FKB327 ( Hulio ) is a proposed biosimilar of the Adalimumab Reference Product ( RP; Humira ).
A randomized, double-blind, phase 3 study compared the efficacy, safety, pharmacokinetics and immunogenicity of FKB327 and Adalimumab RP in patients with active rheumatoid arthritis inadequately controlled on Methotrexate.
This was followed by a randomized open-label extension ( OLE ) study with treatment switching which assessed long-term safety, efficacy, pharmacokinetics and immunogenicity.
Patients aged greater than or equal to 18 years with moderate to severe, active rheumatoid arthritis ( 2010 ACR criteria ) for greater than or equal to 3 months and taking Methotrexate for greater than or equal to 3 months ( 10–25 mg/week stable dose for greater than or equal to 8 weeks ) were enrolled.
In the double-blind study, patients were randomized 1:1 to FKB327 or Adalimumab RP ( 40 mg subcutaneously ) every other week with continuing Methotrexate.
The primary endpoint was ACR20 response rate at week 24 with prespecified equivalence margins of −12 to +15% for a two-sided 90% confidence interval ( CI ), recommended by the FDA.
Secondary endpoints included DAS28-CRP at week 24 and ACR20/50/70 response rates over time.
Safety was assessed by the incidence / severity of adverse events and laboratory abnormalities.
In the OLE, patients completing the double-blind study with clinical response and no serious adverse effects were immediately re-randomized to FKB327 or Adalimumab RP so that two-thirds of patients remained on the same treatment as in the study and one-third switched to the alternate treatment ( 40 mg subcutaneously every other week ) for weeks 0–28 ( Part 1 ), then all received FKB327 to week 76 ( Part 2 ).
The primary endpoint was safety.
Interim analysis of the OLE was performed when results of approximately 100 patient-years’ continuous treatment were available on both products.
In the double-blind study, 728 patients from 12 countries were treated with FKB327 ( n=366 ) or Adalimumab RP ( n=362 ).
Demographics and baseline rheumatoid arthritis characteristics were similar between the groups, with mean Methotrexate dose of 15.8 mg/week ( standard deviation [ SD ] 4.8 ) and mean rheumatoid arthritis duration of 8.5 years ( SD 8.0 ).
ACR20 response rate at week 24 ( non-responder imputation, full analysis set ) was comparable ( FKB327 72.5%; Adalilumab RP 74.3% ); 90% CI ( –7.3, 3.6 ) fell within prespecified equivalence margins.
DAS28-CRP at week 24 and ACR20/50/70 response rates over time were highly comparable.
Safety profiles, mean serum trough drug concentration at steady state, and prevalence / titer of anti-drug antibodies ( ADAs ) were all well-matched.
Re-randomization in the OLE resulted in 645 patients receiving the following treatment sequences across the double-blind then OLE ( Part 1 ) studies: FKB327 – FKB327, n=216; Adalimumab RP – Adalimumab RP, n=213; FKB327 – Adalimumab RP, n=108; and Adalimumab RP – FKB327, n=108.
At interim analysis, safety profiles were comparable for all treatment sequences, although group sizes were reduced after switching.
ACR20 response rate at week 30 was comparable after continuous ( FKB327 – FKB327, 82.5%; Adalimumab RP– Adalimumab RP, 84.3% ) and switched ( FKB327 – Adalimumab RP, 86.5%; Adalimumab RP – FKB327, 89.1% ) treatment.
No consistent differences in pharmacokinetics and anti-drug antibodies profiles were seen between continuous and switched treatments.
In conclusion, the double-blind study met its primary equivalency endpoint for ACR20 response rate at week 24; safety, anti-drug antibodies and pharmacokinetics profiles also supported the comparability of FKB327 and Adalimumab RP in patients with active rheumatoid arthritis.
Interim OLE results suggested that long-term safety, efficacy, pharmacokinetics and immunogenicity of FKB327 and Adalimumab RP were comparable on continuous and switched treatment. ( Xagena )
Source: ACR/ARHP Annual Meeting, 2017