CIRM 2.0

A model for success

/ Kevin McCormack / Leave a comment
Dr. Maria Millan, CIRM’s President & CEO

Funding models are rarely talked about in excited tones.  It’s normally relegated to the dry tomes of academia. But in CIRM’s case, the funding model we have created is not just fundamental to our success in advancing regenerative medicine in California, it’s also proving to be a model that many other agencies are looking at to see if they can replicate it.

A recent article in the journal Cell & Gene Therapy Insights looks at what the CIRM model does and how it has achieved something rather extraordinary.

Full disclosure. I might be a tad biased here as the article was written by my boss, Dr. Maria Millan, and two of my colleagues, Dr. Sohel Talib and Dr. Shyam Patel.

I won’t go into huge detail here (you can get that by reading the article itself) But the article “highlights 3 elements of CIRM’s funding model that have enabled California academic researchers and companies to de-risk development of novel regenerative medicine therapies and attract biopharma industry support.”

Those three elements are:

1. Ensuring that funding mechanisms bridge the entire translational “Valley of Death”

2. Constantly optimizing funding models to meet the needs of a rapidly evolving industry

3. Championing the portfolio and proactively engaging potential industry partners

As an example of the first, they point to our Disease Team awards. These were four-year investments that gave researchers with promising projects the time, support and funds they needed to not only develop a therapy, but also move it out of academia into a company and into patients.  Many of these projects had struggled to get outside investment until CIRM stepped forward. One example they offer is this one.

“CIRM Disease Team award funding also enabled Dr. Irving Weissman and the Stanford University team to discover, develop and obtain first-in-human clinical data for the innovative anti-CD47 antibody immunotherapy approach to cancer. The spin-out, Forty Seven, Inc., then leveraged CIRM funding as well as venture and public market financing to progress clinical development of the lead candidate until its acquisition by Gilead Sciences in April 2020 for $4.9B.”

But as the field evolved it became clear CIRM’s funding model had to evolve too, to better meet the needs of a rapidly advancing industry. So, in 2015 we changed the way we worked. For example, with clinical trial stage projects we reduced the average time from application to funding from 22 months to 120 days. In addition to that applications for new clinical stage projects were able to be submitted year-round instead of only once or twice a year as in the past.

We also created hard and fast milestones for all programs to reach. If they met their milestone funding continued. If they didn’t, funding stopped. And we required clinical trial stage projects, and those for earlier stage for-profit companies, to put up money of their own. We wanted to ensure they had “skin in the game” and were as committed to the success of their project as we were.

Finally, to champion the portfolio we created our Industry Alliance Program. It’s a kind of dating program for the researchers CIRM funds and companies looking to invest in promising projects. Industry partners get a chance to look at our portfolio and pick out projects they think are interesting. We then make the introductions and see if we can make a match.

And we have.

“To date, the IAP has also formally enrolled 8 partners with demonstrated commitment to cell and gene therapy development. The enrolled IAP partners represent companies both small and large, multi-national venture firms and innovative accelerators.

Over the past 18 months, the IAP program has enabled over 50 one-on-one partnership interactions across CIRM’s portfolio from discovery stage pluripotent stem cell therapies to clinical stage engineered HSC therapies.”

As the field continues to mature there are new problems emerging, such as the need to create greater manufacturing capacity to meet the growth in demand for high quality stem cell products. CIRM, like all other agencies, will also have to evolve and adapt to these new demands. But we feel with the model we have created, and the flexibility we have to pivot when needed, we are perfectly situated to do just that.

Encouraging news about CIRM-funded clinical trial targeting vision loss

/ Kevin McCormack / 3 Comments

dry AMD

An eye affected by dry age-related macular degeneration

Dry age-related macular degeneration (AMD) is the leading cause of vision loss in the U.S. By 2020 it’s estimated that as many as three million Americans will be affected by the disease. Right now, there is no effective therapy. But that could change. A new CIRM-funded clinical trial is showing promise in helping people battling the disease not just in stabilizing their vision loss, but even reversing it.

