Auto-Injector for Biosimilar Etanercept Equivalent in Dosing, Tolerability to Pre-Filled Syringe

A study published in the British Journal of Clinical Pharmacology demonstrated the bioequivalence of GP2015, a biosimilar etanercept treatment (Sandoz’s Erelzi), when delivered with an auto-injector (AI) and when delivered with a pre-filled syringe (PFS) in patients across a variety of body weights.

According to the study’s authors, patients with rheumatoid arthritis (RA) may have difficulty self-administering pre-filled syringes due to the impact of RA on their dexterity, and may demonstrate greater adherence to therapy if provided with modes of administration that are convenient and easy to use. In June, Sandoz received approval from the European Commission (EC) for Erelzi, which is available in both the AI and PFS delivery devices. Sandoz announced that the product is now available to patients in Canada, where it is also sold in AI and PFS devices.

The study, which was conducted in healthy volunteers, compared PK in subjects who comprised a range of body weights. Secondary objectives of the study included comparison of additional PK parameters between the AI and PFS as well as the safety and tolerability of GP2015.

The study was designed as an open-label, randomized, 2-way, crossover study with 2 treatment periods. The subjects (n = 51) were healthy adult men who ranged in weight from 50 kg to 99.9 kg, and ranged in body mass index from 19.0 to 29.9. The subjects were randomized to receive a single, 50-mg subcutaneous injection of GP2015 via either AI or PFS during the first treatment period. After a wash-out period of 35 days or more, subjects received a single, 50-mg subcutaneous injection of GP2015 via either AI or PFS, whichever delivery method was the opposite of the first treatment period’s method. Twenty-five subjects were randomized to first receive AI dosing, and then to receive PFS dosing; 26 patients were randomized to first receive PFS, then AI. Outpatient visits were conducted up to day 19 to assess PK and safety. A follow-up visit was conducted 28 days after the second product administration. Two subjects did not complete the study (1 due to a protocol violation and 1 due to an adverse event).

Mean serum concentration-time profiles were found to be similar between the AI and PFS treatment administrations. C_max, AUC_0—tlast, and AUC_0—inf were also found to be similar; the 90% confidence intervals for all 3 values were within the predefined bioequivalence range of 0.80 to 1.25. Furthermore, serum concentrations were similar across body weight categories, and the treatment’s half-life was identical (109 hours) between both administrations.

Incidence of treatment emergent adverse events (TEAEs) was identical between the study arms, the most frequently reported being headache, neutropenia, and rhinitis. Three subjects had mild injection-site reactions. All TEAEs were considered mild, and resolved during the study period.

The researchers concluded that AI and PFS deliver biosimilar etanercept in an equivalent way, and suggest that AI and PFS can be used interchangeably. The authors also note that no difference was observed in AI and PFS delivery across different weight groups, suggesting that both devices can be used in subjects with varying thickness of subcutaneous adipose tissue. The AI device, the researchers said, could offer advantages in terms of ease and convenience of use for patients across a range of body weights.