Stem cell agency funds clinical trials in three life-threatening conditions

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A year ago the CIRM Board unanimously approved a new Strategic Plan for the stem cell agency. In the plan are some rather ambitious goals, including funding ten new clinical trials in 2016. For much of the last year that has looked very ambitious indeed. But today the Board took a big step towards reaching that goal, approving three clinical trials focused on some deadly or life-threatening conditions.

The first is Forty Seven Inc.’s work targeting colorectal cancer, using a monoclonal antibody that can strip away the cancer cells ability to evade  the immune system. The immune system can then attack the cancer. But just in case that’s not enough they’re going to hit the tumor from another side with an anti-cancer drug called cetuximab. It’s hoped this one-two punch combination will get rid of the cancer.

Finding something to help the estimated 49,000 people who die of colorectal cancer in the U.S. every year would be no small achievement. The CIRM Board thought this looked so promising they awarded Forty Seven Inc. $10.2 million to carry out a clinical trial to test if this approach is safe. We funded a similar approach by researchers at Stanford targeting solid tumors in the lung and that is showing encouraging results.

Our Board also awarded $7.35 million to a team at Cedars-Sinai in Los Angeles that is using stem cells to treat pulmonary hypertension, a form of high blood pressure in the lungs. This can have a devastating, life-changing impact on a person leaving them constantly short of breath, dizzy and feeling exhausted. Ultimately it can lead to heart failure.

The team at Cedars-Sinai will use cells called cardiospheres, derived from heart stem cells, to reduce inflammation in the arteries and reduce blood pressure. CIRM is funding another project by this team using a similar  approach to treat people who have suffered a heart attack. This work showed such promise in its Phase 1 trial it’s now in a larger Phase 2 clinical trial.

The largest award, worth $20 million, went to target one of the rarest diseases. A team from UCLA, led by Don Kohn, is focusing on Adenosine Deaminase Severe Combined Immune Deficiency (ADA-SCID), which is a rare form of a rare disease. Children born with this have no functioning immune system. It is often fatal in the first few years of life.

The UCLA team will take the patient’s own blood stem cells, genetically modify them to fix the mutation that is causing the problem, then return them to the patient to create a new healthy blood and immune system. The team have successfully used this approach in curing 23 SCID children in the last few years – we blogged about it here – and now they have FDA approval to move this modified approach into a Phase 2 clinical trial.

So why is CIRM putting money into projects that it has either already funded in earlier clinical trials or that have already shown to be effective? There are a number of reasons. First, our mission is to accelerate stem cell treatments to patients with unmet medical needs. Each of the diseases funded today represent an unmet medical need. Secondly, if something appears to be working for one problem why not try it on another similar one – provided the scientific rationale and evidence shows it is appropriate of course.

As Randy Mills, our President and CEO, said in a news release:

“Our Board’s support for these programs highlights how every member of the CIRM team shares that commitment to moving the most promising research out of the lab and into patients as quickly as we can. These are very different projects, but they all share the same goal, accelerating treatments to patients with unmet medical needs.”

We are trying to create a pipeline of projects that are all moving towards the same goal, clinical trials in people. Pipelines can be horizontal as well as vertical. So we don’t really care if the pipeline moves projects up or sideways as long as they succeed in moving treatments to patients. And I’m guessing that patients who get treatments that change their lives don’t particularly

Ingenious CIRM-funded stem cell approach to treating ALS gets go-ahead to start clinical trial

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Clive Svendsen

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, was first identified way back in 1869 but today, more than 150 years later, there are still no effective treatments for it. Now a project, funded by CIRM, has been given approval by the Food and Drug Administration (FDA) to start a clinical trial that could help change that.

Clive Svendsen and his team at Cedars-Sinai are about to start a clinical trial they hope will help slow down the progression of the disease. And they are doing it in a particularly ingenious way. More on that in a minute.

