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CT-P17 (Celltrion, Inc., Incheon, Republic of Korea) is a biosimilar of reference adalimumab (Humira®; AbbVie Inc., North Chicago, IL, USA), which has recently received regulatory approval from the European Medicines Agency. This analysis was designed to evaluate the stability profile of CT-P17 compared with reference adalimumab and the currently licensed adalimumab biosimilars ABP 501 (Amjevita®/Amgevita®; Amgen Inc., Thousand Oaks, CA, USA) and SB5 (Imraldi®; Biogen Inc., Cambridge, MA, USA) when stored at low temperature (5 °C) or room temperature (25 °C) with 60% relative humidity for up to 28 days. Multiple orthogonal and complementary tests demonstrated that CT-P17 was stable for 28 days under all tested conditions, as well as for protein concentrations tested (50 vs 100 mg/mL), type of delivery device (autoinjector vs prefilled syringe), and manufacturing date (recently manufactured vs aged for 17 months). There were slight differences among products in terms of charge variants, oxidation level, purity, and number of subvisible particles; however, overall, the quality of each product was maintained over 28 days. Our data suggest that CT-P17 may be used without any significant loss of stability when stored at 5 °C or 25 °C with 60% relative humidity for up to 28 days, and was not impacted by protein concentration tested and delivery device. Comparative stability data suggest that the appropriate maximum storage period for CT-P17 may be up to 28 days at room temperature with 60% relative humidity.

Introduction Etrolizumab is a novel, dual-action, anti-β7 integrin antibody in development for patients with moderate to severe ulcerative colitis or Crohn’s disease. Phase 3 studies use a prefilled syringe (PFS) for etrolizumab administration. In parallel, an autoinjector (AI) is being developed to increase delivery options for patients if etrolizumab is approved. Here we describe the overall development strategy and detail the first-in-human study of this AI. Methods This open-label study of healthy volunteers evaluated the tolerability and usability of the etrolizumab AI under development. The primary endpoint was the proportion of participants with greater than mild pain following injection. Adverse events (AEs) and usage errors were also assessed. Results were reported by injection site (thigh vs abdomen) and needle training (experienced vs naive). Pharmacokinetic (PK) variability between participants was an exploratory endpoint. Results Thirty participants completed the study; 97% of them did not experience any pain greater than mild, and 50% did not experience any pain at all. Three usage errors were observed, one of which resulted in delivery of a partial dose of etrolizumab. No patterns of usage errors were observed. Mild injection site reactions (ISRs) were reported; all resolved by the end of the study. Participants injecting into the abdomen reported more ISRs than those injecting into the thigh; needle training did not influence AE incidence or severity. Conclusions Results from this first-in-human study demonstrate that single injections of etrolizumab 105 mg using an AI were well tolerated in healthy volunteers, with transient, mild pain and minimal usage errors. Results from this study also informed the design of a subsequent PK comparability study evaluating exposure of etrolizumab administered by either the PFS or the AI. Overall, the availability of an AI may provide an attractive option for patients desiring a convenient, easy-to-use delivery mechanism for etrolizumab. Trial Registration NCT02629744 Electronic supplementary material The online version of this article (10.1007/s12325-021-01651-8) contains supplementary material, which is available to authorized users.

Introduction Etrolizumab is a novel, dual-action anti-β7 integrin antibody studied in phase 3 trials in patients with inflammatory bowel disease. An autoinjector (AI) is being developed in parallel to complement the prefilled syringe with needle safety device (PFS-NSD) for subcutaneous (SC) administration in these trials. Here we demonstrate the comparable pharmacokinetics, tolerability, and safety of both devices. Methods This randomized, open-label, two-part study in healthy participants evaluated the comparability of etrolizumab exposure between the AI and the PFS-NSD. Part 1 (pilot) involved a small number of participants, and initial results were used to finalize the design of the larger part 2 (pivotal) study. In both parts, participants were randomly assigned to receive a single SC dose of etrolizumab 105 mg by AI or PFS-NSD. Randomization was stratified by body weight. Primary pharmacokinetic outcomes were Cmax, AUClast, and AUC0–inf. Results One hundred and eighty healthy participants (part 1, n = 30; part 2, n = 150) received a single SC dose of etrolizumab by AI or PFS-NSD. Primary pharmacokinetic results from part 1 supported modification of the part 2 study design. Results from part 2 demonstrated that etrolizumab exposure was equivalent between devices, with geometric mean ratios (GMRs) between AI and PFS-NSD of 102% (90% confidence interval [CI] 94.2–111) for Cmax, 98.0% (90% CI 89.3–107) for AUClast, and 97.6% (90% CI 88.6–107) for AUC0–inf. Median tmax and mean terminal t1/2 were also similar between devices. GMRs and 90% CIs of all primary pharmacokinetic parameters were fully contained within the predefined equivalence limits (80–125%). Conclusion This pharmacokinetic study demonstrated that single SC injections of etrolizumab 105 mg using an AI or a PFS-NSD resulted in equivalent etrolizumab exposure and similar safety and tolerability in healthy participants. Taken together, these results support the use of an AI for etrolizumab administration. Trial Registration NCT02996019.

