According to an article on CNN.com, Geron’s CEO, Dr. Tom Okarma, confirmed timelines for Geron to initiate human clinical trials with their embryonic stem (ES) cell-based treatment for spinal cord injury (SCI). He stated that the trial should start by the end of the second quarter (~June). This is really big news, as this will be the first-in-man studies using ES cells in a regulated clinical trial. Dr. Okarma made sure to mention the ‘high bar’ related to safety that the FDA has placed on this unprecedented therapeutic cell product. However, Geron has assured investors that they have worked very closely with the FDA, and Okarma’s public statements this week tells me that Geron believes that they have generated sufficient safety data to satisfy the FDA for initiating clinical testing.

You can get an idea of what this ‘high bar’ set by the FDA relates to by reading the recent press release from Advanced Cell Technologies, Inc. on the outcome to their pre-IND meeting with the FDA. That press release states that the FDA wants to see:

• studies performed under good laboratory practices (GLP)
• using cells manufactured under good manufacturing practices (GMP)
• examining several areas including
  • general safety (check all organs and systems for health- typically in immunocompromised rodents for cell products)
  • cell biodistribution (if you put the cells in the eye, where else do they go throughout the animal)
  • tumorigenicity potential of the transplanted cells
  • cell tolerability (how well does the host tissue tolerate the transplanted cells) and
  • cell survival after implantation

The press release by Advanced Cell Technologies, Inc. suggested that they had a lot more work to do before the FDA allows them to start first-in-man studies. I would imagine that Geron, in working with the FDA, has worked to set the bar extremely high for other ES cell-based products. Sometimes being first with a technology allows a company to set very high technical standards for followers to meet.

You may wonder why the safety bar is set so much higher for ES cell therapies than for many of the adult stem cell-based products that are working their way through the clinic. Bone marrow (the source for most adult stem cell-based therapies) has been used extensively in transplantation procedures for tens of years, and has a well documented safety profile with known risks. ES cell products, on the other hand, are very new technology and were initially characterized by scientists for their ability to form teratomas, or multi-tissue tumors, when transplanted into mice or rats. Teratoma formation raises all sorts of flags for the FDA, as it only takes one cell to make a tumor, so the FDA is going to want to see extensive safety profiling as it relates to biodistribution and tumorigenicity throughout the major tissues. If any of this data becomes public, or maybe it will be part of the discussion in the FDA guidance meeting in April, it will be interesting to see how long these safety studies will be required to go out. How long do you wait for a tumor to form in an animal model? For Advanced Cell, the answer to that question will likely be: “at least as long as Geron has taken their studies out.” Again, as the pioneers, Geron has the opportunity to establish industry standards.

So, 2008 is a turning point for ES cell-based therapies. This will be the year that ES cell therapies begin clinical testing in at least one product format, maybe two if Advanced Cell can execute quickly. The FDA is proactively addressing ES cell testing and is hosting an open discussion in April regarding safety issues related to these unique cell therapy products. Novocell is very much on the map, and investor JNJ should be able to provide much needed regulatory strategy advice as they watch Geron and Advanced Cell navigate the potential land mines. Importantly, ES cells are the only therapeutic cells today that have the capability of actually differentiating into tissue specific cells to regenerate organs and tissues as their main mechanism of action. However, due to the uncertain nature of the safety profile they will take longer to move through the clinic than the adult stem cell products from Osiris, Athersys, or Cytori. The unique mechanism of action of ES cells compared to their adult stem cell counterparts suggest that there could be very different outcomes in the clinical trials, and it is possible there there are some diseases and applications where only ES cells will be effective.