The year 2025 is marked as a "breakthrough year" for biotechnologies targeting rare diseases[1]. Full drug pipelines and growing revenues are driving these biotechs to transform into more mature global biopharmaceutical companies[1]. Rare disease developers point to cashflow and R&D expansion as evidence of a transition from upstart biotech firms to established companies after strong results in 2025[1]. Several rare disease biotech firms have identified commercial success in 2025 as a key point for the sector to mature[1]. Alnylam projects sales of up to $5.3 billion in 2026, of which $4.7 billion is expected to come from the sale of Amvuttra and Onpattro to ATTR[1]. Ultragenyx expects two approvals in 2026 – for gene therapies UX111 for Sanfilippo syndrome and DTX401 for glycogen storage disease[1]. In September 2025, the FDA implemented the Rare Disease Evidence Principles (RDEP) framework for approving therapies based on a single study without a control group, and on January 12, 2026, it relaxed manufacturing requirements for cell and gene therapies for unmet needs[1].