Clinical Trials Arena's Abigail Beaney spoke to Robert Barrie and Frankie Fattorinin of Pharmaceutical Technology and GlobalData Insights about the latest developments in rare diseases ahead of Rare Disease Day. The FDA has issued a draft guidance that introduces a new regulatory framework to expedite the development and approval of individualized therapies for patients with ultra-rare diseases where large randomized clinical trials are not possible[1][4]. A framework called the Plausible Mechanism Framework allows for approval based on mechanistic and scientific evidence instead of large studies[1][3]. It includes advanced therapies such as genome editing (eg, CRISPR), RNA-based treatments including antisense oligonucleotides, and others that target specific genetic mutations[1][4]. Efficacy will be demonstrated by multiple lines of evidence, including natural history data, biomarkers, successful target intervention, or improved clinical outcomes[1][3]. The FDA emphasizes the need for robust evidence even in small patient populations[1]. The guideline was announced on Rare Disease Day, 23 February 2026[2][3]. The goal is to support innovation and expand treatment options for patients with rare diseases[1][4].