CIRM applauds FDA crackdown on stem cell clinics that “peddle unapproved treatments.”

FDA

CIRM is commending the US Food and Drug Administration (FDA) for its action against two stem cell clinics offering unapproved therapies.

On Wednesday, the FDA filed two complaints in federal court seeking a permanent injunction against California Stem Cell Treatment Center Inc. and US Stem Cell Clinic LLC. of Sunrise, Florida. The FDA says the clinics are marketing stem cell products without FDA approval and are not complying with current good manufacturing practice requirements.

“We strongly support the FDA’s strong stance to seek judicial action to stop these  clinics from marketing unproven therapies that pose a threat to the safety of patients” says Maria T. Millan, M.D., CIRM’s President and CEO. “We agree with FDA Commissioner Dr. Scott Gottlieb’s statement that these ‘bad actors leverage the scientific promise of this field to peddle unapproved treatments that put patients’ health at risk.’”

In his statement yesterday, Dr. Gottlieb denounced the clinics saying they are exploiting patients and causing some of them “serious and permanent harm.”

“In the two cases filed today, the clinics and their leadership have continued to disregard the law and more importantly, patient safety. We cannot allow unproven products that exploit the hope of patients and their loved ones. We support sound, scientific research and regulation of cell-based regenerative medicine, and the FDA has advanced a comprehensive policy framework to promote the approval of regenerative medicine products. But at the same time, the FDA will continue to take enforcement actions against clinics that abuse the trust of patients and endanger their health.”

At CIRM, we believe it is critically important for participants in stem cell treatments to be fully informed about the nature of the therapy they are receiving, including whether it is approved by the FDA. Last year we partnered with California State Senator Ed Hernandez to pass Senate Bill No. 512, which required all clinics offering unproven stem cell therapies to post notices warning patients they were getting a therapy that was not approved by the FDA.

The Stem Cell Agency has taken several other actions to protect people seeking legitimate stem cell therapies.

  • All the clinical trials we consider for funding must already have an active Investigational New Drug (IND) status with the FDA and go through a rigorous scientific review by leading experts.
  • All CIRM-funded trials must adhere to strict regulatory standards and safety monitoring.
  • We have created the CIRM Alpha Stem Cell Clinics, a network of six top California medical centers that specialize in delivering patient-centered stem cell clinical trials that meet the highest standards of care and research.
  • CIRM provides access to information on all the clinical trials it supports.

“Through its funding mechanism, active partnership and infrastructure programs, CIRM has shepherded 48 FDA regulated, scientifically sound, rigorously reviewed promising stem cell and regenerative medicine projects into clinical trials,” says Dr. Millan. “Some of these treatment protocols have already started to show preliminary signs of benefit for debilitating and life-threatening disorders. We are committed to doing all we can, in partnership with patients, the research community and with the FDA, to develop transformative treatments for patients with unmet medical needs while adhering to the highest standards to protect the health and safety of patients and the public.”

To help people make informed decisions we have created an infographic and video that detail the information people need to know, and the questions they should ask, before they agree to participate in a clinical trial or get a stem cell therapy.

 

 

If you’re into stem cell manufacturing, this is the conference for you!

GMP cells

Manufacturing stem cells: Photo courtesy of Pluristem

Fulfilling CIRM’s mission doesn’t just mean accelerating promising stem cell treatments to patients. It also involves accelerating the whole field of regenerative medicine, which involves not just research, but developing candidate treatments, manufacturing cell therapies, and testing these therapies in clinical trials.

Manufacturing and the pre-clinical safety evaluation of cell therapies are topics that don’t always receive a lot of attention, but they are essential and crucial steps in bringing cell therapies to market. Manufacturing cells that meet the strict standards for use in human trials is often a bottleneck where different methods of making pluripotent stem cells (PSCs) are used and standardization is not readily possible.

Abla-8Abla Creasey, Vice President of Therapeutics and Strategic Infrastructure at CIRM, notes:

“The field of stem cell research and regenerative medicine has matured to the point where there are over 900 clinical trials worldwide. It is critical to develop a system of effective regulation of how these stem cell treatments are developed and manufactured so patients can benefit from future treatments.”

To address this challenge, CIRM has teamed up the International Alliance for Biological Standardization to host the 4th Cell Therapy Conference on Manufacturing and Testing of Pluripotent Stem Cells on June 5-6th in Los Angeles, California.

WHAT

The aim of this conference is twofold. Speakers will discuss how product development programs can be moved forward in a way that will meet regulatory requirements, so treatments can be approved.

The conference will also focus on key unresolved issues that need to be addressed for the manufacturing and safety testing of pluripotent stem cell-based therapies and then make recommendations to inform the future national and international policies. The overall aim is to provide participants with a road map so new treatments can achieve the highest regulatory standards and be made available to patients around the world.

The agenda of the conference will cover four main topics:

  1. Learning from the current pluripotent space and the development of international standards
  2. Bioanalytics and comparability of therapeutic stem cells
  3. Tumorigenicity testing for therapeutic safety
  4. Pluripotent stem cell manufacturing, storage, and shipment Issues

Using this “big tent” approach, speakers will exchange knowledge, experience and expertise to develop consensus recommendations around stem cell manufacturing and testing.  New data in this area will be introduced at the conference for the first time, such as a multi-center study to identify and optimize manufacturing-compatible methods for cell therapy safety.

WHO

The conference will bring together leading experts from industry, academia, health services and therapeutic regulatory bodies around the world, including the US Food and Drug Administration, European Medicines Agency, Japan Pharmaceuticals and Medical Devices Agency, and World Health Organization.

