CIRM-funded stem cell clinical trial for spinal cord injury expands patient recruitment

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It’s always great to start the week off with some good news. Today we learned that the Food and Drug Administration (FDA) has given Asterias Biotherapeutics approval to expand the number and type of people with spinal cord injuries that it treats in their CIRM-funded clinical trial.

Up till now, Asterias has been treating people who have injuries at the C5-C7 level, those are the lowest levels of the cervical spine, near the base of the neck. Now they will be able to treat people with injuries at the C4 level, that’s not only higher up the neck but it’s also the second most common form of spinal cord injury.

In a news release Dr. Ed Wirth, Asterias’ Chief Medical Officer, says this is a vote of confidence from the FDA in the company’s AST-OPC1 stem cell therapy:

“FDA’s decision to allow the company to enroll qualified patients with C-4 level injuries is the result of the data supporting the safety of both AST-OPC1 and the procedure to inject the cells and means that the second most common cervical spinal cord injury population can now be eligible to receive AST-OPC1. The overall changes to the study protocol will enhance our ability to enroll qualified patient candidates for our current SCiStar study and we also expect the changes to help enrollment rates in a future, larger clinical study.”

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Photo courtesy Shepherd Center, Atlanta

People who are injured at the C4 level are typically paralyzed from the neck down and need constant help, while people with C5-C7 injuries typically have some use of their hands and arms. Caring for someone with a C4 injury is expensive, with lifetime costs estimated around $5 million. Anything that could help people recover some movement would not only reduce those costs but would, more importantly, also increase the quality of life for people.

Asterias is not only expanding the patient population they are working with, they are also expanding the window for treating the injury. Currently patients have to be enrolled from 14 to 30 days post injury. In this new C4 group that window has been extended to 21 to 42 days post injury.

The reason for that change is that because C4 is higher up in the neck, newly injured people often need to be placed on a ventilator to help stabilize them. These patients take a little more time to recover from the initial trauma before they are ready to be treated.

We have blogged several times (here, here and here) about the encouraging news from the Asterias trial and how it appears to be helping people with injuries at the C5-C7 level recover some movement in their arms and hands. In some cases, such as with Kris Boesen for example, the improvement has been quite dramatic. Now the hope is that this new patient population will see similar benefits.

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Kris Boesen, CIRM spinal cord injury clinical trial patient.

The study is being conducted at six centers in the U.S., including some here in California,  and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment.

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Good news from Asterias’ CIRM-funded spinal cord injury trial

This week in the stem cell field, all eyes are on Asterias Biotherapeutics, a California-based company that’s testing a stem cell based-therapy in a CIRM-funded clinical trial for spinal cord injury patients. The company launched its Phase 1/2a clinical trial back in 2014 with the goal of determining the safety of the therapy and the optimal dose of AST-OPC1 cells to transplant into patients.

astopc1AST-OPC1 cells are oligodendrocyte progenitor cells derived from embryonic stem cells. These are cells located in the brain and spinal cord that develop into support cells that help nerve cells function and communicate with each other.

Asterias is transplanting AST-OPC1 cells into patients that have recently suffered from severe spinal cord injuries in their neck. This type of injury leaves patients paralyzed without any feeling from their neck down. By transplanting cells that can help the nerve cells at the injury site reform their connections, Asterias hopes that their treatment will allow patients to regain some form of movement and feeling.

And it seems that their hope is turning into reality. Yesterday, Asterias reported in a news release that five patients who received a dose of 10 million cells showed improvements in their ability to move after six months after their treatment. All five patients improved one level on the motor function scale, while one patient improved by two levels. A total of six patients received the 10 million cell dose, but so far only five of them have completed the six-month follow-up study, three of which have completed the nine-month follow-up study.

We’ve profiled two of these six patients previously on the Stem Cellar. Kris Boesen was the first patient treated with 10 million cells and has experienced the most improvement. He has regained the use of his hands and arms and can now feed himself and lift weights. Local high school student, Jake Javier, was the fifth patient in this part of the trial, and you can read about his story here.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

Kris Boesen, CIRM spinal cord injury clinical trial patient.

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Jake Javier and his Mom

The lead investigator on this trial, Dr. Richard Fessler, explained the remarkable progress that these patients have made since their treatment:

“With these patients, we are seeing what we believe are meaningful improvements in their ability to use their arms, hands and fingers at six months and nine months following AST-OPC1 administration. Recovery of upper extremity motor function is critically important to patients with complete cervical spinal cord injuries, since this can dramatically improve quality of life and their ability to live independently.”

Asterias will continue to monitor these patients for changes or improvements in movement and will give an update when these patients have passed the 12-month mark since their transplant. However, these encouraging preliminary results have prompted the company to look ahead towards advancing their treatment down the regulatory approval pathway, out of clinical trials and into patients.

