More on Geron Leaving the Embryonic Stem Cell Business

According to the Washington Post, “Geron Corp., a pioneer in stem cell research that has been testing a spinal cord injury treatment, said late Monday that it’s halting development of its stem cell programs to conserve funds. It is seeking partners to take on the programs’ assets and is laying off much of its staff…In a statement, the company said the decision to narrow its focus “was made after a strategic review of the costs, … timelines and clinical, manufacturing and regulatory complexities associated with the company’s research and clinical-stage assets.”

Bio-ethicist Wesley Smith sees something potentially nefarious at work. Geron was in the midst of a Phase I clinical trial for its embryonic stem cell-derived oligodendrocyte precursor cell line GRNOPC1. Embryonic stem cells (ESCs) are made from human blastocyst-stage embryos. The derivation of ESC lines requires the dis-assembly, and consequent death of the embryo, which is a human person in the very early stages of development. The GRNOPC1 cell line was made from ESC line H1, which was originally made in the laboratory of James Thomson at the University of Wisconsin when he made the first human ESC lines. H1 was originally called WA01.

The cell line GRNOPC1 was made by differentiating H1 cells into oligodendrocyte progenitor cells (OPCs). OPCs are stem cells found in the central nervous system. They divide to form oligodendrocytes, which wrap around the axons of neurons and help them conduct their nerve impulses much faster than they normally would. Because oligodendrocytes take a beating during spinal cord injury, replacing them can potentially help spinal cord injury patients recover some function. Transplanted GRNOPC1 cells have been shown to improve the function of mice that have suffered spinal cord injuries. Geron has also done quite of bit of work to establish that GRNOPC1 cells are safe, at least in mice.

According the Geron’s web site, Geron worked with collaborators at various universities to demonstrate that GRNOPC1 improved movement in spinal cord-injured animals if they were implanted seven days after the spinal cord injury. When Geron scientists examined the spinal cords of the animals that had received the GRNOPC1 cells, they found that the transplanted OPCs had engrafted or became a part of the spinal cord and were functioning as expected. They published these data in May 2005 in the Journal of Neuroscience. Geron and it collaborators also implanted GRNOPC1 cells into spinal cord injured animals nine months after injury. Tissue examinations of these laboratory animals showed that the site of spinal cord injury was filled with GRNOPC1 cells and properly myelinated rat axons that were crossing the lesion. This is something that axons do not do after spinal cord injury, because the inflammation in the spinal cord kills all neurons in the area and axons that traverse the damaged area. Neurons may not be anywhere near the area of spinal cord damage, but if their axons (the portion of the neuron that directs nerve impulses away from the cell body of the neuron) extend through the area, the axons are severed and the neuron retracts its axons. The target that was receiving nerve inputs from the axon now lacks any input from the nervous system and if that target is a skeletal muscle, which is the target for motor neurons, the muscle becomes incapable of contracting.

Geron also notes on its website that all preclinical studies performed in animals provided the rationale for the use of GRNOPC1 in treating spinal injuries in human clinical trials. Extensive safety testing also satisfied the Food and Drug Administration that they were safe for use in humans. The FDA, therefore, gave Geron the green light to test their GRNOPC1 cell line in human patients who had recently suffered spinal cord injuries.

However, Geron is now leaving the very field it pioneered. This is being reported as a calculated business move that is due to the gargantuan financial investment required to bring embryonic stem cells into the world of everyday medicine. Late Monday this week (November 14, 2011), the company said it would cease all studies of stem cell-based treatments for spinal cord injury. This treatment was the first ever embryonic stem cell trial approved in the U.S. Geron, a Menlo Park, California, company has long been viewed as the undisputed leader in stem cell therapies. This leadership role is due to patents Geron holds on technology used to grow, manipulate and inject stem cells into the human body. In fact, Geron helped finance researchers at the University of Wisconsin who first isolated human embryonic stem cells in 1998, allowing the cells to be grown in the laboratory.

Wesley Smith smells a potential rat. He asks the following questions: “That being so, Geron and the media have an obligation to explain the why of this story in some detail and without spin. Was it the recent European ruling banning the patenting of embryonic stem cell products (about which I wrote) a factor? Was its human trial a disappointment? If it is out of money, why aren’t venture capitalists more willing to invest more in the field if it is so promising? I am sure you all have questions of your own.” These are all good questions, but it is entirely possible that Geron, having already sunk 25 million dollars into this venture and seeing that their product was still decades away from coming to the market, they decided to cut their losses and sell it to someone else. Geron has some anti-cancer drugs in the clinical trial pipeline that are doing very well in their clinical trials. These will probably be ready for production long before the stem cell lines are ever ready. Therefore, the financial motive is probably factor. Geron CEO said as much in his statement: “CEO Dr. John Scarlett told investors and analysts Tuesday that focusing on cancer drugs will allow Geron to make more money in a shorter period of time, particularly when “big pharma and big biotech companies are increasingly hungry for first-in-class cancer programs.”

With respect to the poor clinical trials, Geron press releases have revealed no such thing to date. I get Geron’s press releases, and while these are written from a source within the company that has a vested interest in making the news sound good, the phase I trials, for all intents and purposes, seemed to be going well. GRNOPC1 cells were well tolerated, and the Phase I test was meant to only test safety and not efficacy. If there were no improvements in the human patients, it seems premature to suspect that the company bailed on the basis on this one test with four patients. To suspect that the human subject experienced terrible side effects is to accuse Geron of lying, which is improper without better evidence.

Nevertheless, this is a significant story, in that ESCs do not seem to be able to compete with their adult and fetal counterparts at this time. The continued successes of cord blood, bone marrow, and other stem cell treatments are making it harder and harder for ESCs to find a niche in the market. Even in the case of spinal cord injuries, adult stem cells have made progress in helping quadriplegic patients walk with braces. Such news does not make it into the papers as often as it should, but people need to know that killing young human beings is not the most morally acceptable way to make the regenerative cures that we want.

Another factor in Geron’s decision has to be the recent decision of the European Union’s highest court that ESCs and products derived from ESCs are not patentable under applicable EU law. Because Geron probably viewed Europe as potential market for their products, this would have been a huge blow to their future marketing plans. Geron will continue to make innovative medicines, but ESC-derived products, for now, will not be one of them.