Biosimilar natalizumab (biosim-NTZ) PB006 matched the efficacy, safety, and immunogenicity of reference natalizumab (ref-NTZ) for individuals with relapsing-remitting multiple sclerosis (RRMS), according to the findings of a phase 3 trial published in JAMA Neurology.
Biosimilar medicines are believed to be effective and safe, and also affordable for the treatment of MS. Biosim-NTZ PB006 is the first biosimilar monoclonal antibody developed for treating patients with RRMS. It was developed “in accordance with US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines, which require biosimilars to match the reference medicine in analytical comparability, bioequivalence, safety, efficacy, and immunogenicity, confirming no clinically relevant differences in performance across approved indications,” according to researchers.
For the study, the researchers assessed the similarity between biosim-NTZ and ref-NTZ in efficacy, safety, and immunogenicity in patients with RRMS via the use of statistical equivalence design. The phase 3, parallel-group, randomized, active-controlled trial (Antelope; ClinicalTrials.gov Identifier: NCT04115488) was conducted between October 2019 and March 2021 and took place in 48 centers in 7 different countries (ie, Belarus, Croatia, Georgia, Moldova, Poland, Serbia, and Ukraine). The final patient follow-up visit occurred on August 23, 2021 (24 weeks after the last dosing).
Eligible participants were men and women aged 18-60 years diagnosed with RRMS, as defined by revised McDonald criteria. At screening, the following inclusion criteria applied:
- ≥1 documented relapse within the prior year;
- either ≥1 gadolinium (Gd)-enhancing T1-weighted or ≥9 T2-weighted brain lesions on magnetic resonance imaging (MRI);
- Kurtzke Expanded Disability Status Scale (EDSS) score of 0 to 5.0 (inclusive); and
- John Cunningham virus index of ≤1.5.
Both individuals who were currently receiving disease therapy and those who were not currently receiving disease therapy were included in the study.
The primary study endpoint was the cumulative number of new active lesions on MRI (new Gd-enhancing T1-weighted lesions and new/enlarging T2-weighted lesions without double counting) over 24 weeks. Additional study endpoints included further MRI parameters, annualized relapse rate (ARR), and EDSS score. Tolerability, safety, and immunogenicity evaluations included adverse events, laboratory assessments, and positivity for anti–John Cunningham virus antibodies and antinatalizumab antibodies.
All participants were randomly assigned in a 1:1 ratio to receive intravenous infusions of biosim-NTZ 300 mg or ref-NTZ 300 mg every 4 weeks, from week 0 to week 44 (ie, end-of-study visit: week 48). At week 24, the ref-NTZ group was re-randomly assigned and 30 participants were switched to biosim-NTZ for the remainder of the study.
A total of 264 participants — 131 in the biosim-NTZ arm and 133 in the ref-NTZ arm — were enrolled in the study. The mean participant age was 36.7±9.38 years. Overall, 162 of the patients were women.
The researchers found that at week 24, the model-based mean difference in cumulative number of new active lesions between the biosim-NTZ arm and the ref-NTZ arm was 0.17 (least square means, 0.34±0.34 with biosim-NTZ vs 0.45±0.28 with
ref-NTZ; 95% CI, –0.61 to 0.94 within the prespecified margins of ±02.1). There were no significant differences between the treatment groups across secondary endpoints, safety, tolerability, and immunogenicity evaluations.
The small sample size in the ref-NTZ/biosim-NTZ switch subgroup is a potential limitation of the Antelope trial, even though the equivalence design used in phase 3 biosimilar clinical trials seeks to demonstrate clinical equivalence with the reference medicine.
“This phase 3 trial supports proposed biosim-NTZ as a biosimilar alternative to ref-NTZ for treating RRMS,” the researchers concluded.
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Hemmer B, Wiendl H, Roth K, et al. Efficacy and safety of proposed biosimilar natalizumab (PB006) in patients with relapsing-remitting multiple sclerosis: the Antelope phase 3 randomized clinical trial. JAMA Neurol. Published online January 23, 2023. doi:10.1001/jamaneurol.2022.5007