The pharmaceutical industry must adjust its development and regulation models to unlock the true potential of gene therapy

Over the past few years, the promise of curative gene therapies for rare disease has started to become a reality.

This is due to improved clinical and scientific understanding of safety profiles and enhanced manufacturing processes. In 2018, more than 150 new drug applications were filed for gene therapy and this is expected to increase in 2019.

The majority of the gene therapy pipeline in 2019 is focused on monogenic rare diseases, primarily oncology. Small populations of patients with these diseases have generally not responded sufficiently to more “traditional” therapeutics such as monoclonal antibodies, therefore, there is a higher demand, making them optimal targets for gene therapy. This “high unmet need” has led to regulatory authorities enabling faster approvals via an accelerated regulatory review pathway. For example, the clinical trial model has been shifted from Phase I, II, III trials into Phase I, Phase II/III, and confirmatory Phase III trials after approval. However, there are many challenges facing the pharmaceutical industry before the true potential of gene therapy can be realised in a safe and efficient way.

“These products are initially being aimed at devastating diseases, many of which are fatal and lack available therapy. In these settings, we’ve traditionally been willing to accept more uncertainty to facilitate timely access to promising therapies.”

The uncertainty comes in many forms. The biggest challenge is market access. More traditional medicines such as monoclonal antibodies will soon have biosimilar competition leading to reduced costs, therefore novel gene therapies will need to demonstrate cost-effectiveness, which may require changes to the healthcare ecosystem, involving multiple stakeholders. Furthermore, due to the accelerated regulatory approvals, long term safety and efficacy have not been fully established. This would require further time and research to ensure these medicines are safe as well as effective. Demonstrating the safety, quality and potency of the final product has been a major manufacturing challenge. For example, the presence of foreign DNA after purification has led to some clinical trial suspensions.

Clinical development organisations will need to invest in patient registries, confirmatory trials and utility of real-world data to adjust to the tightened clinical trial timelines and initiate long term follow-up, ensuring safety and efficacy of the product. Regulatory bodies will need to take strides to expand regulatory review capacity for gene therapy. The FDA is hiring additional reviewers and released a draft guidance which should help with approvals for pharmaceutical companies. Due to the ever-evolving realm of gene therapy, regulatory challenges will continue. Regulatory and ethical frameworks will need to evolve to keep up with the complex science associated with these treatments.