Spinal Muscular Atrophy (SMA) is a progressive monogenic neurologic disease caused by bi-allelic deletion or mutation in the survival motor neuron 1 (SMN1) gene, resulting in the irreversible loss of motor neurons. Patients with SMA develop motor neuron loss, muscle weakness, respiratory failure, and are frequently hospitalized early in life. Furthermore, SMA is associated with a poor quality of life, significant caregiver burden, and early mortality. Novel gene therapies for ultra-rare diseases such as SMA attempt to address the genetic root cause of the disease. Gene therapy (GT) for SMA is designed for sustained expression of SMN protein allowing for rapid onset and durable therapeutic effect since it targets non-dividing neurons. However, these kinds of therapies require medical and payer education and different evaluation and valuation approaches compared to conventional pharmaceuticals; and new valuation models and philosophies are needed to harness the high pace of innovation. The evaluation and valuation of gene therapy for rare conditions with a large unmet need are probably amongst the most challenging decisions that medical and Health Technology Assessment (HTA) bodies currently face and the lack of standardized evaluation methodologies for GTs provide challenges and require innovative solutions. This panel will address different approaches to clinical and economic data collection and evaluation.