Biosimilar SB12 Matches Eculizumab in PNH Treatment Across Diverse Patient Groups

Biosimilar SB12 demonstrated comparable efficacy and safety for paroxysmal nocturnal hemoglobinuria (PNH) to its reference drug, showing similar outcomes across diverse patient groups. | Image Credit: Innovative Creation - stock.adobe.com

Biosimilar SB12 or Epysqli (eculizumab-aagh; Samsung Bioepis) is equivalent to reference eculizumab (Soliris) for treating complement inhibitor-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH), showing no significant differences in transfusion avoidance or hemoglobin stabilization across both Asian and non-Asian subgroups, according to a study published in ejHaem.¹

PNH is a rare blood disorder that causes brown/dark-colored urine during late nights or early mornings, typically affecting men and women between 30 and 40 years old.² PNH can lead to hemolytic anemia, chronic kidney disease, or thrombosis, and individuals with bone marrow disorders are at risk of developing PNH.

PNH arises from a somatic mutation in the phosphatidylinositol glycan class-A gene.¹ This genetic defect leads to a deficiency of crucial glycosylphosphatidylinositol-anchored proteins, specifically CD55 and CD59, on the surface of blood cells. The absence of these regulatory proteins results in uncontrolled activation of the complement system, which then attacks and destroys red blood cells, leading to intravascular hemolysis. Episodes of severe hemolysis, known as paroxysms, are often triggered by stressors such as surgery, infection, or inflammation.

The FDA approved SB12 in July 2024 for both PNH and atypical hemolytic uremic syndrome, based on results from phase 1 (NCT03722329) and phase 3 studies (NCT04058158).³ This approval was the second eculizumab biosimilar approved, following Bkemv (eculizumab-aeeb) in May 2024.

Researchers conducted a randomized, double-blind phase 3 study between August 2019 and October 2021 at 24 centers across 8 countries to evaluate treatment sequences for PNH.¹ There were 50 adult patients with PNH who were randomized to treatment sequence 1 (TS1, SB12-ECU; n = 25) or 2 (TS2, ECU-SB12; n = 25). Both treatments were administered intravenously, starting with 600 mg weekly for the first 4 weeks, increasing to 900 mg in the fifth week, and then 900 mg biweekly thereafter. At week 26, patients were switched to the alternative treatment, continuing until week 50.

The phase 3 study had Asian patients constituting 54% of the total enrollment. Of the 25 patients randomized to TS1 (SB12-ECU), 60% were Asian and 40% were non-Asian. For the 25 patients randomized to TS2 (ECU-SB12), the distribution was 48% Asian and 52% non-Asian.

The 95% CIs for the mean difference in lactate dehydrogenase (LDH) levels at week 26 between SB12 and eculizumab fell within the predefined equivalence margins for both Asian patients (SB12-ECU, –12.02; 95% CI, −126.87 to 102.83) and non-Asian patients (SB12-ECU, 76.12; 95% CI, −56.75 to 208.99), indicating that SB12 is equivalent to eculizumab in terms of LDH levels for both groups.

The 90% CI for the ratio of time-adjusted area under the effect curve of LDH between SB12 and eculizumab indicated equivalence in Asian patients (SB12/ECU, 1.01; 90% CI, 0.92-1.10), as it fell within the predefined equivalence margin. This comparable outcome was also observed in non-Asian patients, where the ratio was 1.15 with a 90% CI of 0.90 to 1.46.

LDH levels showed a significant drop in both Asian and non-Asian participants after the initial dose, remaining below 2 times the upper limit of normal from week 3 onward. Prior to screening, the mean packed red blood cell (pRBC) units transfused over 12 months were 6.4 units in planned TS1 (SB12-ECU) and 3.8 units in planned TS2 (ECU to SB12).

Throughout the study, the mean number of pRBC units transfused was similar between treatment sequences for Asians (planned TS1, 4.6 units; planned TS2, 4.5 units) and non-Asians (planned TS1, 0.5 units; planned TS2, 1.0 units).

Across the entire study population, 60% of patients received at least one unit of pRBCs in the year before screening, with slightly more in TS1 (64%) than TS2 (54%). Transfusion avoidance was observed in 68.1% of patients receiving SB12 and 72.9% of patients receiving eculizumab, with a difference of -5.3% (95% CI, –18.9% to 8.4%; P = .4492).

In the Asian subgroup, there was a noticeable increase in transfusions in TS2 over time (from 41.7% to 60%) compared with TS1 (from 57.1% to 76.9%). Conversely, non-Asian subgroups showed similar rates of transfusion avoidance between TS1 (70% to 100%) and TS2 (76.9% to 84.6%).

When analyzing hemoglobin stabilization in Period 1 subjects (treated with SB12 or eculizumab before switching), 2 criteria were used due to a lack of standardization in measurement. Using the less stringent Criterion 1, the difference in hemoglobin stabilization between SB12 and eculizumab (SB12-ECU) was 6.3% (95% CI, –21.5% to 34.1%) across the entire study population. This difference was more pronounced in Asian subjects, at 25% (95% CI, –10.9% to 60.9%), and non-Asian subjects showed a difference of –6.9% (95% CI, –43.4% to 29.6%).

Under the more stringent Criterion 2, the overall difference in hemoglobin stabilization (SB12-ECU) was 2.5% (95% CI, –24.8% to 29.8%). For Asian subjects, this difference was 15.5% (95% CI, –22.6% to 53.6%), and for non-Asian subjects, it remained –6.9% (95% CI, –43.4% to 29.6%).

In a study analyzing patients who received at least one dose of either SB12 or eculizumab, 53% were Asian and 47% were non-Asian. Treatment-emergent adverse events (TEAEs) were observed in 84.6% of Asians and 87% of non-Asians, with both subgroups experiencing similar incidence and safety profiles between SB12 and eculizumab, and most TEAEs being mild, moderate, and transient.

Despite these comparable safety profiles, the current modest price difference between SB12 and reference eculizumab limits its potential to significantly improve treatment accessibility in low-income countries, highlighting the need for further cost reduction in manufacturing and distribution to enhance access to this vital therapy.

“The safety profiles were also comparable between SB12 and ECU-treated patients by race subgroup (Asians and non-Asians), supporting the clinical use of SB12 for the treatment of PNH patients globally,” study authors concluded.

References

1. Jang JH, Tomuleasa C, Oliynyk H, et al. Epysqli (SB12; biosimilar to reference eculizumab) in Asian and non-Asian patients with paroxysmal nocturnal hemoglobinuria: subgroup analysis of a global phase III randomized controlled trial. EJHaem. 2025;6(2):e70020. Published 2025 Mar 21. doi:10.1002/jha2.70020
2. Paroxysmal nocturnal hemoglobinuria (PNH): symptoms & treatment. Cleveland Clinic. April 25, 2022. Accessed July 1, 2025. https://my.clevelandclinic.org/health/diseases/22871-paroxysmal-nocturnal-hemoglobinuria
3. Jeremias S. FDA approves Epysqli as second Soliris biosimilar. The Center for Biosimilars^®. July 22, 2024. Accessed July 1, 2025. https://www.centerforbiosimilars.com/view/fda-approves-epysqli-as-second-soliris-biosimilar