Q&A about Geron's decision and its implications for the stem cell field

Yesterday Geron announced that they would be discontinuing their embryonic stem cell program, including the groundbreaking spinal cord injury trial that CIRM had been supporting. You can read more about the decision in Geron's announcement and in CIRM's press release. Geron has returned the $6.4 million they had received from CIRM with accrued interest.

It's not uncommon for companies to discontinue research programs for financial reasons. What makes this announcement different is the high-profile nature of the company and the trial. Geron was the first to pave a path through the Food and Drug Administration (FDA) to test a human embryonic stem cell-derived product in clinical trials. The trial was seen as a sign of hope for people waiting for therapies derived from embryonic stem cells, so its termination came as a shock to many patients and their families.

Today we wanted to take a step back and look at the announcement and what it means.

Q. What was Geron testing in their spinal cord injury trial?
A. Geron started with human embryonic stem cells and matured them into the precursor of type of cell that forms the coating on neurons. That coating is lost soon after a spinal cord injury, and without the coating electrical signals can't travel up and down the spine. The idea was that after injecting some of these precursor cells they would mature and form a new coating on the spinal cord neurons, restoring the ability of signals to cross the injury site.

This first trial was in its early stages and was testing a low dose of the cells to make sure they are safe. Remember that when this trial began the cells had only been tested in animals. Only after the company showed that the cells were safe would they be able to inject a dose that was expected to be high enough to show some signs of success.

Q. Why did Geron decide to discontinue the stem cell program?
A. The company decided to focus its resources on two oncology drugs that are in clinical trials. The decision was made based on financial considerations, not based on concerns about the science. Such a move is relatively common for biotechnology companies especially during the complex early-phase clinical trials such as this one.

Q. What does Geron’s decision mean for the field of stem cell research?
A. The field of stem cell research continues to be strong, with many promising therapies in the pipeline. Geron leaving the field does not alter the existing excellent programs that are working toward and carrying out clinical trials.


Q. What will happen to the patients who already received the cells?
A. Geron has been closely following the patients who have received the cells. So far, the patients have tolerated their injections and haven't shown any serious adverse effects from the cells. The company says it will continue monitoring those patients and keeping the FDA appraised of the results.


Q. Will the trial continue?
A. For now, the trial is discontinued. Geron says they are looking for partners to further develop their stem cell programs. Whether or not the trial continues depends on whether partners come forward with the resources and the interest in continuing it.


Q. What happened to CIRM's money?
A. CIRM had committed $24.8 million to support the trial, of which $6.4 had been dispersed. Geron has already returned the money in its entirety with accrued interest.


Q. Are there other trials testing products made from embryonic stem cells?
A. Yes. The company Advanced Cell Technology is testing an embryonic stem cell-derived product in two forms of blindness: macular degeneration and Stargardt's disease. They have already begun enrolling patients in those trials.

Q. What other trials are in the pipeline to test embryonic stem cells?
A. World-wide, many groups are moving closer to clinical trials testing cells derived from embryonic stem cells. CIRM has funded four disease teams that have the goal of submitting a request to the FDA to move forward with clinical trials (that request is also known as an Investigational New Drug or IND filing). Those disease teams are working on diabetes, stroke, macular degeneration and ALS (also known as Lou Gehrig's disease).

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Forming industry partnerships, ensuring new therapies reach patients

At our governing board meeting on October 26, the board approved a $30 million initiative that will be critical for making sure that research funded by CIRM eventually makes it to patients.

In the past year, CIRM has begun funding early phase clinical trials for stem cell-based therapies. These early phase clinical trials are done to make sure that the prospective therapy is safe, and can also show preliminary evidence that it may be effective. What we don't fund are the large, later phase clinical trials that the Food and Drug Administration requires to confirm whether or not the therapy is safe and effective before approving a new therapy for patients. (This resource has information about the stages of therapy development.)

These large clinical trials cost a lot of money, and conducting these trials can benefit from the kinds of expertise that industry partners can provide.

Ideally, what would happen is that CIRM would fund the research leading up to FDA approval to begin a clinical trial, and we'll fund some early phase trials (or provide matching funds through a loan, such as the Geron trial we're supporting now). For trials that start with investigators in universities, or in small companies, larger industry partners would then have the opportunity to help fund the early trials and would pick up any project that succeeded in early trials and carry out the expensive later-stage confirmatory trials.

The new $30 million Strategic Partnership Funding Program will promote the partnerships between academic groups or small businesses and the larger industry partners whose participation will be critical for carrying out the late-stage clinical trials. Forming those relationships also provides our grantees with a source of advice that can help them design their early trials and overcome regulatory hurdles.