First, let’s start with ALS itself. It’s a particularly nasty, rapidly progressing disease that destroys motor neurons, those are the nerve cells in the brain and spinal cord that control movement. People with ALS lose the ability to speak, eat, move and finally, breathe. The average life expectancy after diagnosis is just 3 – 4 years. It’s considered an orphan disease because it affects only around 30,000 people in the US; but even with those relatively low numbers that means that every 90 minutes someone in the US is diagnosed with ALS, and every 90 minutes someone in the US dies of ALS.

Ingenious approach

In this clinical trial the patients will serve as their own control group. Previous studies have shown that the rate of deterioration of muscle movement in the legs of a person with ALS is the same for both legs. So Svendsen and his team will inject specially engineered stem cells into a portion of the spine that controls movement on just one side of the body. Neither the patient nor the physician will know which side has received the cells. This enables the researchers to determine if the treated leg is deteriorating at a slower rate than the untreated leg.

The stem cells being injected have been engineered to produce a protein called glial cell line derived neurotrophic factor (GDNF) that helps protect motor neurons. Svendsen and the team hope that by providing extra GDNF they’ll be able to protect the motor neurons and keep them alive.

Reaching a milestone

In a news release announcing the start of the trial, Svendsen admitted ALS is a tough disease to tackle:

“Any time you’re trying to treat an incurable disease, it is a long shot, but we believe the rationale behind our new approach is strong.”

Diane Winokur, the CIRM Board patient advocate for ALS, says this is truly a milestone:

“In the last few years, thanks to new technologies, increased interest, and CIRM support, we finally seem to be seeing some encouraging signs in the research into ALS. Dr. Svendsen has been at the forefront of this effort for the 20 years I have followed his work.  I commend him, Cedars-Sinai, and CIRM.  On behalf of those who have suffered through this cruel disease and their families and caregivers, I am filled with hope.”

You can read more about Clive Svendsen’s long journey to this moment here.

 

Creating a “Pitching Machine” to speed up our delivery of stem cell treatments to patients

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When baseball players are trying to improve their hitting they’ll use a pitching machine to help them fine tune their stroke. Having a device that delivers a ball at a consistent speed can help a batter be more consistent and effective in their swing, and hopefully get more hits.

That’s what we are hoping our new Translating and Accelerating Centers will do. We call these our “Pitching Machine”, because we hope they’ll help researchers be better prepared when they apply to the Food and Drug Administration (FDA) for approval to start a clinical trial, and be more efficient and effective in the way they set up and run that clinical trial once they get approval.

The CIRM Board approved the Accelerating Center earlier this summer. The $15 million award went to QuintilesIMS, a leading integrated information and technology-enabled healthcare service provider.

The Accelerating Center will provide key core services for researchers who have been given approval to run a clinical trial, including:

  • Regulatory support and management services
  • Clinical trial operations and management services
  • Data management, biostatistical and analytical services

The reason why these kinds of service are needed is simple, as Randy Mills, our President and CEO explained at the time:

“Many scientists are brilliant researchers but have little experience or expertise in navigating the regulatory process; this Accelerating Center means they don’t have to develop those skills; we provide them for them.”

The Translating Center is the second part of the “Pitching Machine”. That is due to go to our Board for a vote tomorrow. This is an innovative new center that will support the stem cell research, manufacturing, preclinical safety testing, and other activities needed to successfully apply to the FDA for approval to start a clinical trial.

The Translating Center will:

  • Provide consultation and guidance to researchers about the translational process for their stem cell product.
  • Initiate, plan, track, and coordinate activities necessary for preclinical Investigational New Drug (IND)-enabling development projects.
  • Conduct preclinical research activities, including pivotal pharmacology and toxicology studies.
  • Manufacture stem cell and gene modified stem cell products under the highest quality standards for use in preclinical and clinical studies.

The two centers will work together, helping researchers create a comprehensive development plan for every aspect of their project.

For the researchers this is important in giving them the support they need. For the FDA it could also be useful in ensuring that the applications they get from CIRM-funded projects are consistent, high quality and meet all their requirements.

We want to do everything we can to ensure that when a CIRM-funded therapy is ready to start a clinical trial that its application is more likely to be a hit with the FDA, and not to strike out.