Asterias CEO, Steve Cartt, commented,

Steve Cartt, CEO of Asterias Biotherapeutics

Steve Cartt, CEO of Asterias Biotherapeutics

“These results to date are quite encouraging, and we look forward to initiating discussions with the FDA in mid-2017 to begin to determine the most appropriate clinical and regulatory path forward for this innovative therapy.”

 

Talking with the US FDA will likely mean that Asterias will need to show further proof that their stem cell-based therapy actually improves movement in patients, rather than the patients spontaneously regaining movement (which has been observed in patients before). FierceBiotech made this point in a piece they published yesterday on this trial.

“Those discussions with FDA could lead to a more rigorous examination of the effect of AST-OPC1. Some patients with spinal injury experience spontaneous recovery. Asterias has put together matched historical data it claims show “a meaningful difference in the motor function recovery seen to date in patients treated with the 10 million cell dose of AST-OPC1.” But the jury will remain out until Asterias pushes ahead with plans to run a randomized controlled trial.”

In the meantime, Asterias is testing a higher dose of 20 million AST-OPC1 cells in a separate group of spinal cord injury patients. They believe this number is the optimal dose of cells for achieving the highest motor improvement in patients.

2017 will bring more results and hopefully more good news about Asterias’ clinical trial for spinal cord injury. And as always, we’ll keep you informed with any updates on our Stem Cellar Blog.

First spinal cord injury trial patient gets maximum stem cell dose

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Kris Boesen, CIRM spinal cord injury clinical trial patient.

There comes a pivotal point in every experiment where you say “ok, now we are going to see if this really works.” We may be at that point in the clinical trial we are funding to see if stem cells can help people with spinal cord injuries.

Today Asterias Biotherapeutics announced they have given the first patient in the clinical trial the highest dose of 20 million cells. The therapy was administered at Santa Clara Valley Medical Center (SCVMC) in San Jose, California where Jake Javier – a young man who was treated at an earlier stage of the trial – was treated. You can read Jake’s story here.

The goal of the trial is to test the safety of transplanting three escalating doses of AST-OPC1 cells. These are a form of cell called oligodendrocyte progenitors, which are capable of becoming several different kinds of nerve cells, some of which play a supporting role and help protect nerve cells in the central nervous system – the area damaged in spinal cord injury.

In a news release, Dr. Edward Wirth, Asterias’ Chief Medical Officer, says this could be a crucial phase in the trial:

“We have been very encouraged by the early clinical efficacy and safety data for AST-OPC1, and we now look forward to evaluating the 20 million cell dose in complete cervical spinal cord injury patients. Based on extensive pre-clinical research, this is in the dosing range where we would expect to see optimal clinical improvement in these patients.”

To be eligible, individuals have to have experienced a severe neck injury in the last 30 days, one that has left them with no sensation or movement below the level of their injury, and that means they have typically lost all lower limb function and most hand and arm function.

In the first phase individuals were given 2 million cells. This was primarily to make sure that this approach was safe and wouldn’t cause any problems for the patients. The second phase boosted that dose to ten million cells. That was thought to be about half the therapeutic dose but it seemed to help all those enrolled. By 90 days after the transplant all five patients treated with ten million cells had shown some level of recovery of at least one motor level, meaning they had regained some use of their arms and/or hands on at least one side of their body. Two of the patients experienced an improvement of two motor levels. Perhaps the most impressive was Kris Boesen, who regained movement and strength in both his arms and hands. He says he is even experiencing some movement in his legs.

All this is, of course, tremendously encouraging, but we also have to sound a note of caution. Sometimes individuals experience spontaneous recovery after an accident like this. The fact that all five patients in the 10 million cell group did well suggests that this may be more than just a coincidence. That’s why this next group, the 20 million cell cohort, is so important.

As Steve McKenna, Chief of the Trauma Center at SCVMC, says; if we are truly going to see an improvement in people’s condition because of the stem cell transplant, this is when we would expect to see it:

“The early efficacy results presented in September from the 10 million cell AIS-A cohort were quite encouraging, and we’re looking forward to seeing if those meaningful functional improvements are maintained through six months and beyond. We are also looking forward to seeing the results in patients from the higher 20 million cell AST-OPC1 dose, as well as results in the first AIS-B patients.”

For more information about the Asterias clinical trial, including locations and eligibility requirements, go here: www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

We can never talk about this clinical trial without paying tribute to a tremendous patient advocate and a great champion of stem cell research, Roman Reed. He’s the driving force behind the Roman Reed Spinal Cord Injury Research Act  which helped fund the pioneering research of Dr. Hans Keirstead that laid the groundwork for this clinical trial.