Advancing ATMPs for orphan diseases: redefining the roles of pharmaceutical companies and academia

Advanced Therapy Medicinal Products (ATMPs), including gene, cell, and tissue-engineered therapies, have transformed the treatment landscape for rare hematologic and immunologic conditions, yet face persistent barriers to market access and sustainability. Although the majority of authorized ATMPs in the EU target orphan diseases, commercial withdrawal and limited patient access remain prevalent. In part these hurdles arose from the fact that most advanced therapies originate in academic settings, where resource and expertise gaps hamper regulatory navigation, manufacturing standardization, and clinical translation, especially for ultra-rare diseases with low prevalence. The ongoing emergence of new models of commercialization, such as of charitable foundations, public benefit corporations, and international consortia, offers new approaches to sustain post-approval access. Concurrent EU regulatory initiatives—Joint Clinical Assessments, managed entry agreements, flexible trial designs—are streamlining evidence generation and harmonizing reimbursement frameworks, but long-term economic and operational sustainability remain a challenge. Building on approved but struggling gene therapies for immune deficiencies, this review synthesizes evolving strategies across policy, regulation, and innovation, highlighting the need for coordinated multi-stakeholder action. Ensuring sustained access to effective gene therapies for patients with rare immune deficiencies will require aligned efforts from clinicians, academic innovators, regulators, payers, and patient advocates, as well as adaptive funding models. The lessons from academic and charitable stewardship of gene therapies may chart new pathways for the successful translation and retention of orphan ATMPs in clinical practice.