In AMD, cells in the retina, the light-sensitive tissue at the back of the eye, are slowly destroyed affecting a person’s central vision. It can make it difficult to do everyday activities such as reading or watching TV and make it impossible for a person to drive.

Researchers at the University of Southern California (USC) Roski Eye Institute at the Keck School of Medicine, and Regenerative Patch Technologies, have developed a therapy using embryonic stem cells that they turned into retinal pigment epithelium (RPE) cells – the kind of cell destroyed by AMD. These cells were then placed on a synthetic scaffold which was surgically implanted in the back of the eye.

Imaging studies showed that the RPE cells appeared to integrate well into the eye and remained in place during follow-up tests 120 to 365 days after implantation.

Encouraging results

Of the five patients enrolled in the Phase 1/2a trial, four maintained their vision in the treated eye, two showed improvement in the stability of their vision, and one patient had a 17-letter improvement in their vision on a reading chart. In addition, there were no serious side effects or unanticipated problems.

There were other indications the implants were proving beneficial.  People with normal vision have the ability to focus their gaze on a single location. People with advanced AMD lose that ability. In this trial, two of the patients recovered stable fixation. These improvements were maintained in follow-up tests.

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Abla Creasey, Ph.D., CIRM’S Vice President of Therapeutics and Strategic Infrastructure says even these small benefits are important:

“Having a therapy with a favorable safety profile, that could slow down the progression, or even reverse the vision loss would benefit millions of Americans. That’s why these results, while still in an early stage are encouraging, because the people treated in the trial are ones most severely affected by the disease who have the least potential for visual recovery.”

This study reflects CIRM’s long-term commitment to supporting the most promising stem cell research. The Stem Cell Agency began supporting USC’s Dr. Mark Humayun, the lead inventor of the implant, in 2010 and has been a partner with him and his team since then.

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In a news release Dr. Humayun said they plan to recruit another 15 patients to see if these results hold up:

“Our study shows that this unique stem cell–based retinal implant thus far is well-tolerated, and preliminary results suggest it may help people with advanced dry age-related macular degeneration.”

While the results, published in the journal Science Translational Medicine, are encouraging the researchers caution that this was a very early stage clinical trial, with a small number of patients. They say the next step is to continue to follow the four patients treated in this trial to see if there are any further changes to their vision, and to conduct a larger trial.

 

 

Getting faster, working smarter: how changing the way we work is paying big dividends

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This blog is part of the Month of CIRM series

Speeding up the way you do things isn’t always a good idea. Just ask someone who got a ticket for going 65mph in a 30mph zone. But at CIRM we have found that doing things at an accelerated pace is paying off in a big way.

When CIRM started back in 2004 we were, in many ways, a unique organization. That meant we pretty much had to build everything from scratch, creating our own ways of asking for applications, reviewing those applications, funding them etc. Fast forward ten years and it was clear that, as good a job as we did in those early days, there was room for improvement in the way we operated.

So we made some changes. Big changes.

We adopted as our mantra the phrase “operational excellence.” It doesn’t exactly trip off the tongue but it does reflect what we were aiming for. The Business Dictionary defines operational excellence as:

 “A philosophy of the workplace where problem-solving, teamwork, and leadership results in the ongoing improvement in an organization.”

We didn’t want to just tinker with the way we worked, we wanted to reinvent every aspect of our operation. To do that we involved everyone in the operation. We held a series of meetings where everyone at CIRM, and I do mean everyone, was invited to join in and offer their ideas on how to improve our operation.

CIRM2.0_Logo

The end result was CIRM 2.0. At the time we described it as “a radical overhaul” of the way we worked. That might have been an understatement. We increased the speed, frequency and volume of the programs we offered, making it easier and more predictable for researchers to apply to us for funding, and faster for them to get that funding if they were approved.

For example, before 2.0 it took almost two years to go from applying for funding for a clinical trial to actually getting that funding. Today it takes around 120 days.

