Efanesoctocog alfa (Altuvoct; BIVV001) is a fusion protein comprising domains of (i) factor VIII, (ii) the von Willebrand factor, and (iii) IgG1 coupled to two polypeptide linkers. The half-life of efanesoctocog alfa in plasma is about 40 h. The polypeptide linkers are released by thrombin activation, resulting in an active form of efanesoctocog alfa that results in the formation of a fibrin clot. Data from two single-arm ongoing studies were submitted: the XTEND-1 study enrolled 159 subjects aged 12–72 years, and the XTEND-kids study enrolled 74 subjects aged <12 years; all subjects had severe haemophilia A. Single-arm studies are not amenable to conventional statistical analysis of ‘effect of cause’, and so a supplementary analysis was conducted on the basis of ‘cause of effect’, making use of the scheme described by Toulmin coupled to an analysis of causal inference. Overall, the claim that Altuvoct is indicated to treat people aged ≥2 years with severe (and moderate) haemophilia A was considered to be supported by the results of the submitted studies and associated modelling exercises; the benefit–risk evaluation of Altuvoct was found to be positive in the target population.

In November 2024, a two-day meeting entitled “PBBM—Best Scientific Practices to Define Drug Product Performance: Latest Regulatory and Industry Perspectives” was organised by the Academy of Pharmaceutical Sciences Biopharmaceutics Focus group and hosted by MHRA in London, UK. Physiologically based biopharmaceutics modelling, referred to as PBBM, is used to inform drug product quality strategies and provide a more detailed understanding of how medicines can interact with the human body. Industrial, academic, regulatory, and software company scientists came together to discuss the latest developments in PBBM and to debate key topics relevant to the establishment of best practices and improved implementation. Case study presentations and breakout sessions highlighted how companies are using PBBM in their portfolio decision-making (early development through post-approval changes). Discussions highlighted how the exploration of drug product quality risks has evolved over time, moving from the more empirical BCS classification approach to a more detailed in vivo and mechanistic understanding, where sponsors have and continue to invest in building clinical drug product knowledge. Regulatory scientists shared how they are building experience in using PBBM to set clinically relevant drug product quality specifications, including how they would like to see the area grow in the future. Although significant progress has certainly been made in this field over the last 10 years, the need to continue to bring industry and regulators closer together in the future remains a key topic. Guideline evolution, training and continued dialogue will be essential in reaching a harmonised approach to the use of PBBM to develop drug product strategies and set quality specifications.