Understanding Interchangeable Biosimilars
Muna Said, PharmD
3 minutes
Understanding Interchangeable Biosimilars
A biosimilar is a biologic drug highly similar to a reference product, with no clinically meaningful differences in safety, purity, and potency. An interchangeable biosimilar can be substituted at the pharmacy for the reference product without the intervention of the prescribing healthcare provider, similar to how generic drugs are substituted for brand-name drugs. Regular and interchangeable biosimilars differ slightly because interchangeable biosimilars undergo an additional approval process, providing extra data that ensures the biosimilar and its reference biologic can be interchanged without any safety, efficacy, or immunogenicity concerns. This however does not imply that interchangeable biosimilars are superior; all biologics and biosimilars must meet strict quality and safety regulations. The additional data allows interchangeable biosimilars to be more easily substituted at the pharmacy, potentially without needing the pharmacist to contact the healthcare provider. Out of 53 total biosimilars, only 12 are currently interchangeable with their reference products. 1
Cyltezo® (adalimumab-adbm), which was the first interchangeable biosimilar for the treatment of inflammatory diseases, evaluated in a phase 3 trial (VOLTAIRE-CD). Patients aged 18 to 80 years with moderate to severe Crohn’s disease were randomized 1:1 to receive adalimumab reference product (adalimumab-RP; n = 75) or adalimumab-adbm (n = 72). The findings revealed no difference in the primary endpoint, which was defined as the proportion of participants with a clinical response per a decrease of at least 70 points in the CDAI score at week 4 (adalimumab-adbm 90% vs. adalimumab-RP 94%; 95% confidence interval -11.7 to 4.2). Notably, this finding met the predefined criteria demonstrating therapeutic equivalence between adalimumab-adbm and adalimumab-RP. 2,3
In May 2024, the Food and Drug Administration (FDA) approved Yesafili™ (aflibercept-jbvf) and Opuviz™ (aflibercept-yszy) as interchangeable biosimilars to Eylea® (aflibercept). The approvals were granted due to thorough reviews demonstrating that both biosimilars are highly similar to aflibercept, with no significant differences. This included extensive analytical tests, biological assays, and clinical studies. Analytical comparisons involved examining multiple batches of aflibercept-jbvf and aflibercept-yszy against aflibercept across various quality attributes, confirming structural and functional similarity. Clinical data further supported that these biosimilars matched aflibercept in efficacy, safety, and immunogenicity. Based on this comprehensive data, the FDA approved aflibercept-jbvf and aflibercept as interchangeable with Eylea.4
While these examples highlight specific data that underscore the interchangeability of biosimilars, in general, interchangeable biosimilars play a critical role in healthcare by providing more affordable access to essential biologic therapies while meeting rigorous standards of safety and efficacy. They broaden treatment options and foster competition among manufacturers, which can ultimately reduce healthcare costs. By ensuring comparable clinical performance and regulatory compliance, interchangeable biosimilars support healthcare providers in making informed treatment decisions, thereby improving patient outcomes and enhancing the overall efficiency of healthcare delivery.1
|
Table 1: FDA-approved Interchangeable Biosimilars
|
|
Proper Name
|
Brand (Manufacturer)
|
Reference Agent Name
|
Initial FDA Approval Date
|
FDA Approved Indications
|
|
Adalimumab-adbm
|
Cyltezo® (Boehringer Ingelheim)
|
Humira® (adalimumab)
|
August 2017
|
Rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, uveitis
|
|
Adalimumab-afzb
|
Abrilada® (Pfizer)
|
Humira® (adalimumab)
|
November 2019
|
Rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, uveitis
|
|
Adalimumab-ryvk
|
Simlandi® (Teva)
