Efficacy and safety of proposed natalizumab biosimilar PB006 versus Tysabri® in patients with relapsing remitting multiple sclerosis: Primary data from the Phase III Antelope study
Bernhard Hemmer1, Heinz Wiendl2, Karsten Roth3, Hendrik Wessels3, Josef Höfler4, Cyrill Hornuss5, Bernd Liedert5, Krzysztof Selmaj6
1Department of Neurology, Technical University of Munich, Klinikum rechts der Isar, Munich & Munich Cluster for Systems Neurology (SyNergy), Munich, Germany, 2Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany, 3Polpharma Biologics, Gdansk, Poland, 4Staburo GmbH, Munich, Germany, 5Sandoz Biopharmaceuticals, Holzkirchen, Germany, 6Department of Neurology, University of Warmia & Mazury, Olsztyn, and Center of Neurology, Lodz, Poland
Objective:

The Phase III Antelope study (NCT04115488) was designed to confirm the equivalent efficacy and similarity in safety and immunogenicity of Biosim-NTZ compared to Ref-NTZ in relapsing remitting multiple sclerosis (RRMS) patients.

Background:
Biosimilars are medicines developed to match approved biologics, in terms of analytical comparability, clinical efficacy and safety, aiming to support a sustainable healthcare system by improving access to biologics while reducing healthcare spend. Proposed biosimilar natalizumab (PB006; Biosim-NTZ) was developed to match reference natalizumab (Tysabri®, Biogen; Ref-NTZ), an anti-α4 integrin monoclonal antibody treatment for active RRMS and Crohn’s Disease (US only).
Design/Methods:

This multicenter, double-blind, active-controlled, parallel-group study randomized participants to receive either 300 mg intravenous Biosim-NTZ (n=131), or 300 mg intravenous Ref-NTZ (n=133) every 4 weeks for a total of 48 weeks.

The primary objective was to assess equivalent efficacy, using the difference in cumulative combined unique active (CUA) lesions (new gadolinium-enhanced T1-weighted lesions and new/enlarging T2-weighted lesions) from baseline to Week-24.

For immunogenicity assessment, a subset of patients initially randomized to Ref-NTZ were switched to Biosim-NTZ after 24 weeks of treatment (n=30), for the final 24 weeks. 

Results:

The primary efficacy analysis demonstrated comparable efficacy for cumulative CUA lesions between Biosim-NTZ (n=126) and Ref-NTZ (n=130). The point estimate for difference of cumulative CUA lesions between Biosim-NTZ and Ref-NTZ was 0.17, and the corresponding 95% CI (-0.613 to 0.944) at Week-24 was well within the pre-defined margins (±2.1). The mean of cumulative CUA lesions at Week-24 was 1.4 for Biosim-NTZ [SD: 3.62; range: 0-30] versus 1.9 for Ref-NTZ [3.94; 0-29].

Safety profiles and incidence rate of adverse events were comparable. No cases of progressive multifocal leukoencephalopathy or deaths were reported for either group.

Conclusions:
Analysis of the primary endpoint and safety data suggest that Biosim-NTZ matches Ref-NTZ for efficacy and safety. No new safety signals were observed in the Biosim-NTZ group.