Eculizumab Biosimilar ABP 959 Demonstrates Similarity to Reference in Patients With PNH

The efficacy and pharmacokinetics of ABP 959, an eculizumab biosimilar from Amgen, and its reference product (Soliris) were similar in patients with paroxysmal nocturnal hemoglobinuria (PNH), new study results presented at the 2023 American Society of Hematology (ASH) Annual Meeting & Exposition, being held December 9-12, 2023, in San Diego, California.¹

Soliris is approved to treat PNH, atypical hemolytic uremic syndrome, generalized myasthenia gravis, and neuromyelitis optical spectrum disorder. It is the most widely used drug to treat PNH. The most recently approved treatment is iptacopan, which FDA approved on December 5, 2023.² Iptacopan is the first oral monotherapy to treat PNH. Soliris is administered by intravenous infusion.

PNH is a rare, life-threatening blood disorder with 6 out of 1 million people diagnosed each year.³ When left untreated, PNH can cause hemolytic anemia, chronic kidney disease, or thrombosis.³ Patients with PNH generally have a poor quality of life, and if it is left untreated, up to 35% of people diagnosed with PNH die within 5 years of diagnosis.⁴

Previous research has confirmed the similarities of ABP 959 with the reference product, including pharmacokinetics (PK), pharmacodynamics (PD) and safety similarities in health adults.

The poster presented at ASH reported on the primary efficacy results from the parallel and crossover comparisons in patients with PNH, as well as additional PK analyses, from a multicenter, randomized, double-blind, active-controlled, 2-period crossover study. All patients received both treatments, either ABP 959 first followed by the reference (ABP 959/reference) or the reference first followed by ABP 959 (reference/ABP 959). A total of 42 patients were randomized in a 1:1 fashion with 20 in the ABP 959/reference arm and 22 in the reference/ABP 959 arm.

Both parallel and crossover comparisons showed similarity of efficacy as determined by hemolysis in patients with PNH. PK similarity between the 2 treatments was demonstrated by analyses of serum total and unbound PK concentrations.

“The results of this study, along with previously demonstrated analytical, non-clinical, clinical PK/PD in healthy adults, and efficacy and safety evaluations in PNH patients, further support a demonstration of no clinically meaningful differences between ABP 959 and eculizumab [reference product],” the researchers concluded.

ABP 959 is already approved for use in the European Union and marketed as Bekemv.⁵ A second eculizumab biosimilar, Epysqli from Samsung Bioepis, was approved in May 2023.⁶

In the United States, the reference product is still protected by its patent. A settlement⁷ between Alexion Pharmaceuticals, the maker of Soliris, and Amgen will keep ABP 959 off the market until March 1, 2025, even if the biosimilar receives FDA approval.

References

1. Kulasekararaj A, Lanza F, Avanitakis A, et al. Efficacy of parallel and crossover analysis as well as pharmacokinetic similarity were confirmed between ABP 959 and eculizumab reference product in patients with PNH. Presented at: 2023 American Society of Hematology Annual Meeting & Exposition; December 9-12, 2023; San Diego, CA. Abstract 4092.

2. Bonavitacola J. FDA approves iptacopan, marking first oral monotherapy for adults with PNH. The American Journal of Managed Care^® website. December 6, 2023. https://www.ajmc.com/view/fda-approves-iptacopan-marking-first-oral-monotherapy-for-adults-with-pnh

3. Paroxysmal nocturnal hemoglobinuria. Cleveland Clinic. Reviewed April 25, 2022. Accessed December 6, 2023. https://my.clevelandclinic.org/health/diseases/22871-paroxysmal-nocturnal-hemoglobinuria

4. Schwartz CE, Stark RB, Borowiec K, Nolte S, Myren KJ. Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria. Orphanet J Rare Dis. 2021;16(1):389. doi:10.1186/s13023-021-02016-8

5. Bekemv. European Medicines Agency. Updated July 6, 2023. Accessed December 6, 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/bekemv

6. Jeremias S. Samsung Bioepis’ eclizumab biosimilar approved in Europe. The Center for Biosimilars^® website. May 31, 2023. Accessed December 6, 2023. https://www.centerforbiosimilars.com/view/first-hematology-biosimilar-approved-in-europe

7. Alexion delays Soliris biosimilar until 2025. Generics and Biosimilars Initiative. August 8, 2020. Accessed December 6, 2023. https://www.gabionline.net/policies-legislation/Alexion-delays-Soliris-biosimilar-until-2025