Elona Baum, CIRM General Counsel and Vice President of Business Development, led the effort to develop this fund. She said:

“With this fund we want to make sure that CIRM grantees get early access to the expertise of biopharmaceutical companies who will then, at Phase III, bring the project through the goal line. We want to increase the likelihood that CIRM research has access to funding in the later stage of development which is critical to ensuring it gets into the market place and helps patients in need. We're being proactive by engaging industry early in the process of developing new therapies.”

This Partnership fund is one portion of an overall Opportunity Fund. The two other parts of that fund will be presented to the board for approval in December or January. Together, the funds are designed to keep CIRM nimble and looking ahead to the resources and expertise our grantees will need in the future if our funding is going to be a success.

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First patient enrolls in a clinical trial funded by CIRM

Today is a landmark day for CIRM: We announced that the first patient had been enrolled in a clinical trial based on stem cell agency funding. You can read our press release here.

The patient was part of Menlo Park-based Geron's phase I trial for spinal cord injury, which was awarded $25 million from CIRM in May. Stanford neurosurgeon Gary Steinberg, MD, PhD, implanted the cells Sept. 17 at Rehabilitation Trauma Center at Santa Clara Valley Medical Center.

Stanford had this to say about the trial:

Researchers at Geron collaborated with Hans Keirstead, PhD, and his laboratory team at UC-Irvine to develop a way to coax human embryonic stem cells to become a mixture of cells that include oligodendrocyte precursors. Oligodendrocytes are cells in the brain and the central nervous system that wrap nerve cells with an insulating material called myelin. This myelin sheath is necessary for the transmission of the electric signals along the spinal cord that trigger muscles to move, and relay our sense of touch and temperature. Damage to this sheath caused by trauma is a common cause of paralysis.

To be eligible for the trial, patients must have recent (within 14 days of injury) non-penetrating damage to a specific region of their thoracic spine — an area roughly from the top of the shoulder blades to the bottom of the rib cage. The damage must cause complete paraplegia, meaning that they have normal sensation or movement to the level of the hands, but not from the trunk to the toes.

During the procedure, Steinberg applied about 2 million of the special cells, called GRNOPC1, directly into the injured area of the patient’s spinal cord.

“We are quite pleased that the surgery was completed successfully and the patient is doing well,” said Steinberg.

When the CIRM governing board voted to fund the Geron trial, spinal cord injury advocate Roman Reed wrote a guest blog entry in which he said:

In a truly historic partnership for stem cell research and cure, state funding from what has been called “Roman's Law” gave Hans Keirstead the seed money to achieve empirical evidence and proof of principle. Hans then sold his pioneering technique to Geron, and advanced biotechnology farther by founding California Stem Cell with the proceeds.

With admirable courage and determination, Geron pushed this science all the way to FDA approval to become the world's first embryonic stem cell derived human clinical trial.

Now our beloved state agency, the California Institute for Regenerative Medicine will provide funding to bring about a full and complete Human Clinical Trial!!

The Keirstead/Geron/CIRM Trials advances the entire field of stem cell research.

Today's announcement marks a milestone that is a critical step toward making safe and effective stem cell-based therapies available to patients.

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Guest blogger Roman Reed: spinal cord injury stem cell trials get $25 million boost from CIRM

From the editor: Yesterday the CIRM governing board approved a $25 million loan to help fund a trial testing the use of an embryonic stem cell-derived therapy for spinal cord injury. Here's our press release. Our guest blogger Roman Reed was injured in a football accident and has since fought tirelessly for spinal cord injury research.

Yesterday's announcement that CIRM will help fund the Geron spinal cord injury Human Trials ensures that paralysis cure will have it's day!

It was my honor to be the inspiration of the Roman Reed Spinal Cord Injury Research Act in 1999, which provided the original funding for Hans Keirstead's research which is being tested in these trials, the first in the world.

However, the expense of the trials might conceivably have exhausted Geron's financial resources, narrowing the scope of the trials. This would have been devastating, not only to our hopes for paralysis cure but also for the entire field. The world is watching. Had the trials been too limited for lack of funding, it might have cast a shadow of doubt on its outcome-- instead, the trials go forward, strongly.

Geron's nine year struggle to build a mountain of preliminary data (so the FDA could approve the human trials) was an heroic effort, on which so much depended. With the leadership of Geron, the courageous biomed company came through for California and our country, and the world-- and so did the California stem cell program.

When the oversight committee announced its decision yesterday, it authorized a $25 million dollar loan to Geron to assist in the clinical trials. This was a careful loan, milestone driven, with each installment given only on the successful completion of predetermined goals.