But it’s not just about speed. It’s also about working smarter. In the past if a researcher’s application for funding for a clinical trial failed it could be another 12 months before they got a chance to apply again. With many diseases 12 months could be a death sentence. So we changed the rules. Now if you have a project ready for a clinical trial you can apply any time. And instead of recommending or not recommending a project, basically voting it up or down, our independent panel of expert reviewers now give researchers with good but not great applications constructive feedback, enabling the researchers to make the changes needed to improve their project, and reapply for funding within 30 days.

This has not only increased the number of applications for clinical trials, it has also increased the quality of those applications.

We made similar changes in our Discovery and Translation programs. Increasing the frequency of each award, making it easier for researchers to know when the next round of funding was coming up. And we added incentives to encourage researchers to move successful projects on to the next level. We wanted to create a pipeline of the most promising projects steadily moving towards the clinic.

The motivation to do this comes from our patients. At CIRM we are in the time business. Many of the patients who are looking to stem cells to help them don’t have the luxury of time; they are rapidly running out of it. So we have a responsibility to do all we can to reduce the amount of time it takes to get the most promising therapies to them, without in any way compromising safety and jeopardizing their health.

By the end of 2016 those changes were very clearly paying dividends as we increased the frequency of reviews and the number of projects we reviewed but at the same time decreased the amount of time it took us to do all that.

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But we are not done yet. We have done a good job of improving the way we work. But there is always room to be even better, to go even faster and be more efficient.

We are not done accelerating. Not by a long shot.

Emotions and gratitude at changing of the guard at Stem Cell Agency

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RandyFarewellFamily

Randy Mills and his family

Randy, as regular readers of this blog know, is, or rather was, the President and CEO of CIRM. James Harrison is less well known to the outside world but his imprint on CIRM, as our General Counsel and one of the key figures behind Proposition 71, is even bigger than that of Randy’s.

Randy came to the stem cell agency a little over three years ago and in pretty quick order completely refashioned us. Under his guidance CIRM 2.0 became a sleek, streamlined funding machine, turning what had been an almost two-year process from application to funding into one that took just 120 days. He revamped the frequency with which we offered specific programs, making it more predictable and so easier for researchers to know when the next round was coming up. He helped usher in a new Strategic Plan that is a blueprint for us until 2020.

But the changes he implemented were not just about the way we worked, it was also about how we worked and particularly how we worked together. He turned the agency into a true team, one where everyone felt they not only had a role to play but that what they did was important in determining the success of the agency.

Not surprisingly there was no shortage of people ready to praise him. CIRM Board Chair Jonathan Thomas (JT) thanked Randy for turning the agency around, transforming it into an organization that even the National Institutes of Health (NIH) now looks to as a model (more on that in a subsequent blog). Vice Chair Art Torres thanked Randy for his leadership and for his compassion toward patients, always putting them first in everything that he and the agency did. Board member Sherry Lansing called Randy “a genius and visionary”.

But perhaps the most moving tributes came from patients advocates.

Don Reed said; “When I first met Randy I didn’t like him. I thought CIRM was one of the best, if not the best, organization out there and who was this person to say they were going to come in and make it better. Well, you did Randy and we are all so very grateful to you for that.”

Adrienne Shapiro from Axis Advocacy, an organization dedicated to finding a cure for sickle cell disease, presented Randy with the “Heart of a Mother” award, thanking him for his tireless support of patients and their families.

Jake Javier, a participant in the Asterias spinal cord injury trial, wrote a note saying: “You positively affect so many through your amazing funding efforts for life changing research, and should be very proud of that. But something I will always remember is how personal and genuine you were while doing it. I hope you got the chance to meet as many of the people you helped as possible because I know they would remember the same.”

Randy – who is leaving to become President/CEO of the National Marrow Donor/Be The Match program – was clearly deeply moved by the tributes, but reminded everyone that he was leaving us in good hands. The Board named Dr. Maria Millan as the interim President and CEO, pending a meeting of a search committee to determine the steps for appointing a permanent replacement.

Randy praised Maria for her intelligence, compassion and vision:

“Maria Millan has been a great partner in all that we have achieved at CIRM. She was a key part of developing the Strategic Plan; she  understands it inside out and has been responsible for administering it. She is a wonderful leader and is going to be absolutely phenomenal.”

