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 (P6-4.003)

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.

Disclosure: Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Actelion. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristows. Dr. Wiendl has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Sanofi-Aventis. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Argenx. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for IGES. Dr. Wiendl has received personal compensation in the range of $0-$499 for serving as a Consultant for Immunovant. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Johnson&Johnson. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for UCB. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for PSI CRO Deutschland GmbH. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genzyme. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck Serono. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Wiendl has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi-Aventis. Dr. Wiendl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB. The institution of Dr. Wiendl has received research support from Biogen. The institution of Dr. Wiendl has received research support from Merck. The institution of Dr. Wiendl has received research support from Novartis. The institution of Dr. Wiendl has received research support from Hoffmann LaRoche. The institution of Dr. Wiendl has received research support from Deutsche Forschungsgemeinschaft. The institution of Dr. Wiendl has received research support from Federal Government of Germany. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Wiendl has received publishing royalties from a publication relating to health care. Dr. Roth has received personal compensation for serving as an employee of Polpharma Biologics. Dr. Wessels has received personal compensation for serving as an employee of Polpharma Biologics. Dr. Hoefler has received personal compensation for serving as an employee of Staburo GmbH. Dr. Hornuss has received personal compensation for serving as an employee of Sandoz. Dr. Liedert has received personal compensation for serving as an employee of Sandoz Biopharmaceuticals. Dr. Liedert has received personal compensation for serving as an employee of Boehringer Ingelheim.