Blog April 13, 2020

FDA Finalizes Gene Therapy Guidelines and Adds New Draft Guidance on Orphan Drug Exclusivity

fda geneGene therapy has come a long way since 1972, when researchers publishing in the journal Science first suggested this approach might someday provide a means of treating genetic disorders. While research was held back for several years following a patient death in 1999 and other adverse events in the early 2000s, today the field of gene and cell therapy is flourishing.

Four gene therapies have now achieved FDA approval, and close to 1,000 INDs are open, covering a variety of clinical trials. By 2025, the FDA expects to be reviewing and potentially approving 10-20 cell and gene therapies a year. In addition to challenges posed by the sheer volume of INDs, the agency’s review of potentially “one-and-done” gene and cell therapy products is likely to be more complex than for traditional drugs. The FDA’s Center for Biologics Evaluation and Research notes that the technology poses unique challenges to the assessment of gene and cell therapy products’ efficacy and safety, especially regarding durability of response and long-term safety.

In 2018, the agency issued six draft guidelines covering various aspects of gene and cell therapy development. These documents covered elements of the manufacturing and quality controls sections of gene therapy INDs, retroviral safety testing, and guidelines specific to the development of treatments for rare diseases, retinal disorders and hemophilia. In late January, these six documents were finalized, creating a regulatory framework that provides meaningful guidance for developers as they design and develop gene and cell therapy products. At the same time, the new guidelines acknowledge that the durability of the treatment response cannot be fully answered in clinical trials and that the FDA needs to accommodate a level of uncertainty around long-term responses in its reviews.

In addition to finalizing the six draft guidelines, the agency issued one new draft guideline for public review and comment, addressing how the agency would decide on awarding orphan drug exclusivity if two gene therapy products were intended for the same medical indication. As two gene therapies addressing the same target and desired therapeutic outcome could potentially be deemed virtually identical, such a finding could prevent the second one from gaining approval for the same indication during the seven years of orphan exclusivity unless shown to be clinically superior.

Thus, the agency is proposing to establish “sameness” between therapies on the basis of both transgenes and viral vectors employed. Products using different transgenes for the same disease, whether or not the vectors are the same, would be regarded as distinct therapeutics. Those using the same transgenes, but different vectors, would also be regarded as different drugs. However, the agency would consider products employing the same transgenes but vectors from the same viral family on a case-by-case basis. In its evaluation, the agency would also consider additional features, such as gene regulatory elements and the type of cell(s) modified, to determine a product’s eligibility for orphan drug status and market exclusivity. The agency believes that by providing a consistent roadmap for the development of gene and cell therapies, such guidelines will spur innovation and greater competition.