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James Harrison (left) with CIRM Board members Jonathan Thomas and Bert Lubin

The tributes for James Harrison were ever bit as moving. James has been a part of CIRM since before there was a CIRM. He helped draft Proposition 71, the ballot initiative that created the stem cell agency, and has played a key role since as General Counsel.

JT: “James has been a part of literally every decision and move that CIRM has made in its entire history. He’s been integral in everything. When I first came to CIRM, I was told by Bob Klein (JT’s predecessor as Chair) ‘Don’t brush your teeth without checking with James first’ suggesting a level of knowledge and expertise that was admirable.”

Jeff Sheehy “We would not be here without James. He organized the defense when we were sued by our opponents in the early days, through the various leadership challenges we had, all of the legal difficulties we had James was there to guide us and it’s been nothing short of extraordinary. Your brilliance and steadiness is amazing. While we are screaming and pulling our hair out there was James. Just saying his name makes me feel more relaxed.”

Sherry Lansing: “One thing I never worried about was our ethics, because you protected us at all times. You have such strong ethical values, you are always calm and rational and no matter what was going on you were always the rock who could explain things to everyone and deal with it with integrity.”

James is leaving to take a more active role in the law firm Remcho, Johansen & Purcell, where he is partner. Succeeding him as General Counsel is Scott Tocher, who has been at CIRM almost as long as James.

Randy; “To have someone like Scott come in and replace someone who wrote Proposition 71 speaks for the bench strength of the agency and how we are in very good hands.”

Art Torres joked “Scott has been waiting as long as Prince Charles has to take over the reins and we’re delighted to be able to work with him.”

We wish Randy and James great good luck in their next adventures.

 

Cured by Stem Cells

/ Kevin McCormack / 1 Comment

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To get anywhere you need a good map, and you need to check it constantly to make sure you are still on the right path and haven’t strayed off course. A year ago the CIRM Board gave us a map, a Strategic Plan, that laid out our course for the next five years. Our Annual Report for 2016, now online, is our way of checking that we are still on the right path.

I think, without wishing to boast, that it’s safe to say not only are we on target, but we might even be a little bit ahead of schedule.

The Annual Report is chock full of facts and figures but at the heart of it are the stories of the people who are the focus of all that we do, the patients. We profile six patients and one patient advocate, each of whom has an extraordinary story to tell, and each of whom exemplifies the importance of the work we support.

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Brenden Whittaker: Cured

Two stand out for one simple reason, they were both cured of life-threatening conditions. Now, cured is not a word we use lightly. The stem cell field has been rife with hyperbole over the years so we are always very cautious in the way we talk about the impact of treatments. But in these two cases there is no need to hold back: Evangelina Padilla Vaccaro and Brenden Whittaker have been cured.

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Evangelina: Cured

 

In the coming weeks we’ll feature our conversations with all those profiled in the Annual Report, giving you a better idea of the impact the stem cell treatments have had on their lives and the lives of their family. But today we just wanted to give a broad overview of the Annual Report.

The Strategic Plan was very specific in the goals it laid out for us. As an agency we had six big goals, but each Team within the agency, and each individual within those teams had their own goals. They were our own mini-maps if you like, to help us keep track of where we were individually, knowing that every time an individual met a goal they helped the Team get closer to meeting its goals.

As you read through the report you’ll see we did a pretty good job of meeting our targets. In fact, we missed only one and we’re hoping to make up for that early in 2017.

But good as 2016 was, we know that to truly fulfill our mission of accelerating treatments to patients with unmet medical needs we are going to have do equally well, if not even better, in 2017.

That work starts today.

 

A look back at the last year – but with our eyes firmly on the future

/ Kevin McCormack / 3 Comments

Randy

CIRM President & CEO Randy Mills doesn’t want “good”, he wants “better”

Better.

With that single word Randy Mills, our President and CEO, starts and ends his letter in our 2015 Annual Report and lays out the simple principle that guides the way we work at CIRM.

Better.

But better what?

“Better infrastructure to translate early stage ideas into groundbreaking clinical trials. Better regulatory practices to advance promising stem cell treatments more efficiently. Better treatments for patients in need.”

