Relative Bioavailability of a Single Dose of Belimumab Administered Subcutaneously by Prefilled Syringe or Autoinjector in Healthy Subjects

Abstract

Intravenous belimumab is approved for the treatment of systemic lupus erythematosus; subcutaneous self‐administration would enable greater patient access. This study assessed relative bioavailability, tolerability, and safety of 1 subcutaneous dose of self‐administered belimumab by healthy subjects using a single‐use autoinjector or prefilled syringe. Subjects (randomized 1:1:1:1) self‐administered belimumab 200 mg subcutaneously (abdomen or thigh) by prefilled syringe or autoinjector. Pharmacokinetics, adverse events (AEs), injection‐site pain, and administration errors were recorded. Of 81 subjects, 5 experienced administration errors and were excluded from pharmacokinetic analyses. Mean serum belimumab concentration profiles were similar for both devices, with a weak trend toward higher concentrations for thigh injection compared with abdominal injections. Maximum observed serum concentration was slightly higher with the autoinjector (27.0 vs 25.3 µg/mL) and area under the concentration–time curve slightly lower (701 vs 735 day · μg/mL), compared with the prefilled syringe. Incidence of AEs was 51% (41 of 81 subjects; headache was most common), with no serious or severe AEs. Median injection‐site pain scores were low (0 after 1 hour). Device handling was reported as acceptable by ≥95% of autoinjector users and ≥90% of prefilled syringe users for each characteristic assessed. These results support the use of either device for belimumab subcutaneous administration.

Evaluation of a novel autoinjector for subcutaneous self-administration of belimumab in systemic lupus erythematosus

“…Patients with active SLE demonstrated a good level of usability and reliability with the autoinjector, confirming results of a previous study conducted in healthy subjects [15]. The majority of injection failures was due to user error, which were rectified with additional training and slight adjustments in user instructions.…”

“…Therefore, the PK results from this study support a 1 – 4-week interval for switching between belimumab IV and belimumab SC. In addition, the stable transition from IV to SC dosing demonstrated here supports the use of the prefilled syringe for administration of belimumab SC as bioequivalent exposures have been demonstrated for belimumab SC administration using the autoinjector and the prefilled syringe [15]. The 200-mg dose was selected based on previous analyses that showed that weekly belimumab 200 mg SC would achieve similar steady-state belimumab exposures to that of monthly belimumab 10 mg/kg IV [16].…”

“…A novel single-use autoinjector has been developed for SC delivery of belimumab. In a single-dose study of healthy volunteers, the autoinjector demonstrated good usability, reliability, and safety following self-administration [15]. Four weekly doses of belimumab 200 mg SC were well tolerated in healthy volunteers, and it was predicted that weekly administration would achieve exposures comparable to the approved IV dosing regimen [16].…”

Efficacy and Safety of Subcutaneous Belimumab in Systemic Lupus Erythematosus: A Fifty‐Two–Week Randomized, Double‐Blind, Placebo‐Controlled Study

“…A liquid formulation of belimumab has been developed, along with a prefilled syringe and an autoinjector device for administering belimumab SC. In a single‐dose study, healthy volunteers self‐administered belimumab 200 mg SC using the prefilled syringe or the autoinjector device; both injection devices demonstrated good usability, reliability, and safety . The 200 mg SC dose was selected in order to achieve a target belimumab steady‐state area under the curve exposure following SC administration similar to that obtained with 10 mg/kg IV every 4 weeks .…”

Efficacy and Safety of Subcutaneous Belimumab in Anti–Double‐Stranded DNA–Positive, Hypocomplementemic Patients With Systemic Lupus Erythematosus

“…The development of a novel liquid formulation of belimumab, along with a prefilled syringe and autoinjector device, enables patients to self-administer subcutaneous (SC) belimumab, an option demonstrated as preferable to IV administration by the majority of individuals (12). Single-and multi-dose studies of self-administered SC belimumab 200 mg have demonstrated that both the prefilled syringe and autoinjector devices show good usability, reliability, and safety (13,14). Furthermore, administration of weekly SC belimumab 200 mg achieved a target belimumab steady-state exposure similar to that obtained with IV belimumab 10 mg/kg every 4 weeks (15,16).…”