I join the patient advocate community across the globe in expressing absolute full support of CIRM's descision to provide funding for America's first hESC derived Human Clinical Trials.

As a Patient and Patient advocate, I am overjoyed that Prop.71 took a stand for the Geron trials, the most important experiment in the world for the fields of spinal cord injury, neuro-regenerative medicine and stem cell research.

Truly, the Geron Trials are setting the pace of spinal cord injury. Paralysis affects 650,000 Californians and 1.9 million Americans, with an additional 5.6 million Americans who suffer from all forms of paralysis. (Here's information about CIRM's funding for spinal cord injury stem cell research.)

This epic step was accomplished through partnership and collaboration through a new age continum of support beginning with State funding from Roman Reed Spinal Cord Injury Research Act, Education at the University of California, Irvine, private industry support from Geron and voter-approved CIRM/State funds.

In a truly historic partnership for stem cell research and cure, state funding from what has been called “Roman's Law” gave Hans Keirstead the seed money to achieve empirical evidence and proof of principle. Hans then sold his pioneering technique to Geron, and advanced biotechnology farther by founding California Stem Cell with the proceeds.

With admirable courage and determination, Geron pushed this science all the way to FDA approval to become the world's first embryonic stem cell derived human clinical trial.

Now our beloved state agency, the California Institute for Regenerative Medicine will provide funding to bring about a full and complete Human Clinical Trial!!

The Keirstead/Geron/CIRM Trials advances the entire field of stem cell research.

Today's vote of support is a truly historic milestone in medicine.

Ladies and Gentlemen welcome to the beginning of personalized stem cell medicine and cure!

Thank you Prop.71 for Taking A Stand-- So One Day-Everybody Can!

Here's Roman Reed discussing stem cell-based therapies for spinal cord injury:

First patient from Geron spinal cord injury trial speaks up

A story by Rob Stein at the Washington Post is reporting that the first patient to participate in Geron's groundbreaking embryonic stem cell-based trial for spinal cord injury has come forward.

This is both exciting news and no news. It's exciting because scientists and people living with spinal cord injury and their families are all watching this trial closely. Any news is of interest. However, at this point it's too soon to know if the cells have been effective.

For those who haven't been following this story, Geron is conducting a trial in which they inject primitive neural cells derived from embryonic stem cells into the region surrounding a recent spinal cord injury. In work with rodents conducted by CIRM grantee Hans Keirstead at the University of California, Irvine, the cells were able to restore movement to the hind limbs after an injury. (As an aside, that earliest work was conducted through funds from the Roman Reed Spinal Cord Injury Research Act, which is currently being debated by the state.)

The first patient was Timothy J. Atchison of Chatom, Ala. According to the Washington Post:

Atchison, known as T.J. to his family and friends, was a student at the University of South Alabama College of Nursing when his car crashed on Sept. 25, which, Atchison noted, was the birthday of Christopher Reeve, the actor who suffered a devastating spinal cord injury.

After undergoing emergency treatment at a regional medical center, Atchison was transferred to the Shepherd Center in Atlanta, which specializes in spinal cord injuries, for rehabilitation. It was there that he agreed to let doctors inject him with the drug — more than 2 million cells made from stem cells into his spine, he said.

Like all initial trials in the U.S., this one is primarily testing whether the cells are safe, but of course it is also being closely watched for signs that the cells were effective (read more from the NIH about phases of a clinical trial). It's too soon for scientists to know whether the injected cells are able to help repair damage after spinal cord injury such as the one Atchison suffered after his car crashed.

Geron intends to test the cells on 10 people at seven sites around the country, of which Stanford University recently announced it was one. The Washington Post describes the procedure:

Surgeons planned to use specially designed equipment to infuse into the first patient’s spine about 2 million “oligodendrocyte progenitor” cells, which Geron scientists had created in the laboratory from embryonic stem cells obtained from days-old embryos left over from fertility treatments. The hope is that the cells will form a restorative sheath around the damaged spinal cord. In tests in hundreds of rats, partially paralyzed animals regained the ability to move, according to Geron.

The Geron trial isn't the only approach to using stem cells to treat spinal cord injury, though it is the first to clinical trial. Here's a list of CIRM grantees working on other approaches, including some using adult, embryonic or reprogrammed iPS cells.

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A second stem cell trial for spinal cord injury

We've posted quite a bit about the Geron trial testing an embryonic stem cell-derived therapy for spinal cord injury. Now Palo Alto-based StemCells Inc has started a trial in Switzerland testing a tissue-specific stem cell therapy. The company announced that they'll be enrolling 12 people who have no feeling below their injury in this initial safety trial. Unlike the Geron trial, which is specifically enrolling people with recent injuries, StemCells Inc is testing their product in people whose injuries are three to twelve months old.