“Better” is also the standard everyone at CIRM holds themselves to. Getting better at what we do so we can fulfill our mission of accelerating stem cell treatments to patients with unmet medical needs.

The 2015 Annual Report highlights the achievements of the last year, detailing how we invested $135 million in 47 different projects at all levels of research. How our Board unanimously passed our new Strategic Plan, laying out an ambitious series of goals for the next five years from funding 50 new clinical trials, to creating a new regulatory process for stem cell therapies.

Snapshot of CIRM's 2015 Funding

The report offers a snapshot of where our money has gone this year, and how much we have left. It breaks down what percentage of our funding has gone to different diseases and how much we have spent on administration.

Jonathan Thomas, the Chair of our Board, takes a look back at where we started, 10 years ago, comparing what we did then (16 awards for a total of $12.5 million) to what we are doing today. His conclusion; we’re doing better.

But we still have a long way to go. And we are determined to get even better.

P.S. By the way we are changing the way we do our Annual Report. Our next one will come out on January 1, 2017. We figured it just made sense to take a look back at the last year as soon as the new year begins. It gives you a better (that word again) sense of what we did and where we  are heading. So look out for that, coming sooner than you think.

CIRM Board targets diabetes and kidney disease with big stem cell research awards

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diabetes2

A recent study  estimated there may be more than 500 million people worldwide who have diabetes. That’s an astounding figure and makes diabetes one of the largest chronic disease epidemics in human history.

One of the most serious consequences of untreated or uncontrolled diabetes is kidney damage. That can lead to fatigue, weakness, confusion, kidney failure and even death. So two decisions taken by the CIRM Board today were good news for anyone already suffering from either diabetes or kidney disease. Or both.

The Board awarded almost $10 million to Humacyte to run a Phase 3 clinical trial of an artificial vein needed by people undergoing hemodialysis – that’s the most common form of dialysis for people with kidney damage. Hemodialysis helps clean out impurities and toxins from the blood. Without it waste will build up in the kidneys with devastating consequences.

The artificial vein is a kind of bioengineered blood vessel. It is implanted in the individual’s arm and, during dialysis, is connected to a machine to move the blood out of the body, through a filter, and then back into the body. The current synthetic version of the vein is effective but is prone to clotting and infections, and has to be removed regularly. All this puts the patient at risk.

Humacyte’s version – called a human acellular vessel or HAV – uses human cells from donated aortas that are then seeded onto a biodegradable scaffold and grown in the lab to form the artificial vein. When fully developed the structure is then “washed” to remove all the cellular tissue, leaving just a collagen tube. That is then implanted in the patient, and their own stem cells grow onto it, essentially turning it into their own tissue.

In earlier studies Humacyte’s HAV was shown to be safer and last longer than current versions. As our President and CEO, Randy Mills, said in a news release, that’s clearly good news for patients:

“This approach has the potential to dramatically improve our ability to care for people with kidney disease. Being able to reduce infections and clotting, and increase the quality of care the hemodialysis patients get could have a significant impact on not just the quality of their life but also the length of it.”

There are currently almost half a million Americans with kidney disease who are on dialysis. Having something that makes life easier, and hopefully safer, for them is a big plus.

The Humacyte trial is looking to enroll around 350 patients at three sites in California; Sacramento, Long Beach and Irvine.

While not all people with diabetes are on dialysis, they all need help maintaining healthy blood sugar levels, particularly people with type 1 diabetes. That’s where the $3.9 million awarded to ViaCyte comes in.

We’re already funding a clinical trial with ViaCyte  using an implantable delivery system containing stem cell-derived cells that is designed to measure blood flow, detect when blood sugar is low, then secrete insulin to restore it to a healthy level.

This new program uses a similar device, called a PEC-Direct. Unlike the current clinical trial version, the PEC-Direct allows the patient’s blood vessels to directly connect, or vasularize, with the cells inside it. ViaCyte believes this will allow for a more robust engraftment of the stem cell-derived cells inside it and that those cells will be better able to produce the insulin the body needs.