|
Humira® (adalimumab)
|
February 2024
|
Rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, plaque psoriasis, hidradenitis suppurativa, uveitis
|
|
Aflibercept-jbvf
|
Yesafili™ (Biocon Biologics)
|
Eylea® (aflibercept)
|
May 2024
|
Neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy
|
|
Aflibercept-yszy
|
Opuviz™ (Biogen, Samsung Bioepis)
|
Eylea® (aflibercept)
|
May 2024
|
Neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy
|
|
Denosumab-bbdz
|
Jubbonti® (Sandoz)
|
Prolia® (denosumab)
|
March 2024
|
Treatment of postmenopausal women with osteoporosis at high risk for fracture, treatment to increase bone mass in men with osteoporosis at high risk for fracture, treatment of glucocorticoid-induced osteoporosis in men and women at high risk for fracture, treatment to increase bone mass in men at high risk for fracture receiving androgen deprivation therapy for nonmetastatic prostate cancer, treatment to increase bone mass in women at high risk for fracture receiving adjuvant aromatase inhibitor therapy for breast cancer
|
|
Denosumab-bbdz
|
Wyost® (Sandoz)
|
Xgeva® (denosumab)
|
March 2024
|
Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy
|
|
Eculizumab-aeeb
|
Bkemv™ (Amgen)
|
Soliris® (eculizumab)
|
May 2024
|
Paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, neuromyelitis optica spectrum disorder
|
|
Insulin glargine-aglr
|
Rezvoglar™ (Eli Lilly)
|
Lantus® (insulin glargine)
|
December 2021
|
Diabetes mellitus type 1 and type 2
|
|
Insulin glargine-yfgn
|
Semglee® (Biocon)
|
Lantus® (insulin glargine)
|
July 2021
|
Diabetes mellitus type 1 and type 2
|
|
Ranibizumab-eqrn
|
Cimerli™ (Coherus BioSciences)
|
Lucentis® (ranibizumab)
|
August 2022
|
Neovascular (wet) age-related macular degeneration, macular edema following retinal vein occlusion, diabetic macular edema, diabetic retinopathy, myopic choroidal neovascularization
|
|
Ustekinumab-auub
|
Wezlana™ (Amgen)
|
Stelara® (ustekinumab)
|
October 2023
|
Moderate to severe plaque psoriasis, active psoriatic arthritis, moderate to severe Crohn's disease, moderate to severe ulcerative colitis
|
1. Alvarez DF, Wolbink G, Cronenberger C, Orazem J, Kay J. Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States?. BioDrugs. 2020;34(6):723-732. doi:10.1007/s40259-020-00446-7
2. Bhat S, Patel M, Duly K, Choi D. Adalimumab-Adbm: The First Interchangeable Biosimilar for the Treatment of Inflammatory Diseases. Ann Pharmacother. 2022;56(12):1356-1364. doi:10.1177/10600280221082196
3. Hanauer S, Liedert B, Balser S, Brockstedt E, Moschetti V, Schreiber S. Safety and efficacy of BI 695501 versus adalimumab reference product in patients with advanced Crohn's disease (VOLTAIRE-CD): a multicentre, randomised, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021;6(10):816-825. doi:10.1016/S2468-1253(21)00252-1
4. S Food and Drug Administraion (FDA). FDA approves first interchangeable biosimilars to Eylea to treat macular degeneration and other eye conditions. Updated. May 20, 2024. Accessed June 20, 2024.
5. Cyltezo® (adalimumab-adbm). Prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc. 2024.
6. Abrilada® (adalimumab-afzb). Prescribing information. Pfizer Laboratories Div Pfizer Inc; 2024.
7. Simlandi® (adalimumab-ryvk). Prescribing information. Teva Pharmaceuticals USA, Inc. 2024.
8. Yesafili™ (aflibercept-jbvf). Prescribing information. Biocon Biologics. 2024.
9. Opuviz™ (aflibercept-yszy). Prescribing information. 2024.
10. Jubbonti® (denosumab-bbdz). Prescribing information. Sandoz. 2024.
11. Wyost® (denosumab-bbdz). Prescribing information. Sandoz. 2024.
12. Bkemv™ (Eculizumab-aeeb). Prescribing information. Amgen. 2024.
13. Rezvoglar™ (Insulin glargine-aglr). Prescribing information. Eli Lilly and Company; 2024.
14. Semglee® (Insulin glargine-yfgn). Prescribing information. Biocon Biologics Inc.; 2023.
15. Cimerli™ (Ranibizumab-eqrn). Prescribing information. Coherus BioSciences Inc. 2024.
16. Wezlana™ (ustekinumab-auub). Prescribing information. Amgen. 2023.
Share