Patient-Centric Development of a Low-Volume, Low-Viscosity, Once Every 4 Weeks (Q4W) Autoinjector Combination Product for Povetacicept
Biologic therapies delivered subcutaneously (SC) are increasingly moving toward at-home self-administration using drug-device combination products. This shift places greater emphasis on the patient experience, and factors such as dose volume, injection time, dosing frequency, viscosity, injection force, and ease of use can affect treatment burden. This article focuses on the impact of balancing high protein concentration with low viscosity during drug product formulation development for an improved patient experience for povetacicept, an investigational, subcutaneously administered dual B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) inhibitor being developed for the treatment of multiple kidney diseases, including IgA nephropathy (IgAN). For povetacicept, formulation and device considerations were integrated throughout development. Studies evaluated protein concentration, dose volume, viscosity, injection force, injection time, and usability, in addition to standard stability, to develop a low-volume Q4W autoinjector. The selected 175 mg/mL formulation delivers an 80 mg dose in 0.46 mL. The viscosity was no more than 10 cP at 15-25{degrees}C and in a 1 mL prefilled syringe, the average glide force was 6 N, and the injection time at a constant force of 20 N was < 2 seconds. The same prefilled syringe was incorporated into an autoinjector with an injection time of less than 2 seconds in air. We conducted a limited assessment of an approved treatment for IgAN (Voyxact) administered via prefilled syringe (PFS) for effects of viscosity, fill volume and syringe configuration under the same experimental conditions. The viscosity at room temperature was 16 cP, with an average glide force of 27N and injection time of 19 seconds for the 2 mL dose. In conclusion, povetacicept was designed to support convenient and user-friendly at-home self-administration through Q4W dosing, a low injection volume, a low viscosity formulation, rapid delivery, and an easy-to-use autoinjector. This integrated formulation and device development approach demonstrates how patient-centric considerations can be incorporated in combination product development. Together, these attributes have the potential to reduce the practical burden associated with repeated, long-term treatment for IgAN patients.