Because it allows direct vascularization it means that people who get the delivery system  will also need to get chronic immune suppression to stop their body’s immune system attacking it. For that reason it will be used to treat patients with type 1 diabetes that are at high risk for acute complications such as severe hypoglycemic (low blood sugar) events associated with hypoglycemia unawareness syndrome.

In a news release Paul Laikind, Ph.D., President and CEO of ViaCyte, said this approach could help patients most at risk.

“This high-risk patient population is the same population that would be eligible for cadaver islet transplants, a procedure that can be highly effective but suffers from a severe lack of donor material. We believe PEC-Direct could overcome the limitations of islet transplant by providing an unlimited supply of cells, manufactured under cGMP conditions, and a safer, more optimal route of administration.”

The Board also approved more than $13.6 million in awards under our Discovery program. You can see the winners here.

 

Accelerating the drive for new stem cell treatments

/ Kevin McCormack / 1 Comment

Acceleration

Acceleration is defined as the “increase in the rate or speed of something.” For us that “something” is new stem cell treatments for patients with unmet medical needs. Today our governing Board just approved a $15 million partnership with Quintiles to help us achieve that acceleration.

Quintiles was awarded the funding to create a new Accelerating Center. The goal of the center is to give stem cell researchers the support they need to help make their clinical trials successful.

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

randy-at-podium1CIRM President Randy Mills addresses the CIRM Board

“Many scientists are brilliant researchers but have little experience or expertise in running a clinical trial; this Accelerating Center means they don’t have to develop those skills; we provide them for them. This partnership with Quintiles means that scientists don’t have to learn how to manage patient enrollment or how to create a data base to manage the results. Instead they are free to focus on what they do best, namely science.”

How does it work? Well, if a researcher has a promising therapy and approval from the US Food and Drug Administration (FDA) to start a clinical trial, the Accelerating Center helps them get that trial off the ground. It helps them find the patients they need, get those patients consented and ready for the trial, and then helps manage the trial and the data from the trial.

The devil is in the details

Managing those details can be a key factor in determining whether a clinical trial is going to be successful. Last year, a study in the New England Journal of Medicine listed the main reasons why clinical trials fail.

Among the reasons are:

  • Poor study design: Selecting the wrong patients, the wrong dosing and the wrong endpoint, as well as bad data and bad site management cause severe problems.
  • Poor management: A project manager who does not have enough experience in costing and conducting clinical trials will lead to weak planning, with no clear and real timelines, and to ultimate failure.

We hope our partnership with Quintiles in this Accelerating Center will help researchers avoid those and the other pitfalls. As the world’s largest provider of biopharmaceutical development and commercial outsourcing services, Quintiles has a lot of experience and expertise in this area. On its Twitter page it’s slogan is “Better, smarter, faster trials” so I think we made a smart choice.

When Randy Mills first pitched this idea to the Board, he said that he is a great believer in “not asking fish to learn how to fly, they should just do what they do best”.

The Accelerating Center means scientists can do what they do best, and we hope that leads to what patients need most; treatments and cures.

Related Links:

Why is a cell therapy that restores sight to the blind against the law?

/ Kevin McCormack / 5 Comments

FDA

A lot of people are frustrated with the US Food and Drug Administration (FDA) and its woefully slow process for approving stem cell therapies. That’s one of the reasons why we started the CIRM Stem Cell Champions campaign, to gather as many like-minded supporters of stem cell research as possible and help to change the way the FDA works, to create a more efficient approval process.

You can read more about that campaign and watch a short video on what being a Stem Cell Champion involves (hint: not very much).

Now Randy Mills, our President and CEO, has teamed up with former US Senator Bill Frist to explain precisely why the FDA needs to change the way it regulates stem cells, and to offer a simple way to create the system that will best serve the needs of patients.

This Op Ed appeared on Fox News’ online Opinion section on Friday, May 20th.

Cell therapy reversed blindness for 47,000 patients in 2015. So why is it against the law?

By C. Randal Mills Ph.D., Sen. Bill Frist M.D.

