Spotlight On: Presentation of biosimilar Remicade data at next month’s EULAR congress

As progression towards a workable biosimilars pathway in the US continues to hit roadblocks, Europe moves closer to the potential approval of the first biosimilar monoclonal antibody; a version of Remicade developed by the South Korean company Celltrion. See Spotlight On: EMA accepts submission for first biosimilar antibody product Onlookers are expected to keenly devour any new information about the product – which could have implications for other biosimilar antibody developments – when pivotal Phase III results are unveiled at the Annual European Congress of Rheumatology next month.

Data keenly anticipated

Based on comments made by Celltrion’s partner Hospira in its Q1 conference call, the clinical data we can expect to see next month sounds promising. Sanford C. Bernstein analyst Ronny Gal – who has been tracking the development of CT-P13 from the clinical to regulatory setting – expects the data to impress; he told FirstWord "given the nature of biosimilar development, closely aligned via iterative interaction with the regulator, I believe it’s highly unlikely that Celltrion would have submitted to the EMA unless its product was quite close. I expect the data to reflect that and certainly believe CT-P13 has hit primary endpoints regarding ACR20 with similar results to the innovator".

Others are more cautious about the progression of CT-P13 through the regulatory process. Despite how closely Celltrion has worked with the EMA, note analysts at Barclays, the "quality of the data and whether it meets equivalence requirements remains pivotal". To gain approval, the product will be required to demonstrate "clinical efficacy within a relative narrow equivalence margin".[2] A recent Barclays investor research note adds "relative to an anticipated 50% ACR20 response rate for branded Remicade, we estimate that the 95% confidence intervals for biosimilar Remicade (CT-P13) would need to fall between 45.5% and 54.5% to demonstrate equivalence. Patient heterogeneity and subjective pain scores mean that equivalence is not guaranteed."

Extrapolation challenges

A secondary consideration is whether the clinical data submitted to the EMA will be sufficient to gain approval for a label that encompasses the seven indications that Remicade is approved for; given that Celltrion has only undertaken clinical trials for rheumatoid arthritis and ankylosing spondylitis.

Successfully gaining ‘full indication’ labelling – Barclays currently estimates the probability at 80 percent or less – will be partially dependent on results from pre-clinical data from Crohn’s disease models (which could demonstrate CT-P13 is highly comparable to the reference product in membrane-bound TNF alpha conditions). It is arguably a lack of access to this pre-clinical data that will be most frustrating to interested stakeholders in the biosimilars space. Duncan Emerton – biosimilars practice lead at Datamonitor Consulting – told FirstWord “the pre-clinical characterisation data would be very interesting, as it would show just how ‘biosimilar’ CT-P13 is to Remicade that’s manufactured using 21st century processes from an analytical perspective. But we can’t have everything”.

Clearly there are risks attached to potential requirement from the EMA for Celltrion to undertake an additional clinical trial in order to gain a broader label; beyond the cost involved with each trial there is an increased chance that the product will fail to demonstrate a pre-specified equivalence margin, says Barclays. The commercial implications remain open to conjecture, some suggest tendering issues may be impacted by limited labelling for biosimilars and infer off-label prescribing will pick up some of the revenue slack. Others are more sceptical; Kate Keeping – an associate director at Decision Resources – recently told FirstWord that while physicians’ interest in biosimilar MAbs remains high due to the cost benefit "interviews suggest a broad level of discomfort with extrapolation".

Outlook

There is little doubt that disclosure of Phase III data for CT-P13 will fuel momentum for what appears to be a pivotal stage of development for the biosimilars market, particularly within a European context. Challenges remain, nonetheless, including the notion of ‘product drift’[2] where changes in the manufacturing process for the originator brand (which did not require regulatory approval) both move the goal posts for biosimilar developers (potentially requiring the need for additional bridging studies) and providing an opportunity for branded players to ‘evergreen’ their products by seeking new manufacturing process patents. In the US, potential barriers remain even higher, as evidenced by Abbott’s recent filing of a Citizen’s Petition with the FDA (see Spotlight On: Biosimilars facing further delays in the US?)

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