2 rare, life-threatening complement-mediated diseases—focusing on how eculizumab changed outcomes for patients and why biosimilars could help lower costs and improve access.

PNH, a condition that causes the immune system to attack red blood cells, has an estimated prevalence of 1 to 9 per 100,000 people in the US and a prevalence of up to 15.9 per 1 million globally, though exact rates remain uncertain due to its rarity.^2,3 aHUS is a rare kidney disease caused by the lining of blood vessels to become damaged, leading to blood clots and possible kidney failure.⁴ There are fewer than 625 known cases of aHUS in the US, according to the aHUS Foundation, the risk of developing aHUS being higher for those that have a family history of the condition, such as a parent, grandparent, or sibling affected by it.⁵

Overall Biosimilar Experience in Europe

Biosimilar approval in the European Union (EU) and US follows a strict, stepwise regulatory pathway led by the European Medicines Agency (EMA) and FDA.¹ This process relies on comparability studies that assess analytical, nonclinical, and clinical similarities to a reference product. It begins with detailed analytical characterization, followed by nonclinical studies if needed, and clinical trials to confirm biosimilarity and rule out meaningful differences.

However, for rare diseases like those treated with orphan drugs, large phase 3 trials are often impractical due to small, diverse patient populations and recruitment challenges. Regulators increasingly favor robust analytical and pharmacokinetic data over extensive efficacy trials to streamline biosimilar approval and improve patient access.

Extrapolation is a key aspect of the biosimilar approval process, allowing regulatory agencies like the EMA and FDA to approve a biosimilar for all the indications of its reference product, even if clinical trials were conducted in only 1. This is permitted when there is strong scientific justification that the biosimilar shares the same mechanism of action across all approved indications and that the studied population is representative. More than 15 years of clinical and real-world experience with biosimilars, including those of adalimumab such as Amgevita, Hyrimoz, and Imraldi, have shown no new safety or efficacy issues in either tested or extrapolated indications.

Clinical studies and real-world data, such as those in non-infectious uveitis and inflammatory bowel disease, confirm that biosimilars perform comparably to the reference product. These findings validate the totality-of-the-evidence approach and support extrapolation as a scientifically sound and practical strategy, enhancing trust and uptake among health care providers.

The authors noted key differences between switching and substitution in the context of biosimilars. Switching is a physician-led decision to change from a reference product to a biosimilar—or between biosimilars—while substitution occurs at the pharmacy level without prescriber input. Although the EMA provides guidance, regulation of these practices lies with individual European countries. As biosimilar use expands, switching is increasingly common. Evidence from numerous studies, involving more than 20,000 patients, shows no significant issues with efficacy, safety, or immunogenicity, supporting the safe and effective use of switching in clinical practice.⁶

Hope for Eculizumab Biosimilars in Europe

EMA-approved eculizumab biosimilars, such as SB12 (Samsung Bioepis), ABP 959 (Amgen), and Elizaria (Generium), are expected to improve access to treatment by reducing costs through market competition. In addition to the EU, eculizumab biosimilars have also been approved in the US, UK, Republic of Korea, and Russia; however, Elizaria’s approval is limited to Russia’s less stringent regulatory framework.

Biosimilarity was confirmed through extensive analytical and functional testing, demonstrating high similarity in structure, mechanism of action, and critical attributes like C5 inhibition. Clinical studies in patients with PNH confirmed comparable efficacy, safety, and pharmacokinetics between the biosimilars and reference eculizumab. SB12 and ABP 959 underwent rigorous phase I and III trials, while Elizaria’s data, though supportive, may not meet the strict regulatory standards of the EMA or FDA.

Alas, eculizumab remains unaffordable for many, limiting treatment access and leading to high discontinuation rates, partly due to cost. Real-world data from Europe, especially the UK, Norway, and Denmark, demonstrate significant savings and increased usage following biosimilar adoption. However, widespread acceptance requires greater awareness, education, and clinician confidence.

“Over 15 years of experience in biosimilar development and clinical use in Europe have solidified a robust regulatory framework, demonstrating that biosimilars are as safe and efficacious as their reference products…. Increasing awareness of the safety, efficacy, and regulatory maturity of biosimilars is crucial to fostering their uptake and overcoming unmet patient needs,” the authors concluded.

References

1. Jang JH, HanB, Jung J, Russo P, Kulasekararaj AG. The path to accessible care: development and impact of eculizumab biosimilars for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. BioDrugs. 2025;39(2):281-295. doi:10.1007/s40259-025-00707-3

2. Peri C. Paroxysmal nocturnal hemoglobinuria (PNH). WebMD. September 20, 2023. Accessed May 20, 2025. https://www.webmd.com/a-to-z-guides/paroxysmal-nocturnal-hemoglobinuria-pnh

3. Paroxysmal nocturnal hemoglobinuria (PNH). Real Disease Advisor. Accessed May 19, 2025. https://www.rarediseaseadvisor.com/disease-info-pages/paroxysmal-nocturnal-hemoglobinuria-epidemiology

4. Atypical hemolytic uremic syndrome: symptoms and treatment. Cleveland Clinic. Accessed May 20, 2025. https://my.clevelandclinic.org/health/diseases/atypical-hemolytic-uremic-syndrome

5. aHUS (atypical hemolytic uremic syndrome). American Kidney Fund. Updated March 19, 2025. Accessed May 20, 2025. https://www.kidneyfund.org/all-about-kidneys/other-kidney-diseases/ahus-atypical-hemolytic-uremic-syndrome

6. Barbier L, Ebbers HC, Declerck P, Simoens S, Vulto AG, Huys I. The efficacy, safety, and immunogenicity of switching between reference biopharmaceuticals and biosimilars: a systematic review. Clin Pharmacol Ther. 2020;108(4):734-55. doi:10.1002/cpt.1836