Just as batting practice is crucial to improving performance in baseball, we are hoping our “Pitching Machine” will raise our game to the next level, and enable us to deliver some game-changing treatments to patients with unmet medical needs.

 

Board gives stem cell institute marching orders, and a road map

The poet T. S. Eliot once wrote: “If you aren’t in over your head, how do you know how tall you are?” Well, everyone at CIRM, California’s stem cell institute, is about to find out how tall we are.

Strategic Plan coverYesterday our governing Board approved a new Strategic Plan. To call it ambitious might be considered an understatement. Among the goals it commits us to achieving are:

  • Funding 50 new clinical trials in 5 years including 10 for rare or orphan disorders and 5 in conditions affecting children
  • Fostering enactment of a new, more efficient federal regulatory approval process for stem cell treatments
  • Introducing 50 new therapeutic candidates or devices into the development pipeline
  • Reducing the time it takes to move a stem cell treatment from the earliest Discovery stage into a clinical trial by 50%
  • Increasing the number of projects moving to the next stage of development by 50%

No easy task

Each goal by itself might be considered challenging. Taken together they are likely to stretch us all. And yet that’s why we joined CIRM, why we feel fortunate to be part of this mission. We have a chance to be part of a movement that could change the face of medicine as we know it. We knew it wouldn’t be easy. But now we know what we have to do to help achieve that.

As Randy Mills, our President and CEO, said in a news release, the goal in developing this Strategic Plan was to create a clear vision for the next five years of the Institute:

”We have around $900 million left to work with and we wanted a plan that used that money to the best possible effect, maximizing our chances of pushing as many new treatments to patients as possible. We didn’t want something ‘good enough’, we wanted something ‘great’. This plan is extremely ambitious, but also realistic in the goals it sets out and the way those goals can be met.”

The Strategic Plan – you can read it in full here – doesn’t just lay out goals, it also creates a road map on how to meet those goals. They include engaging industry more, being more creative in how we move the most promising projects from one stage of research to the next, and finding ways to change the regulatory approval process to help remove obstacles and speed up the progress of these therapies into clinical trials.

Aiming high

We know we may not achieve all our goals. As Randy Mills said at our Board meeting: “This is a difficult plan. These goals are not easy to achieve.” There are always risks in pursuing something so big and ambitious but no one ever achieved anything truly worthwhile by playing it safe. We are not interested in playing it safe.

We may start out by being, as T. S. Eliot put it “in over our heads”. But we’re confident we’ll be able to grow tall enough to make this plan work.

As Randy Mills told the Board: “If we are all in this together then the probability of success is high, and if we are successful then all this would have been worthwhile.”

Faster, better, more efficient. Challenging? That too. An update on CIRM 2.0.

Changing direction is never easy. The greater the change the greater the likelihood you’ll have to make adjustments and do some fine-tuning along the way to make sure you get it right.

On January 1st of this year we made a big change, launching CIRM 2.0. Our President and CEO Dr. C. Randal Mills called it “a radical overhaul of the way the Agency does business.” This new approach puts the emphasis on patients, partnerships and speed and cuts down the time from application to funding of clinical-stage projects from around two years to just 120 days.

You can read more about 2.0 here.

So, several months into the program how are we doing?

Clinical stage of CIRM 2.0 has three programs

Clinical stage of CIRM 2.0 has three programs

Well, since January 1st we have had three application tracks under 2.0 that reflect our goal of accelerating therapies to patients with unmet medical needs. These focus on late stage work to either get a promising therapy into a clinical trial, to carry out a clinical trial, or to help a promising project move even faster.

Under those three programs we have had 12 applications for funding, for a total request of $111 million. With application deadlines the last business day of each month two of those were in January, two in February, three more in March and five in April.

As Dr. Mills told our governing Board when they met last week, that number is more than we were expecting:

 “When we started the program we calculated there’d be around one or two applications a month, not five. I don’t think having five applications a month is sustainable, but that’s probably just the backlog, the pent up demand for funding, working its way through the system. For now we can cope with that volume.”

