The FDA has predicted that by 2025 there will be 10-20 new drug approvals a year in cell and gene therapy, detailing their strategy to keep up.
Over 800 cell and gene therapy drugs are currently in the FDA pipeline, with around 200 additional Investigation New Drug (IND) applications per year. The agency has singled the field out for attention to advance it.
The increasing activity reflects the rise seen at the turning point in the popularity of antibodies in the mid-1990s. Here, the critical development for the turning point has been safe and effective vectors for gene therapy delivery. Adeno-associated virus (AAV) vectors are a good example.
The increase is expected based on the technological advancement in vectors and the clinical promise of the new innovations.
The diversification of cell and gene therapy is unlike anything seen with antibodies or other treatments. The products are very easily adjusted to fit other ailments. This increases the number of new drugs being planned.
With this workload close on the horizon, there could not be a worse time for the US government shutdown, majorly decreasing the FDA's capacity. The backlog from the shutdown will make the task of keeping up with these new therapies even tougher.
The FDA’s method for tackling this emerging field is a four-pronged approach.
- Accelerated approval pathways
- Increasing staff
- New guidance documents for the field
- Taking action on non-compliance
- Expediting the process
Many accelerated approval pathways exist within the FDA and many types of cell and gene therapy would be suitable. The programme for regenerative medicine advanced therapy (RMAT) is one such pathway that could be taken advantage of. The drugs that cure as opposed to treat diseases have been particularly identified for this expedited pathway due to their effectiveness.
The FDA has said it will work with sponsors to make the maximum use of these schemes. However, the reduced pre-market trials may not be sufficient for cell and gene therapies.
The nature of the drug is that there are rare instances of off-target effects. The rarity of side effects means the size of the pre-market trials may not be sufficient to identify them.
Additionally, many cell and gene therapies are for rare diseases, so finding enough appropriate candidates is not always possible.
Fortunately, the other advantage of the expedited pathway is the postmarket follow-up studies. These studies increase the dataset size to identify any such rare side effects.
- Increasing clinical review staff
INDs need reviewing by staff to advance their application. To keep up with the increased submissions, the FDA aims to bring on board about 50 additional clinical reviewers. These new additions will oversee the clinical investigation, development and review of new products.
- Specialised guidance
The FDA plans to write more specialised guidance on the subject of gene therapy product development. The guidance documents will focus on the specific alterations to accelerated approval designation, the accelerated approval process itself and the areas of product development.
- Improve application efficiency to stop non-compliance
According to the FDA, there are a number of individuals working on products that are subject to pre-market approval but they are not complying. The distribution of these non-compliant products poses potentially significant safety concerns to patients. The FDA has reached out to these companies but has been unable to start a dialogue.
Increasing enforcement action on these non-complying companies will be beneficial to the field. Additionally, the FDA has another approach to resolve the issue. The agency will develop more efficient entry pathways for new sponsors to come into regulatory compliance and gain approval of their Biologics Licence Application (BLA).
One improvement to the pathway for BLAs is a new proposed trial design. Individual researchers could pool their clinical data after following a common manufacturing protocol, and therefore develop a more robust data set and helping smaller sponsors to achieve sufficiently sized clinical trials. This is already in active discussion in the FDA.
Collaboration is becoming a big part of the cell and gene therapy industry. This FDA strategy of pooling research will be in line with this, the agency said.
A final caution
The FDA has acknowledged the huge promise of these therapies. However, fear of the unknown gives the agency caution.
“Our efforts are aimed at helping innovators proactively address these potential risks, while we outline a modern and efficient pathway for the continued development of these innovations,” the FDA explained in a statement.
Considering the reduced burn rate of limited funds that the FDA is functioning on, these expensive new steps have been announced at a seemingly odd time. An FDA spokeswoman told The Pink Sheet that the agency does not have an update on a specific timeline at this time.