Innovative approaches to biologic development on the trail of CT-P13: biosimilars, value-added medicines, and biobetters

Abstract

The biosimilar concept is now well established. Clinical data accumulated pre- and post-approval have supported biosimilar uptake, in turn stimulating competition in the biologics market and increasing patient access to biologics. Following technological advances, other innovative biologics, such as “biobetters” or “value-added medicines,” are now reaching the market. These innovative biologics differ from the reference product by offering additional clinical or non-clinical benefits. We discuss these innovative biologics with reference to CT-P13, initially available as an intravenous (IV) biosimilar of reference infliximab. A subcutaneous (SC) formulation, CT-P13 SC, has now been developed. Relative to CT-P13 IV, CT-P13 SC offers clinical benefits in terms of pharmacokinetics, with comparable efficacy, safety, and immunogenicity, as well as increased convenience for patients and reduced demands on healthcare system resources. As was once the case for biosimilars, nomenclature and regulatory pathways for innovative biologics require clarification to support their uptake and ultimately benefit patients.

Perspectives on Subcutaneous Infliximab for Rheumatic Diseases and Inflammatory Bowel Disease: Before, During, and After the COVID-19 Era

“…Infliximab is an example of how innovation has led to treatment evolution and improvements—from the introduction of the reference product in 1998, followed by the approval of the first infliximab biosimilar (CT-P13) in 2013, and the approval of CT-P13 SC in Europe in 2019 [ 13 ]. Infliximab is the most widely studied and used anti-tumour necrosis factor (TNF) biologic for therapy of chronic immune-mediated diseases [ 23 – 25 ].…”

“…As well as being the first infliximab biosimilar to receive regulatory approval from the European Medicines Agency (EMA) and United States (US) Food and Drug Administration (FDA) [ 13 ], CT-P13 was recognised as the first biosimilar monoclonal antibody in Japan and South Korea [ 30 , 31 ]. Global regulatory acceptance was based on the pivotal PLANETRA and PLANETAS studies in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), respectively [ 32 , 33 ].…”

“…For CT-P13 SC, two pivotal studies demonstrated non-inferiority to CT-P13 IV in terms of efficacy (in part 2 of the phase I/III CT-P13 SC 3.5 study in patients with RA) [ 18 ] and PK (in part 2 of the phase I CT-P13 SC 1.6 study in patients with IBD) [ 19 ]. CT-P13 SC provided a more stable drug exposure than CT-P13 IV in both trials, with levels consistently higher than the target therapeutic concentration, representing a pharmacological advantage for CT-P13 SC [ 11 , 13 , 18 , 19 ]. While the pivotal studies included CT-P13 IV dose loading prior to week 6, given predicted exposure and efficacy were comparable between the CT-P13 SC and CT-P13 IV arms from week 6 onwards.…”

“…Recent technological advances have driven the development of innovation in biologics through other modifications, such as the first subcutaneous (SC) formulation of infliximab, CT-P13 SC. Technological innovation has resulted in a biobetter status for CT-P13 SC (and hence designation as a value-added medicine or a biobetter), as it offers significant clinical benefits including improved pharmacokinetics (PK) and a more convenient mode of delivery compared with intravenous (IV) infliximab [ 13 , 14 ]. Availability of CT-P13 SC may have facilitated treatment changes during the pandemic, allowing a shift in administration route from IV to SC, and correspondingly, from in-clinic to at-home treatment, mitigating the risk of nosocomial or commute-related SARS-CoV-2 exposure [ 15 , 16 ].…”

The Evolution of Biologics Administration From Intravenous to Subcutaneous: Treatments for Inflammatory Bowel Disease Go Home

“…Whether SC formulations should be defined as biobetters will need further investigations, because this area of debate is novel for both regulators and experts. 6 Nevertheless, given the reported data of equivalence an important factor in guiding treatment's choice might be patients' preference as this will ensure optimal compliance to therapy and ultimately improve patient confidence with health outcomes. 7,8 A prospective survey performed among 100 anti-tumor necrosis factor (TNF)naive patients with CD revealed that most patients preferred an anti-TNF administered by SC injection rather than by IV infusion.…”