As medical miracles go, restoring sight to the blind is right up there. A mother seeing her baby for the first time, or a child being able to count the stars is a beautiful gift, and its value cannot be overstated. Last year 47,000 Americans received that gift and had their blindness reversed through the transplantation of cells from a corneal donor’s final selfless act.

It is safe, it is effective, and because it is curative, it is a relatively cost effective procedure. It is medicine at its most beautiful. And according to FDA regulations, the distribution of this cell therapy is in violation of federal law.

That’s right. The regulation says that no matter how competent the surgeon, the FDA must first approve cells from donated corneas as if they were a drug—a process that takes over a decade and can costs billions of dollars — all for a practice that has been successfully restoring sight for more than 50 years. And this is only one example.

The good news: the FDA doesn’t always adhere to its regulations and has not in this case.

The bad news: inconsistent enforcement creates uncertainty, deterring innovation for other unmet medical needs such as arthritis, back pain, and diabetic ulcers.

How did a country known for pioneering medical breakthroughs get here?

Appropriate regulation of living cells that treat disease is inherently complex. Some therapies, like corneal cell transplants, are well-understood. Others are far more sophisticated and can involve forcing cells to change from one type to another, cutting out defective genes, and growing cells in culture to expand their numbers into the billions. Although this may sound like science fiction, it’s the type of very real science that will revolutionize the practice of medicine. And it is a challenging spectrum to regulate.

Unfortunately, what we have today amounts to a regulatory light switch for cell therapy; one that is either OFF or ON. For some cell therapies there is essentially no pre-market regulation. But at some point of added complexity, often arbitrarily decided by the FDA, the switch flips to ON and the cell becomes a drug in the minds of the Agency. And the consequences could not be more profound.

A product can be introduced through the OFF pathway in days with no FDA review and at very little cost. The ON pathway on the other hand, takes 10-20 years and can cost over a billion dollars. For cell therapy, there is no in between.

It is not possible to regulate the continuum of cell therapies fairly and effectively by using this binary approach. The system is broken and is impeding the hunt for safe and effective treatments for suffering patients.

Why? Because sensible people don’t invest significant capital gambling that the FDA will give them a pass out of its rules. They evaluate the time and cost of development assuming they will be forced down the ON pathway. They also assume that this arbitrary approach to regulation will (and often does) work against them by allowing a competitor to enter the market through the OFF pathway, placing them at a prohibitive disadvantage. The results speak for themselves. After 15 years under this paradigm we have had only a few cell therapies approved, all commercial disasters.

This is because the ON-OFF approach fails to adequately account for the difference in cell therapy complexity. To better understand, imagine this methodology applied to the regulation of automobiles. The government might permit low tech cars, say the Model T, to be sold without pre-market regulation. But if a manufacturer wanted to improve the vehicle by adding air conditioning, a radio or other such feature, the car would be subject to massive pre-market regulation. And not just on the new feature. Instead, the addition of the new feature would trigger a bumper-to-bumper evaluation of the entire car, increasing its development cost from basically nothing to that of a Lamborghini. The result would be streets full of hot, radio-less go-karts, except for a few ultra-high-end sports cars whose manufacturers are now defunct because they were never able to recoup the disproportionate costs of satisfying the regulatory system. This is what we see with cell therapies today: progress that is sluggish at best.

How can we move forward?

Ironically, the FDA identified a solution to the problem. In order to account for the broad spectrum inherent to cell therapy, in the late 90’s the FDA proposed a progressive, risk-based approach. The higher the risk, the greater the regulation. This guards against under regulation that might put patients at risk and prevents overregulation that can disincentivize the development of new or improved products.

In the FDA’s own words, the regulation they proposed would abide by a few basic principles:

  • “Under this tiered, risk-based approach, we propose to exert only the type of government regulation necessary to protect the public health.”
  • “The regulation of different types of human cells… will be commensurate with the public health risks…”
  • “These planned improvements will increase the safety of human cells… while encouraging the development of new products.”

It was a remarkably common sense approach that would have balanced safety with the need for innovation over an exceptionally broad range of technological complexity and risk.

It would have.