A significant difference between these two trials is the type of cell being tested. (You can read more about different types of stem cells in our Stem Cell Basics.) The Geron trial uses embryonic stem cells that have been grown in large quantities then matured into a type of neuronal precursor cells. In rodents, those cells are able to restore function after a recent spinal cord injury. The Geron trials will show whether those cells are also effective in people.

By contrast, the StemCells Inc trial uses cells that are already committed to becoming a type of neuronal cell. These neuronal stem cells can repair spinal cord injuries in rodents. Like the Geron trial, StemCells Inc is first testing these cells in a small number of people to ensure that they are safe.

It's exciting to see several different approaches being tested. When I think about these early stem cell trials I often reflect on the earliest cancer trials. I don't know very much about the first chemotherapy for lymphoma, but I'm grateful to the scientists who kept trying new approaches and improving on early successes because they're the reason my mother has been cancer-free for the past 10 years.

Whether or not these first trials are successful (and honestly, more early trials fail than succeed) we are witnessing the start of what I hope will one day be a cure for all those people living with spinal cord injuries. That cure might involve embryonic stem cells, neuronal stem cells, drugs tested on stem cells in the lab, or a combination of those approaches depending on the type of injury. CIRM is funding all of those stem cell approaches in the hopes finding the quickest path to a cure.

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Geron trial -- baby steps toward a cure

Today Geron announced that the first patient had been treated in their groundbreaking trial based on human embryonic stem cells.

At first blush: Woo hoo!! This is the first test of technology that holds hope for millions of people living with spinal cord injury and other diseases.

But it’s important to remember that this first trial is a very, very early step. Any potential therapy goes through three rounds of human trials. The first, phase I, trial is intended only to verify that the potential therapy is safe. This trial can establish dosing and begin to monitor side effects of the drug or treatment. In some cases a phase I trial will also begin to reveal whether the drug or therapy has signs of effectiveness, but that’s not the primary role of the trial.

After the small phase I trial comes a slightly larger phase II trial. It confirms safety and also begins to look directly at whether the drug or therapy is effective.

It isn’t until some years later that a large phase III trial confirms whether the drug or therapy is effective compared to standard therapy.

Many potential therapies fail after the phase I trial, even after years of positive results in animals. Humans aren’t mice (or other laboratory animals) and scientists can’t ever know what side effects will turn up in their human patients.

That’s why it is important to temper that initial “woo hoo” with a bit of patience. This could be one of those trials that fails phase I. Or phase II. Or phase III. But as many years of biomedical research have shown, for every failed trial there are also a number of successful trials. Whatever the results of this first phase I trial, it’s the beginning of a new era that will one day result in the first successful therapy based on human embryonic stem cells. That day will have scientists and patients alike whooping for joy.

Here's patient advocate Roman Reed talking about what a stem cell therapy for spinal cord injury means to him:

Geron to begin stem cell trial for spinal cord injury

Hans Keirstead, UC Irvine

The FDA has lifted a clinical hold that has been in place since 2008 on Menlo Park, CA-based Geron's proposed trial for spinal cord injury. The multi-center phase I trial will be the world's first trial of a therapy based on embryonic stem cells.

In a press release, the company's president and CEO, Thomas Okarma, said:

"Our goals for the application of GRNOPC1 in subacute spinal cord injury are unchanged - to achieve restoration of spinal cord function by the injection of hESC-derived oligodendrocyte progenitor cells directly into the lesion site of the patient's injured spinal cord."

Alan Trouson, CIRM President, said:

“This is an important milestone for the whole field to have an embryonic stem cell therapeutic in clinical trials. We are looking with hope and expectation that the transplant will be safe and effective.”

The trial is based on work by CIRM grantee Hans Keirstead at UC Irvine. Prior to CIRM funding, his team matured embryonic stem cells into a form of neuronal cell called oligodendrocytes. When injected into rats with spinal cord injury, those cells protected the remaining spinal cord neurons and allowed the rats to walk.

In their press release, Geron described the reasons for the clinical hold:

The clinical hold was placed following results from a single preclinical animal study in which Geron observed a higher frequency of small cysts within the injury site in the spinal cord of animals injected with GRNOPC1 than had previously been noted in numerous foregoing studies.

In follow up work, Geron was able to prove to the FDA the safety of their stem cell product. The work directly leading to this clinical trial took place prior to the passage of proposition 71 to create CIRM. CIRM has funded follow-up work by Keirstead and others to improve on this potential therapy and expand the application of these cells to other diseases.

Here is Hans Keirstead discussing the long path from basic research to this clinical trial:





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