Hemmer B, Wiendl H Efficacy and Safety of Proposed Biosimilar Natalizumab (PB006) in Patients With Relapsing-Remitting Multiple Sclerosis: The Antelope Phase 3 Randomized Clinical Trial. Hemmer B, Wiendl H, Roth K, Wessels H, Höfler J, Hornuss C, Liedert B, Selmaj K.JAMA Neurol. 2023 Jan 23. doi: 10.1001/jamaneurol.2022.5007. Online ahead of print
Generic natalizumab or should I say biosimilar natalizumab (PB006) has been tested in a clinical trial and it is considered to be comparable to reference natalizumab.
“Question Does proposed biosimilar natalizumab (biosim-NTZ) PB006 match reference natalizumab (ref-NTZ) in terms of efficacy, safety, and immunogenicity in patients with relapsing-remitting multiple sclerosis (RRMS)?”
“Findings In this randomized, double-blind phase 3 clinical trial (called Antelope), 264 adult patients with RRMS received treatment with either biosim-NTZ or ref-NTZ. At week 24, the model-based mean difference in the cumulative number of new active lesions was similar between treatment groups”.
“Meaning The study demonstrated that biosim-NTZ matches the efficacy, safety, and immunogenicity of ref-NTZ in patients with RRMS”.
I guess we wait to see the price and wonder what NHS will suggest. One wonders how the switch of natalizumab to extended dosing intervals and subcutaneous route is doing, but to be honest that is marketing and that’s not my thing, but our research interest has been anti-drug antibody responses…..
Wonder if ProfA has generated the reagents to study this but in the paper it says “Regarding immunogenicity, at week 24, 104 patients (79.4%) were confirmed positive for treatment-emergent ADAs in the biosim-NTZ and 90 participants (69.0%) in the biosim-NTZ group were NAb-positive.
Now before I report on the natalizumab reference, if we look at the reference natalizumab summary of summary of medical product characteristics at the FDA it says ” Patients …..were tested for antibodies to
natalizumab every 12 weeks. The assays used were unable to detect low to moderate levels of
antibodies to natalizumab. Approximately 9% of patients receiving natalizumab-reference developed
detectable antibodies at least once during treatment. Approximately 6% of patients had positive
15 antibodies on more than one occasion. Approximately 82% of patients who became persistently
antibody-positive developed detectable antibodies by 12 weeks. Anti-natalizumab antibodies
were neutralizing in vitro”.
So will the Sh1 stick about 80% ADA natalizumab me-too verses 10% ADA natalizumab-reference…it could make you concerned….
However read above and it says “The assays used were unable to detect low to moderate levels of
antibodies to natalizumab”, so the figure may be more than 9% indeed in this current study the occurrence of ADA for reference natalizumab was in 98 patients (74.0%) and 88 (66.2%) for ref-NTZ were neutralizing. Overall, ADA and NAb responses to biosim-NTZ mirrored that of ref-NTZ throughout the 48-week treatment period.
So it makes you wonder what is the significance of this 9% is very different from 74% and so makes me think that ADA testing should be put in the hands of an independent assay testing site…because the level of ADA is in the alemtuzumab and sort of shows that the idea that humanised antibodies do not cause immunogenicity (the body recognised the therapeutic and reacts against it) is rather a load of tosh. So is the low level of ADA reported for ocrelizumab a product of the assay or does it protect itself against the generation of ADA. So with the ADA being so common you sort of need to know is there a threshold level of ADA that stop natalizumab working….
Anyway do not forget about ATTACKMS a natalizumab trial when MS first shows itself.
Disclaimer. These are the views of the author