Mitigating the Unmet Needs of Hemophilia Patients: A Case Study of the Development Strategy Behind a Novel siRNA Hemophilia Combination Medical Device.

Abstract

The purpose of this case study is to discuss the strategy behind the selection and development of a novel combination medical device to treat hemophilia patients in order to improve treatment for all segments of the hemophilia community leading to overall better patient outcomes. Replacement therapy of the necessary missing clotting factors is the current standard of care, but involves repeated prophylactic intravenous infusions. Fitusiran is a siRNA therapeutic designed to treat hemophilia patients by reducing expression of antithrombin (AT) in order to indirectly restore normal homeostasis. Its pharmacokinetic profile enables it to be dosed subcutaneously at monthly intervals, while maintaining a consistent level of plasma AT levels. Combined with a fixed low injection volume for all adolescent and adult patients, fitusiran is an ideal candidate to utilize an autoinjection device. Both of these features are expected to increase therapeutic adherence and improve patient health. To advance a combination device for approval, regulatory agencies require documentation of the device development process. The User Needs Assessment and consideration of regulatory standards on medical devices and human factors were used to develop the fitusiran device User Requirements document and inform the design of the device platform. Based on established dosing and viscosity criteria and human factors/user needs assessments, the SHL Molly device was selected for delivery of fitusiran. Although Alnylam has improved their understanding of the hemophilia patient population’s needs, there are still uncertainties about the selected Molly device’s compatibility with fitusiran. In addition, because Alnylam was continuing to establish their siRNA platform while developing fitusiran, this led to certain inefficiencies in the process and necessitated an expedited approach to developing a device for fitusiran in order to position it for a successful launch. Through this device development process, Alnylam can utilize its learnings in device development for future programs.