The FDA has scheduled an April 10, 2008 meeting to “discuss scientific considerations for safety testing for cellular therapy products derived from human embryonic stem cells.” This meeting will be followed by another meeting on April 11 that will “discuss updates on 1) research management related to the September 29, 2005 review of research programs of the Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research; 2) FDA’s Somatic Cell Therapy Letter; and 3) recently released FDA Guidance documents.” Both meetings will be open to the public, and they are allowing for 30 minutes each day for limited public presentations for those that would like to contribute and provide public input to the discussion.
This meeting has been called “unusual” in the press since “the agency typically seeks advice on whether to approve a tested drug, not how to proceed with the testing.” However, I think it is unusual in a good way. For typical molecular therapeutics (small molecules and protein-based drugs), safety testing consists of a typical panel of animal models looking at pharmacokinetics, toxicity, carcinogenicity, biodistribution, etc…, followed by Phase I human studies. There is excellent guidance and suggested standardization of this testing available (ICH being a great place to find this guidance). Cell-based therapies are significantly different than molecular therapeutics in that the cells can engraft and become part of the tissue they are treating, and they biodistribute in different ways than drugs (and can engraft other places throughout the host – this not necessarily being a bad thing). Furthermore, cell therapy doesn’t have traditional Phase I testing in healthy human subjects, so more is expected from the Phase I studies and many are combined Phase I/II studies. There are also unique safety concerns with ES cells as by definition they form teratomas (multi-tissue tumors) when transplanted into mice. Therefore, if cells engraft into the host, how long do you look for teratoma formation in your animal models? Seven days? 30 days? 6 months? 3 years? How do you monitor this in human studies? What is a reasonable way to address long term effects on other tissues outside of the disease being treated? These are the types of challenging issues being addressed (and many more), and if you are in the Rockville area in April it would be interesting to stop in and listen to the discussion.
I see this as a great proactive step that the FDA is taking. The FDA has identified an area that is critical to moving forward ES cellular therapies and they are engaging companies and their Advisory Committees for open dialogue. ES cell companies need to address the safety concerns of the therapies with a risk-based scientific approach, and having the FDA educated and engaged is a critical part of the strategy. Geron has spent of lot of time engaging the FDA in discussions, and this type of meeting will help to open the dialogue to include other ES cell-based companies that are outside of Geron’s technology or disease areas, such as Advanced Cell Technology and Novocell. The output of the meeting is often powerpoint presentations and discussion transcripts from the day, and they should be available at the FDA website. Hopefully, formal guidance will also be created to help advance these innovative therapies in a safe and responsible way.