Pharmacokinetic and pharmacodynamic similarity of biosimilar natalizumab (PB006) to its reference medicine. A randomized controlled trial

PB006 (Polpharma Biologics S.A.; marketed as Tyruko®, Sandoz) is an approved biosimilar to natalizumab (Tysabri®; Biogen [ref-NTZ]). This multicenter, double-blind, randomized, single-dose study was conducted to demonstrate pharmacokinetic/pharmacodynamic (PK/PD) similarity between PB006 and ref-NTZ. Healthy participants (<i>N</i> = 453) were randomized to receive 3 mg/kg infusion of PB006, US-licensed or EU-approved ref-NTZ before an 85-day follow-up. Primary PK endpoint was total natalizumab serum concentration over time; secondary PK endpoints explored concentration changes. Primary PD endpoints compared CD19+ cell counts and percentage α4-integrin receptor saturation, per natalizumab’s mechanism of action. Secondary PD endpoints explored serum changes in sVCAM-1 and sMAdCAM-1, CD34+ and CD19+ cells. Safety, tolerability, and immunogenicity were assessed. The primary PK endpoint was met, with 90% confidence intervals (CIs) of the geometric mean for serum test/reference ratios contained within a prespecified margin (0.8–1.25). All primary PD endpoints were met, with 90% and 95% CIs within this similarity margin for baseline-adjusted CD19+ cell counts and percentage α4-integrin receptor saturation. All secondary endpoints were similarly contained, except sVCAM. No notable differences in safety, tolerability or immunogenicity were observed. Similarity was confirmed, with PB006 demonstrating PK/PD behavior consistent with that of ref-NTZ. EudraCT number 2019 -003,874-15 PB006(developed by Polpharma Biologics SA.; and marketed as Tyruko®by Sandoz) is an approved biosimilar to the reference medicine,natalizumab (Tysabri®,Biogen [ref-NTZ]), used totreat relapsing forms of multiple sclerosis. Approved biosimilarmedicines have been shown to be as safe and effective as theirreference medicines via different types of comparisons to thereference medicine, confirming that physicians and patients canexpect the same clinical outcome. Thisstudy was conducted to confirm that PB006 acts the same way in thebody as ref-NTZ. Healthy participants received one dose of eitherPB006, ref-NTZ from the US or ref-NTZ from Europe. During the study,blood samples were tested to confirm how much of each medicine waspresent in participants’ blood, as well as to assess changes inimmune cells or proteins related to how natalizumab works. The studyalso measured whether any treatment caused unwanted side effects orcaused any changes in the immune system that may stop the medicineworking. Theresults showed that PB006 behaved in the same way as ref-NTZ in theblood. All reported side effects were similar between groups and wereas expected for this medicine, and neither PB006 nor ref-NTZ causedany important or unexpected changes to the immune system. This studyshowed that biosimilar natalizumab, PB006, behaves in the same way asref-NTZ, and the same treatment outcomes can be expected.