On 24 September 2024, Alvotech submitted a Citizen Petition to the FDA requesting that the FDA refuse to designate any ustekinumab biosimilar as “interchangeable” with Janssen’s Stelara® that is manufactured using a CHO cell-line system, until the FDA has evaluated the differences in sialyation between the biosimilars and Stelara®.
The FDA will licence a biological product as “interchangeable” with a reference product if it is biosimilar and can be expected to produce the same clinical results as the reference product in any given patient. In addition, there must be no greater risk to the patient in switching from the reference product to the proposed interchangeable version than would be involved in remaining on the reference product.
Alvotech’s Citizen Petition refers to US-approved ustekinumab biosimilars: Samsung Bioepis’ Pyzchiva® (SB17, July 2024), Alvotech/Teva’s Selarsdi™ (April 2024) and Amgen’s Wezlana® (October 2023). The Petition claims that, like Stelara®, Selarsdi® and Wezlana® (both of which the FDA has already licensed as interchangeable ustekinumab biosimilars) are produced using a Sp2/0 host cell line or a glyco-engineered CHO cell-line system, whereas Pyzchiva® and other proposed biosimilars to Stelara® are manufactured using a CHO cell line-system, including Celltrion’s CT-P43/SteQeyma®.
If the FDA was to act on Alvotech’s submission, it would deny “interchangeability” status to Pyzchiva® and SteQeyma®, at least until it had investigated the claimed effects of differences in sialyation.
In its petition, Alvotech argues that the low sialylation of therapeutic proteins associated with CHO-based manufacturing (compared with production of monoclonal antibodies using Sp2) can significantly impact their pharmacokinetics (“PK”), particularly in terms of circulation time, immune clearance, and overall efficacy. Alvotech claims that this means the clinical effects of CHO-derived biosimilars may be different over prolonged periods than Stelara® and those biosimilars manufactured in Sp2/0. The Petition suggests such differences could impact dosing, efficacy, and safety profiles in ways that may not be fully captured by standard interchangeability studies.