A Randomized, Open-Label Study Conducted to Evaluate the Bioequivalence of Pegfilgrastim-cbqv On-Body Injector Versus Prefilled Syringe in Healthy Male Participants.

INTRODUCTION: To help prevent febrile neutropenia, pegfilgrastim-cbqv (UDENYCA®; Coherus BioSciences), a pegfilgrastim (NEULASTA®; Amgen) biosimilar, is administered 24-96 h after myelosuppressive chemotherapy. Delivery of pegfilgrastim-cbqv using an on-body injector (OBI) provides an alternative method of administration, affording options in drug delivery. This study aimed to establish pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence and assess the safety of pegfilgrastim-cbqv administered using an OBI compared with a prefilled syringe (PFS). METHODS: In this open-label, two-period crossover study, healthy adult male participants (N = 189) were randomly assigned 1:1 to receive pegfilgrastim-cbqv 6 mg subcutaneously using an OBI (n = 92) or a PFS (n = 95) in period 1 and then an injection via the other method in period 2. Primary PK end points were area under the concentration-time curve from time 0 to infinity, area under the concentration-time curve from time 0 to the last quantifiable concentration, and maximum plasma concentration. Secondary PD end points, safety, immunogenicity, and tolerability were also assessed. RESULTS: The 90% confidence intervals (CIs) of the geometric mean ratios for the PK and PD end points fell within the predetermined range (80-125%), indicating PK and PD bioequivalence between pegfilgrastim-cbqv OBI and pegfilgrastim-cbqv PFS. Treatment-emergent adverse events (TEAEs) occurred in 87.8% and 75.8% of participants in the OBI and PFS groups, respectively. Most TEAEs were musculoskeletal effects. The most common OBI-related TEAE was injection site erythema (31.7%), which was mild, transient, and self-limiting. The incidence of treatment-emergent antidrug antibodies (ADAs) was similar between the OBI and PFS. ADAs had no apparent impact on PK, PD, or safety. Neutralizing antibodies were not detected in any participant. CONCLUSIONS: Results of the study showed PK and PD bioequivalence of pegfilgrastim-cbqv administered using OBI compared with PFS. OBI and PFS administration had similar safety, tolerability, and immunogenicity profiles. No unexpected safety signals were identified. Graphical Abstract available for this article.

Febrile neutropenia is when a patient has a fever and a lower-than-normal number of white blood cells. When white blood cell counts are low, patients are more susceptible to opportunistic infections as a result of their weakened immune systems. Severe febrile neutropenia can lead to the stopping or delaying of chemotherapy. The drug pegfilgrastim-cbqv is used 24­96 h after chemotherapy to stimulate the growth of white blood cells. Pegfilgrastim-cbqv is available in a single-dose prefilled syringe and in a prefilled autoinjector. If a patient cannot inject themselves with the drug, they must go to a clinic for the injection. Using an on-body injector applied to the skin that automatically injects the drug at a specific time could eliminate the need to go to the clinic. During this study, healthy adult male participants were given pegfilgrastim-cbqv through an on-body injector or a prefilled syringe to investigate if the movement of the drug into, through, and out of the body (pharmacokinetics) and the physiological action of the drug in the body (pharmacodynamics) were similar between the two injection methods. Side effects were also studied. The researchers found that the pharmacokinetics and pharmacodynamics for pegfilgrastim-cbqv given by on-body-injector or prefilled syringe were similar. The number and types of side effects were also similar. The most common side effect for the on-body injector was mild erythema at the injection site. This side effect resolved by itself. The treatment benefit and safety of pegfilgrastim-cbqv were very similar regardless of how the drug was administered.

Pharmacokinetic and Pharmacodynamic Bioequivalence of Pegfilgrastim-cbqv Delivered via a Prefilled Autoinjector and Prefilled Syringe in Healthy Male Participants.

INTRODUCTION: Pegfilgrastim-cbqv (UDENYCA®; Coherus BioSciences, Redwood City, CA, USA) is a pegfilgrastim (Neulasta®; Amgen, Thousand Oaks, CA, USA) biosimilar approved for administration by prefilled syringe (PFS). The recently approved pegfilgrastim-cbqv prefilled autoinjector (AI) was developed as another method of self-administration and to aid in-office use, providing flexibility in drug delivery. The objectives of the study were to assess the pharmacokinetics (PK) and pharmacodynamics (PD) to determine bioequivalence of the prefilled AI and the PFS for administration of pegfilgrastim-cbqv and to assess the safety profile of the prefilled AI. METHODS: During this open-label, two-period crossover study, healthy adult males (N = 155) were randomly assigned (1:1 ratio) to receive a subcutaneous injection of pegfilgrastim-cbqv using a prefilled AI (n = 76) or a PFS (n = 79) in period 1. During period 2, participants received an injection using the other method. Primary PK and secondary PD parameters were calculated to assess the bioequivalence of the treatment as administered by the two delivery methods. Safety and immunogenicity were also assessed. RESULTS: The 90% CIs of the geometric mean ratios for the PK and PD parameters were within the required range (80-125%), demonstrating bioequivalence between the pegfilgrastim-cbqv prefilled AI and PFS. Treatment-emergent adverse events (TEAEs) were reported by 75% and 74.1% of participants in the prefilled AI and PFS groups, respectively. The most common TEAEs in both treatment groups were myalgia, bone pain, and headache. AI-device-related TEAEs were injection site pain (1.4%) and injection site bruising (0.7%). The incidence of antidrug antibodies and neutralizing antibodies was low and was similar in both treatment sequences. CONCLUSIONS: The bioequivalence of pegfilgrastim-cbqv administered using a prefilled AI and a PFS was established. The safety, including immunogenicity profiles, of pegfilgrastim-cbqv administered using the prefilled AI and the PFS were similar, with no new safety findings.

Pegfilgrastim-cbqv is used 24­96 h after chemotherapy to prevent febrile neutropenia. This is when a patient has a fever and a lower-than-normal number of white blood cells. Pegfilgrastim-cbqv is also used to treat someone who has a fever and a low number of white blood cells after high radiation exposure (hematopoietic acute radiation syndrome). Pegfilgrastim-cbqv is given as an injection by hand. The syringe is already filled with the drug. The US Food and Drug Administration also approved a prefilled autoinjector as another way to give the drug. The autoinjector is a spring-loaded system that delivers pegfilgrastim-cbqv in less than 10 s. A shield covers the needle before and after the drug is given. The autoinjector is safe and effective for patients to give pegfilgrastim-cbqv to themselves and for health care staff to use in-office. This study looked at whether the way in which pegfilgrastim-cbqv moves through the body (pharmacokinetics) and its effects on the body (pharmacodynamics) were similar in healthy adult males when using a prefilled autoinjector and a prefilled syringe. Side effects were also assessed. The two administration methods had very similar pharmacokinetic and pharmacodynamic results for pegfilgrastim-cbqv. The side effects for both groups were also similar. The most common side effects were muscle aches and pains, bone pain, and headaches. Giving pegfilgrastim-cbqv with the prefilled autoinjector was very similar to giving it with the prefilled syringe and the pharmacokinetics, pharmacodynamics, and safety were similar.