This study aimed to compare the usability of subcutaneous administration of SB4 (an etanercept biosimilar) via prefilled syringe (PFS) and autoinjector (AI) based on injection site pain, patient preference, and safety in patients with rheumatoid arthritis (RA). This was an open-label, single-arm, multicenter study to evaluate the usability and safety of the AI and PFS of SB4. Adult patients with RA received two injections of SB4 via the PFS, followed by six injections by the AI every week, up to 8 weeks. The primary endpoint was the change in injection site pain score immediately post-injection from week 1 (PFS) to week 3 (AI). Injection site pain after 15–30 min post-injection, overall impression, and preference for PFS and AI were also assessed. Safety was assessed up to 11 weeks after the first injection. A total of 54 patients were enrolled and 52 patients (96.3%) completed the 8-week treatment period. The mean difference in pain scores between PFS and AI was − 0.057 and the 95% CI of the difference was [− 0.63, 0.51], which was within the equivalence margin of ± 5. Overall impression of the device slightly favored the AI. Overall preference for the AI was more favorable when compared to the PFS in all categories. Adverse events were mild to moderate and found to be generally consistent with those expected for reference etanercept. There were no deaths or serious adverse events reported. This study demonstrated comparable usability and safety between the PFS and AI when self-administrated by patients with RA. ClinicalTrials.gov identifier, NCT03193957. Samsung Bioepis.

Introduction Brenzys was developed as an etanercept biosimilar of Enbrel. The aim of this study was to assess preference and perceived ease of use for the new Brenzys autoinjector compared to the currently available marketed Enbrel MYCLIC autoinjector (Australia) and Enbrel SureClick autoinjector (Canada) for the treatment of rheumatoid arthritis (RA). Because RA affects manual dexterity, ease of use of an autoinjector is a particularly important consideration in developing effective self-delivery of long-term courses of therapy. Methods Patients (N = 191) reporting a diagnosis of RA and nurses and rheumatologists (N = 90) with experience managing RA were shown how to use Brenzys and Enbrel autoinjectors (in counterbalanced order between participants), then they used each autoinjector by injecting into a pad simulating skin, and completed a questionnaire. Study sessions took place in Australia and Canada. Results A binomial test showed that significantly more patients indicated that the Brenzys autoinjector was easier to use than the Enbrel autoinjector (79% reporting Brenzys easier to use; p

Interferon (IFN) beta-1b was the first disease-modifying therapy to be approved for the treatment of multiple sclerosis (MS), and over 21 years of follow-up data demonstrate its efficacy and long-term safety profile. Following recent regulatory approvals in the USA and European Union, IFN beta-1b is now one of the seven disease-modifying therapies [intramuscular IFN beta-1a; subcutaneous (SC) IFN beta-1a; IFN beta-1b SC; glatiramer acetate SC; oral dimethyl fumarate; oral teriflunomide; and intravenous alemtuzumab] indicated for first-line use in relapsing–remitting MS. Here we review the clinical trial and follow-up data for IFN beta-1b and discuss factors that clinicians may consider when selecting this treatment, both at first line in early MS, and later in the disease course. Electronic supplementary material The online version of this article (doi:10.1007/s12325-014-0149-1) contains supplementary material, which is available to authorized users.

Introduction The purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs. Methods Two independently conducted simulated-use studies, with no active drug administered, quantified use errors and evaluated the abatacept autoinjector and competitor devices on key attributes (comfort, control, ease of use, confidence of dose) and overall acceptability. Autoinjector preference was also assessed. Participants were patients with rheumatoid arthritis, caregivers, and healthcare professionals (HCPs). Participants were informed that a new rheumatoid arthritis autoinjector was being tested but were blinded to the intended drug and sponsor identity. Results In the formative (pre-validation) study (n = 54), two high-priority use errors occurred, both of which resulted from protocol non-compliance rather than mental confusion or physical limitations. In the summative (validation) study (n = 99), one high-priority use error occurred; this was deemed a simulated-use study artifact as participant behavior was guided by actual experience associated with the feel of drug delivery into the skin rather than by protocol, so no mitigation steps were considered necessary. Across user groups, average scores were consistently high for the pre-defined key attributes. Overall acceptability scores (7-point scale) were significantly higher for the abatacept versus competitor autoinjectors—formative study: patients 6.7 vs 5.2 (P = 0.0001), caregivers 7.0 vs 4.6 (P = 0.0093), HCPs 6.8 vs 5.1 (P = 0.0020); summative study: patients 6.5 vs 5.9 (P = 0.0404), caregivers 6.8 vs 5.8 (P = 0.0047), HCPs 6.8 vs 5.1 (P = 0.0002). The abatacept autoinjector was preferred to competitor devices: patients 85.7% vs 14.3% (P = 0.00002), caregivers 84.2% vs 15.8% (P = 0.00443), HCPs 95.0% vs 5.0% (P = 0.00004). Positive experiences with the abatacept autoinjector were attributed to the rubberized grip, device size, visualization of dose progression, button ergonomics, and ease of use. Conclusion The abatacept autoinjector demonstrated usability without patterns of preventable use errors, and with high acceptability ratings across all key attributes assessed. Preference over competitor autoinjectors was due to device ergonomics, visualization of dose progression, confidence of dose delivery, and overall ease of use. Funding Bristol-Myers Squibb. Electronic supplementary material The online version of this article (doi:10.1007/s12325-016-0286-9) contains supplementary material, which is available to authorized users.