An agent biologically analogous to the humanized monoclonal antibody natalizumab is as effective and safe as the original reference drug in relapsing-remitting multiple sclerosis (RRMS) and has similar levels of immunogenicity. New research shows that there are
The researchers note that the results of these Phase 3 trials are in the final stages of the regulatory approval process.
“There are biosimilars that are identical to the original drug in terms of all parameters such as efficacy, side effects and immunogenicity, and will likely be an option for reducing the cost of treatment for multiple sclerosis,” he said. Researcher Bernhard Hemmer, M.D., Ph.D., Professor of Neurology, Technical University of Munich, Germany, said: Medscape medical news.
The survey results were published online on January 23rd. Department of Neurology, JAMA.
potential cost savings
Disease-modifying therapies (DMTs), especially targeted biologics, have revolutionized the treatment of MS, including RRMS. Natalizumab, the first targeted biologic therapy approved for RRMS, is highly effective and widely used, Hemmer said.
However, this and other DMTs come at a cost. Biosimilars, drugs that are clinically similar to reference biologics already on the market, can address this issue. In rheumatology and oncology, biosimilars have already demonstrated significant cost savings and improved access to treatment.
Biosimilar natalizumab (biosim-NTZ), developed by Polpharma Biologics, is the first biosimilar monoclonal antibody therapy developed for MS.
Health authorities, such as the U.S. Food and Drug Administration, are calling for controlled Phase 3 trials to confirm that there are no clinically relevant differences between the proposed biosimilar and its reference drug.
A new, multicenter, phase 3, double-blind, randomized trial, known as Antelope, included 264 adult patients with RRMS at 48 centers in 7 Eastern European countries. Most study participants were female (61.4%), with a mean age of 36.7 years for her.
All were randomly assigned to receive intravenous infusions of 300 mg biosim-NTZ or reference natalizumab (ref-NTZ) every 4 weeks for a total of 12 infusions.
At week 24, 30 patients were switched from ref-NTZ to biosim-NTZ for the remainder of their infusions. Regulators are mandating inclusion of such populations to ensure that patients switching from a drug they are taking to a new biosimilar does not raise concerns, Hemmer said. .
Comparable Efficacy and Safety Profiles
The primary efficacy endpoint was the cumulative number of new active brain lesions on MRI.
At baseline, 48.1% of the biosimilar group and 45.9% of the reference group had at least one gadolinium-enhancing lesion. Additionally, 96.9% of the biosimilar group had 15 or more T2 lesions compared to 96.2% of the reference group.
At 24 weeks, the mean difference between biosim-NTZ and ref-NTZ in the cumulative number of new active lesions was 0.17 (least squares means, 0.34 vs. 0.45) with 95% CIs of –0.61 to 0.94, with point estimates of is a prespecified margin of ± 2.1.
Annual recurrence rates (ARR) for biosim-NTZ and ref-NTZ were similar at 24 weeks (0.21 vs 0.15) and 48 weeks (0.17 vs 0.13). Diastolic Disability Status Scale scores were similar between treatment groups at baseline (mean 3.4 vs. 3.2), but were minimally changed at 24 and 48 weeks and were similar in both groups.
The safety profile of RRMS patients receiving natalizumab was as expected. Adverse events of particular interest were few and similar across treatment groups.
The overall adverse event profile of patients switching from ref-NTZ to biosim-NTZ was similar to patients continuing ref-NTZ treatment, indicating no new or increased risks associated with switching. I did.
The incidence of treatment-related adverse events (TEAEs) was similar, 64.9% for biosim-NTZ, 68.9% for ref-NTZ and 73.3% for the switch group. The most reported TEAEs among all treatment groups were nervous system disorders and infections and prevalence.
Progressive multiple leukoencephalopathy (PML) is a rare and potentially fatal demyelinating disease of the central nervous system and is associated with some DMTs (particularly ref-NTZ). Researchers point to infection with the John Cunningham virus (JCV), also known as human polyomavirus, as the cause.
No participant had a JCV positivity index greater than 1.5 at baseline, according to the study protocol. The proportion of anti-JCV antibody-positive patients was similarly distributed between treatment groups throughout the study.
similar immunogenicity
There was strong concordance for treatment-emergent positivity for anti-drug antibodies between the biosim-NTZ and ref-NTZ groups (79.4% vs. 74.0%). This was also the case for anti-natalizumab neutralizing antibodies (69.0% and 66.2%).
“There was nothing to show that they were different in immunogenicity,” Hemmer said.
He added that this could change “as we look at longer time periods,” but that antibodies to natalizumab usually develop “at a very early stage.”
Hemmer noted that there was nothing surprising about this comparison between the proposed biosimilar and the reference drug.
“With the same immunogenicity, the same mechanism of action, and the same dosage, you would expect similar clinical efficacy and a similar side effect profile, and indeed it does,” he said.
Hemmer added that he has no insight into when the drug will be approved, but the developer expects it to be approved later this year.
welcome results
Comments on Medscape Medical NewsTorge Rempe, MD, assistant professor of neurology at the University of Florida School of Medicine and William T. And Janice M. Neely professor of research in MS, said these new results show that the biosimilar matched the reference drug. said welcome. .
“The authors report no significant differences in the primary endpoints of cumulative number of active lesions and the secondary clinical endpoints of annualized recurrence rate and change from baseline Diastolic Disability Status Scale score,” said Dr. Rempe, who was not involved in the study, said.
The study also showed that reported adverse events were similar between the biosimilar and the reference natalizumab, he noted.
However, no cases of progressive multifocal leukoencephalopathy were found during the study period, but more research is needed to determine long-term safety in this area, Rempe said.
Finally, he agreed that the development of such a biosimilar would address the high annual cost of DMT, an area of concern in the multiple sclerosis field.
This study was funded by Polpharma Biologics. Hemmer reports that while conducting research he received individual fees from Polpharma and Sandoz, and outside of submitted research he received individual fees from Novartis, Biocom, and he received TG Therapeutics. He also holds a patent on the genetic determinants of antibodies against interferon-beta and his KIR4.1 antibody in MS. He joins the Novartis Scientific Advisory Board. He has served on the data monitoring and safety committees of AllergyCare, Polpharma Biologics, Sandoz, and TG Therapeutics. He also received a speaker honorarium from Desitin, a grant from He Regeneron for MS research, the Multiple MS EU consortium, the CLINSPECT-M consortium, and funding from the German Research Foundation. Rempe has not reported any related financial relationships.
JAMA Neurology. Published online on January 23, 2023.
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