- The Food and Drug Administration on Tuesday finalized a slate of policies for the development and assessment of gene therapies, clarifying its views as it prepares for a coming surge of new treatments in diseases like hemophilia and muscular dystrophy.
- By 2025, the FDA expects it will be reviewing and approving between 10 and 20 cell and gene therapies each year. Guidance documents like the seven issued Tuesday give drugmakers a clearer sense of how the agency will respond.
- Unlike traditional small molecule drugs or biologics, gene therapies are designed to be one-time fixes for inherited genetic defects, raising critical questions about how companies should measure the durability of a treatment's benefit. The FDA acknowledged this uncertainty in its documents, emphasizing the need for long-term follow-up to complement the information drugmakers provide via pre-market testing.
FDA approvals for Roche's blindness therapy and Novartis' muscular atrophy treatment were landmark moments for the gene therapy field, showing what's possible through gene-based medicine.
The next several years look set to feature many more milestones, with nearly 1,000 gene therapy studies currently underway and some half dozen treatments advancing quickly toward regulatory review.
"These therapies, once only conceptual, are rapidly becoming a therapeutic reality," FDA Commissioner Stephen Hahn, who was sworn in as agency chief last month, said in a statement.
The guidance documents published Tuesday were expected, as the agency had previously issued draft versions of six and signaled last July that finalized forms would be forthcoming.
In addition, regulators issued a draft guidance on how they plan to determine whether gene therapy products qualify as orphan drugs, and whether a new product should receive the corresponding seven years of market exclusivity.
It's an important point, as the advancing wave of research will likely bring forward competing medicines that offer patients the possibility of one-and-done treatment. Should an initial therapy secure a regulatory monopoly, subsequent drugs may arrive to a much reduced market.
In its document — titled "Interpreting Sameness of Gene Therapy Products under the Orphan Drug Regulations" — the FDA said it would, when assessing two treatments, consider both the therapeutic gene and the inactivated virus used to deliver it.
A treatment relying on a different viral vector, for instance, would be considered by the FDA as a different product and eligible for orphan drug exclusivity.
Currently, two types of viral vectors are commonly used as the vehicle for delivering a gene therapy to its target cells: lentiviruses and adeno-associated viruses. Different serotypes exist of each. Thirteen different AAVs, for instance, have been isolated, although some are more popular among drugmakers than others.
The FDA said it would assess differences between vectors from the same viral family on a "case-by-case" basis.
The other five guidance documents, which are largely similar to their draft versions, cover manufacturing, testing and long-term follow-up, as well as specific considerations for therapies for hemophilia, retinal disorders and rare diseases.
Long-term follow-up is a particular concern for the FDA, which wants to ensure that no safety risks crop up in gene therapy patients over time.
"The clinical review of these products frequently poses more challenging questions to regulators than reviews of more conventional drugs, such as questions about the durability of response." the FDA said in a statement.
"For some gene therapy products, therefore, although they have met the FDA's standards for approval, we may need to accept some level of uncertainty around questions of the duration of the response at the time of marketing authorization."