Interestingly eight of those applications were for funding for clinical trials:

  • Two for Phase 1
  • One for Phase 2
  • Five for Phase 3

Last week our Board approved one of those Phase 3 trials (the last big hurdle to clear before the Food and Drug Administration will consider approving it for wider use), investing almost $18 million in NeoStem’s therapy for one of the deadliest forms of skin cancer, metastatic melanoma.

This is the first time we have ever funded a Phase 3 trial. So, quite a milestone for us. But it may well not be the last one. The Board also approved a project to conduct the late preclinical work needed to apply to conduct a trial in retinitis pigmentosa.

Dr. Mills said there are two clear patterns so far:

“We are getting a more mature portfolio of clinical stage programs for adjudication. We are also starting to see requests for accelerating activities, where we have made previous awards to researchers who now have identified new ways to accelerate that work and they are turning to us for help in doing that.”

Of the 12 applications received we have screened all of them within the 7-day target window to make sure they meet funding criteria. Some have been ruled out for not being within the scope of the award program. The accepted applications have all had budget reviews and been sent on for expert analysis within the slated time frames.

We had a couple of hiccups with our first review but that resulted from on-line technology and getting everyone comfortable with the new rules we were bringing in. The second review resulted in the first two awards by our Board last week, and the third review occurred yesterday.

“The bottom line is things are moving through and things are being weeded out. In March we had two clinical stage applications and one add-on funding application but that one add-on failed in screening. So, in general CIRM 2.0 is being well utilized. There’s no question we are significantly reducing application time from application to funding, attracting later stage applications. Clearly this has not been without its challenges but the team is doing a great job of managing everything.”

And remember this is only the first part of CIRM 2.0. We have two other programs, for Discovery or basic research and Translational research, that are being developed and we plan on rolling those out later this summer.

Stay tuned for more details on those programs.

Spiderman Sets the Tone for Stem Cell Agency Board Meeting

I don’t often think about Spiderman at meetings of our governing Board – no, really I don’t – but yesterday was an exception. Not that I was daydreaming, rather I was listening to our new President & CEO C. Randal Mills, Ph.D., talk about his determination to set a very specific tone in leading the agency.

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Randy had just explained to the Board that he had asked the agency’s General Counsel to draw up an agreement stating he – Randy, not the lawyer – will not accept a job with any company funded by CIRM for at least one year following his departure from the agency. In addition he will also refuse to accept gifts or travel payments from any company, institution or individual who receives agency funding.

In a news release we issued following the Board meeting he explained his reasons for making this commitment:

“I want the people of California to know that my sole interest in being at CIRM is to help advance stem cell treatments to patients who are in need. I will do so with a full commitment to transparency and by never compromising the integrity of our mission nor our trust to the taxpayers of California.”

And that’s where Spiderman comes in. As any fan of the movie or comic books can tell you one of the things Spiderman says a lot is “With great power comes great responsibility.”

In making his commitment Randy wanted to send a very clear and very strong message that he understands what his role as the President involves, and that it’s important for him to demonstrate that through his actions.

Board member and patient advocate, Sherry Lansing, echoed that saying:

“We take even the possibility of a perception of a conflict of interest very seriously and are determined to do whatever is necessary to ensure that we protect the reputation of the agency and the work that we do. We fully support Dr. Mills in the way he is handling this issue.”

Randy decided to make that commitment after his predecessor, Dr. Alan Trounson joined the Board of Stem Cells Inc., a company that we awarded more than $19 million to develop a therapy for Alzheimer’s disease. While there is nothing illegal about Dr. Trounson’s actions the news did cause a bit of a stir with a few commentators saying this was a dark mark against the agency – even though there is nothing we could have done to stop it because we did not know it was happening.

Randy is not asking anyone else to make the same commitment he has made, but he says it was important for him to do so. His role as President & CEO carries great responsibility and he says he wants to show that he takes it very seriously and will lead by example.

I rather think Spiderman would approve.

Kevin McCormack