Unfortunately, the regulatory framework that was promised was never delivered, and it is time to resuscitate it. The burden placed on the development of cell therapies must accurately reflect the risks; must be balanced against the very real consequences of doing nothing (patients continuing to suffer); and must be consistently and fairly applied. In short, the FDA had it right and we need to give them the tools to deliver the regulatory paradigm they originally envisioned.

If we fix this highly fixable problem, we can create a system that will drive new innovations and better outcomes. Europe and Japan have already acted and are seeing the benefits. People with great ideas are coming off the bench, and game changing therapies are entering practice. While challenging the status quo does not sit well with some, particularly those who stand to prosper from the built-in barriers to entry the current structure provides, in the United States we have a responsibility to do better for patients and fix this broken system.

Randal Mills, Ph.D., is the President and CEO of the California Institute for Regenerative Medicine

William “Bill” H. Frist, M.D. is a nationally-acclaimed heart and lung transplant surgeon, former U.S. Senate Majority Leader, and chairman of the Executive Board of the health service private equity firm Cressey & Company.

What’s the big idea? Or in this case, what’s the 19 big ideas?

/ Kevin McCormack / 1 Comment

supermarket magazineHave you ever stood in line in a supermarket checkout line and browsed through the magazines stacked conveniently at eye level? (of course you have, we all have). They are always filled with attention-grabbing headlines like “5 Ways to a Slimmer You by Christmas” or “Ten Tips for Rock Hard Abs” (that one doesn’t work by the way).

So with those headlines in mind I was tempted to headline our latest Board meeting as: “19 Big Stem Cell Ideas That Could Change Your Life!”. And in truth, some of them might.

The Board voted to invest more than $4 million in funding for 19 big ideas as part of CIRM’s Discovery Inception program. The goal of Inception is to provide seed funding for great, early-stage ideas that may impact the field of human stem cell research but need a little support to test if they work. If they do work out, the money will also enable the researchers to gather the data they’ll need to apply for larger funding opportunities, from CIRM and other institutions, in the future

The applicants were told they didn’t have to have any data to support their belief that the idea would work, but they did have to have a strong scientific rational for why it might

As our President and CEO Randy Mills said in a news release, this is a program that encourages innovative ideas.

Randy Mills, Stem Cell Agency President & CEO

Randy Mills, CIRM President & CEO

“This is a program supporting early stage ideas that have the potential to be ground breaking. We asked scientists to pitch us their best new ideas, things they want to test but that are hard to get funding for. We know not all of these will pan out, but those that do succeed have the potential to advance our understanding of stem cells and hopefully lead to treatments in the future.”

So what are some of these “big” ideas? (Here’s where you can find the full list of those approved for funding and descriptions of what they involve). But here are some highlights.

Alysson Muotri at UC San Diego has identified some anti-retroviral drugs – already approved by the Food and Drug Administration (FDA) – that could help stop inflammation in the brain. This kind of inflammation is an important component in several diseases such as Alzheimer’s, autism, Parkinson’s, Lupus and Multiple Sclerosis. Alysson wants to find out why and how these drugs helps reduce inflammation and how it works. If he is successful it is possible that patients suffering from brain inflammation could immediately benefit from some already available anti-retroviral drugs.

Stanley Carmichael at UC Los Angeles wants to use induced pluripotent stem (iPS) cells – these are adult cells that have been genetically re-programmed so they are capable of becoming any cell in the body – to see if they can help repair the damage caused by a stroke. With stroke the leading cause of adult disability in the US, there is clearly a big need for this kind of big idea.

Holger Willenbring at UC San Francisco wants to use stem cells to create a kind of mini liver, one that can help patients whose own liver is being destroyed by disease. The mini livers could, theoretically, help stabilize a person’s own liver function until a transplant donor becomes available or even help them avoid the need for liver transplantation in the first place. Considering that every year, one in five patients on the US transplant waiting list will die or become too sick for transplantation, this kind of research could have enormous life-saving implications.

We know not all of these ideas will work out. But all of them will help deepen our understanding of how stem cells work and what they can, and can’t, do. Even the best ideas start out small. Our funding gives them a chance to become something truly big.

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