Researchers say they were able to create an “antibody lock” that makes infliximab more selective in its activity, making it safer and more effective.
The rheumatoid arthritis (RA) drugs infliximab and adalimumab have revolutionized autoimmune disease treatment because of their ability to block the activity of tumor necrosis factor alpha (TNFα), but they run the risk of patients developing dangerous immune resistance, thus becoming susceptible to infections or becoming nonresponsive to the drugs themselves.
In a new paper published in PLoS Biology, researchers say they were able to create an “antibody lock” (Ab lock) that makes infliximab more selective in its activity, making it safer and more effective. They say they used an immunoglobulin G1 hinge as an Ab lock to cover the TNFα-binding site of infliximab by linking it with matrix metalloproteinase (MMP) -2/9 substrate; the MMP enzyme is abundant at the site of RA, where it contributes to the tissue breakdown that is a major consequence of the disease. That generated pro-infliximab, which was specifically activated in the RA region to enhance the selectivity and safety of treatment.
In this mouse study, a high concentration of MMP removed the lock and released pro-infliximab primarily at the site of disease; in nonarthritic tissues where MMP levels were lower, this lock remained closed. In a bacterial challenge, the mice treated with the pro-infliximab had fewer infections.
In addition, anti-infliximab antibodies bound to the locked form of infliximab with less than 1% of the strength with which they bound to infliximab itself, suggesting it may be less immunogenic and so less likely to lead to a lack of response to infliximab.
The researchers say the discovery, if confirmed in human trials, could revolutionize RA treatment and improve quality of life. They say the pro-infliximab has 5 advantages:
Reference
Lu YC, Chuang CH, Chuang KH, et al. Specific activation of pro-Infliximab enhances selectivity and safety of rheumatoid arthritis therapy [published online June 13, 2019]. PLoS Biol. doi: 10.1371/journal.pbio.3000286.
Patient Perceptions of Switching From the Reference Adalimumab to Amjevita During Its Initial Launch
April 20th 2024In a survey of patients with autoimmune arthritis who had been switched from reference adalimumab (Humira) to biosimilar adalimumab-atto (Amjevita; Amgen), most reported preferring the biosimilar and had no concerns about switching.
Decoding the Patent Puzzle: Navigating the Legal Landscape of Biosimilars
March 17th 2024On this episode of Not So Different, Ha Kung Wong, JD, an intellectual patent attorney and partner at Venable LLP, details the confusing landscape that is the US patent system and how it can be improved to help companies overcome barriers to biosimilar competition.
Biosimilars Rheumatology Roundup for February 2024—Podcast Edition
March 3rd 2024On this episode of Not So Different, The Center for Biosimilars® revisited all the major rheumatology biosimilar news from February 2024, including the FDA approval of the 10th adalimumab biosimilar, the promise for an oral delivery system for ustekinumab, and the impact of adalimumab products on COVID-19 antibodies.
Biosimilars Council: PBM Rebate Schemes Cost Americans, Payers $6 Billion
April 10th 2024A report from the Biosimilars Council evaluating IQVIA data found that rebate schemes orchestrated by pharmacy benefit managers (PBMs) are costing US patients and payers billions of dollars by suppressing biosimilar adoption.