Global regulatory progress in delivering on the promise of gene therapies for unmet medical needs.

The rapid expansion of the gene therapy pipeline in recent years offers significant potential to treat diseases with great unmet medical need. However, the unique nature of these therapies poses challenges to regulating them within traditional frameworks, even when developing in a single country. Various factors exacerbate the issues in commercializing products across regions, including the lack of established regulatory frameworks for developing gene therapy products in many jurisdictions. While some countries have established separate regulatory frameworks for advanced therapies/regenerative medicine products, differences exist between them. Recommended solutions to overcome these hurdles include fostering convergence among countries with separate regulatory frameworks for these products and utilizing reliance and recognition for countries without such frameworks. Additionally, regulators who choose to establish new dedicated frameworks for regulating gene therapies should consider the inclusion of key elements such as expedited regulatory pathways that offer early engagement with regulators, innovative clinical trial design, and adequate post-market confirmatory studies. Increasing the alignment of regulatory pathways across countries will be crucial to facilitating the development of, and access to, gene therapies on a global scale.

Addressing the Value of Gene Therapy and Enhancing Patient Access to Transformative Treatments.

Although high upfront costs for the high value of gene therapy have resulted in concerns about sufficient reimbursement to allow patient access to these therapies, the significant benefits of gene therapies will not be realized unless patients have access to them. Stakeholders are discussing these issues, and the payment models being developed for the newly approved gene therapies provide an early indication of the flexibility that will be needed from treatment manufacturers, payers, and policy makers to optimize patient access. Maximizing patient access to effective gene therapies is one integral part of the overall mission of the American Society of Gene and Cell Therapy, along with maximizing the quality of therapies and minimizing their costs.

Microfluidic cell sorting by stiffness to examine heterogenic responses of cancer cells to chemotherapy.

Cancers consist of a heterogeneous populations of cells that may respond differently to treatment through drug-resistant sub-populations. The scarcity of these resistant sub-populations makes it challenging to understand how to counter their resistance. We report a label-free microfluidic approach to separate cancer cells treated with chemotherapy into sub-populations enriched in chemoresistant and chemosensitive cells based on the differences in cellular stiffness. The sorting approach enabled analysis of the molecular distinctions between resistant and sensitive cells. Consequently, the role of multiple mechanisms of drug resistance was identified, including decreased sensitivity to apoptosis, enhanced metabolism, and extrusion of drugs, and, for the first time, the role of estrogen receptor in drug resistance of leukemia cells. To validate these findings, several inhibitors for the identified resistance pathways were tested with chemotherapy to increase cytotoxicity sevenfold. Thus, microfluidic sorting can identify molecular mechanisms of drug resistance to examine heterogeneous responses of cancers to therapies.