The pharmokokinetic and pharmacodynamic studies were conducted on normal healthy patients whereas the safety and efficacy study was conducted on rheumatoid arthritis patients, so as to extrapolate the results for various other indications.
Phase 1 Data: Hulio® clinical pharmacokinetics are similar to Adalimumab
A randomized, double-blind, pharmacokinetics study comparing Hulio® with reference adalimumab in 180 healthy subjects found that Hulio® has a similar pharmacokinetic profile to that of reference adalimumab.1
Pharmacokinetic study design1
Randomized, double-blind, parallel-group, single injection study.
180 healthy subjects, aged 18-65 years, were randomized in a 1:1:1 ratio, stratified by bodyweight, to receive a single subcutaneous injection of 40mg/0.8ml of EU-reference adalimumab, US-reference-adalimumab or Hulio® (previously referred to as FKB327).
Pharmacokinetics, local tolerability, immunogenicity and adverse events were assessed prior to and up to 64 days after treatment
The 90% confidence intervals (CI) for the results ratios (Hulio®/reference adalimumab) for average blood adalimumab level over time and maximum adalimumab concentration were within the range 0.80-1.25, indicating bioequivalence.
The tolerability of Hulio® and reference adalimumab was equally acceptable, and there were no differences in safety profile or immunogenicity among the three treatments.
Average serum adalimumab levels measured over 64 days following single injections of Hulio® and reference adalimumab show bioequivalence.1
Hulio® phase III data: Hulio:® Proven clinical efficacy in patients with rheumatoid arthritis (RA)
In the pivotal randomized, double-blind, ARABESC study and open-label extension study, Hulio® was found to have equivalent efficacy to that of the reference drug, reference adalimumab, in RA patients inadequately controlled on methotrexate (MTX).2,3
ARABESC Phase III clinical trial design2
Randomized, double-blind, multi-centre (105 sites in 12 countries), 24-week study.
728 adult patients with moderate-to-severe active RA for at least 3 months, and taking MTX for at least 3 months: mean age 55.3 years; mean DAS28-CRP score 6.1; mean MTX dose 15.7mg/wk.
Patients were randomised in a 1:1 ratio to receive either Hulio® 40mg/0.8ml or reference adalimumab 40mg/0.8ml every other week plus methotrexate.
The primary efficacy endpoint was the ACR20 response rate at Week 24 (defined as a 20 improvement in tender joint count and swollen joint count, and in at least 3 of the other 5 core elements4).
ARABESC Open-Label Extension3
645 participants in ARABESC continued in an open label extension (ARABESC-OLE). This study is ongoing with interim assessment results available at Week 54.
Patients were randomized 2:1 to stay with their original treatment (Hulio® or reference adalimumab) or SWITCH to the alternate treatment.
Results at 24 weeks show that Hulio® and reference adalimumab got similar proportions of patients to achieve ACR20, and the improvement in swollen joint count was similar between the two treatments.
Proportions of patients achieving ACR20 and the mean swollen joint count at Week 24 in patients with RA who received Hulio® or reference adalimumab every other week.
The 95% CIs for the treatment difference (Hulio® – reference adalimumab: -7.6 to 5.0) fell within the prespecified ± 13% margins, demonstrating equivalence.
Equivalence between Hulio® and reference adalimumab was also demonstrated at Week 24 in the following outcomes:2,4
Disease Activity Score in 28 joints plus C-reactive protein level (DAS28-CRP): 3.43 on Hulio;® 3.42 on reference adalimumab
CRP concentration: 10.98 on Hulio;® 11.78 on reference adalimumab
Patient assessment of disease activity: 35.2 on Hulio;® 33.2 on reference adalimumab
Physician assessment of disease activity: 21.5 for both treatments
Patient pain assessment: 34.7 on Hulio;® 33.6 on reference adalimumab
Health Assessment Questionnaire Disability Index: 1.21 on Hulio;® 1.26 on reference adalimumab
Long-term results from the extension study show patients on Hulio® or reference adalimumab do similarly well, even when switching
These results indicate that switching patients from biologic to biosimilar adalimumab, or vice versa, maintains the clinical status of the patients.
Hulio:® proven safety profile in patients with RA
Hulio® and reference adalimumab were demonstrated to have similar safety profiles in the 24-week ARABESC study in patients with RA. The proportions of patients reporting treatment-emergent adverse events (TEAEs) were similar for Hulio® and reference adalimumab (see the table below), and AEs were mainly mild or moderate in severity in both treatment groups. The immunogenicity of Hulio® and reference adalimumab was similar. A summary of the safety profiles for the two adalimumab treatments is given in the table below. For full details of the Hulio® safety profile, please refer to the Summary of Product Characteristics (SmPC).
Summary of Hulio® and reference adalimumab safety profiles from the 24-week ARABESC study in patients with RA.
Patients reporting TEAEs*
Most commonly# reported TEAEs: •Nasopharyngitis •Upper respiratory tract infection
Incidence of serious AEs
Patients reporting active TB
Patients with anti-drug antibodies at final sampling
*TEAEs: treatment-emergent adverse events. #Presenting in at 5% of the patient group.
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▼This medicine is subject to additional monitoring. This will allow quick identification of new safety information. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare providers are asked to report any suspected adverse reactions. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. In order to support effective tracking and traceability of biologics including biosimilars, it is recommended that the brand name and batch number are recorded and used when reporting adverse events.
Puri A, Niewiarowski A, Arai Y, Nomura H, Baird M, Dalrymple I, et al. Pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a new biosimilar medicine of adalimumab, in healthy subjects. Br J Clin Pharmacol 2017; 83(7): 1405-1415.