CIRM and IABS encourage individuals and organizations actively pursuing the development of stem cell therapies to attend.

WHY

robert deansIf you’re interested, but not quite sold on this conference, take the word of these experts:
Robert Deans, Chief Technology Officer at BlueRock Therapeutics:

“I believe standardization will be an increasingly crucial element in securing commercial success for regenerative cell therapies.  This applies to all facets of development, from cell characterization and patent protection through safety testing of final product.  Most important is the adherence of players in this sector to harmonized standards and creation of a scientifically credible market to the capital community.”

martin-pera-profileProfessor Martin Pera of the Jackson Laboratory, who directs the International  Stem Cell Initiative Genetics and Epigenetics Study Group:

“Participants at this meeting will survey and discuss the state of the art in the development of definitive assays for assessing the safety of pluripotent stem cell based therapies, a critical issue for the future of the field.  Anyone active in cell therapy should attend this meeting to contribute to a dialogue that will impact on research directions and ultimately help to define best practice in this sector.”

When and Where

The conference will be held in Los Angeles Airport Marriott on June 5-6th, 2018. Registration is now open on the IABS website and you can take advantage of discounted early bird registration before April 24th.

Breaking the isolation of rare diseases

Rare disease day

Rare Disease Day in Sacramento, California

How can something that affects 30 million Americans, one in ten people in the US, be called rare? But that’s the case with people who have a rare disease. There are around 7,000 different diseases that are categorized as rare because they affect fewer than 200,000 people. Less than five percent of these diseases have a treatment.

That’s why last Wednesday, in cities across the US, members of the rare disease community gathered to call for more support, more research, and more help for families battling these diseases. Their slogan tells their story, ‘Alone we are rare; Together we are strong.’

At the Rare Disease Day rally in Sacramento, California, I met Kerry Rivas. Kerry’s son Donovan has a life-threatening condition called Shprintzen-Goldberg Syndrome. Talk about rare. There are only 70 documented cases of the syndrome worldwide. Just getting a diagnosis for Donovan took years.

DonovanDonovan suffers from a lot of problems but the most serious affect his heart, lungs and spinal cord. Getting him the care he needs is time consuming and expensive and has forced Kerry and her family to make some big sacrifices. Even so they work hard to try and see that Donovan is able to lead as normal a life as is possible.

While the disease Kerry’s son has is rarer than most, everyone at Rare Disease Day had a similar story, and an equal commitment to doing all they can to be an effective advocate. And their voices are being heard.

To honor the occasion the US Food and Drug Administration (FDA) announced it was partnering with the National Organization of Rare Diseases (NORD) to hold listening sessions involving patients and FDA medical reviewers.

In a news release Peter L. Saltonstall, President and CEO of NORD, said:

“These listening sessions will provide FDA review division staff with better insight into what is important to patients in managing their diseases and improving their quality of life. It is important for FDA to understand, from the patient perspective, disease burden, management of symptoms, daily impact on quality of life, and patients’ risk tolerance. Patients and caregivers bring a pragmatic, realistic perspective about what they are willing to deal with in terms of potential risks and benefits for new therapies.”

FDA Commissioner Dr. Scott Gottlieb said his agency is committed to doing everything possible to help the rare disease community:

“Despite our successes, there are still no treatments for the vast proportion of rare diseases or conditions. FDA is committed to do what we can to stimulate the development of more products by improving the consistency and efficiency of our reviews, streamlining our processes and supporting rare disease research.”

At CIRM we are also committed to doing all we can to help the cause. Many of the diseases we are currently funding in clinical trials are rare diseases like ALS or Lou Gehrig’s disease, SCID, spinal cord injury and sickle cell disease.

Many pharmaceutical companies are shy about funding research targeting these diseases because the number of patients involved is small, so the chances of recouping their investment or even making a profit is small.

At CIRM we don’t have to worry about those considerations. Our focus is solely on helping those in need. People like Donovan Rivas.

Using the courts to protect patients from unapproved stem cell therapies

A recent article in Nature looked at using lawsuits to help rein in the activities of clinics offering “unapproved” therapies. CIRM’s Geoff Lomax explains.

Stem-Cell-Clinics-to-Trust

When public health officials wanted to raise awareness about the dangers of smoking they filed lawsuits against the tobacco companies. They accused Big Tobacco of deceptive marketing and hiding the negative health effects of smoking. Ultimately, they won. Now a new study says a similar tactic could prove effective in combating clinics that offer unproven stem cell therapies.

CIRM works tirelessly to accelerate the delivery of stem cell treatments to patients with unmet medical needs. But, that doesn’t mean we support any treatment that claims to help people. CIRM only partners with projects that have been given the go-ahead by the US Food and Drug Administration (FDA) to be tested in people in a clinical trial.  That’s because FDA approval means the clinical trial will be monitored and evaluated under high scientific and ethical standards.

In contrast, there are numerous examples where “stem-cell treatments” not sanctioned by the FDA are being marketed directly to patients. For years the FDA, CIRM and others have been warning consumers about the risks involved with these untested treatments. For example, just last  November the FDA issued a warning and advice for people considering stem cell treatments.

Legal steps

Last year CIRM also helped author a new California law designed to protect consumers. The law requires health care providers to disclose to patients when using a treatment that is not FDA approved or part of an FDA-sanctioned clinical trial.

At CIRM, we frequently direct patients seeking treatments to our Alpha Stem Cell Clinics Network. The Alpha Clinics only perform clinical trials that have been given the green light by the FDA, and they provide expert consultation and informed consent to patients to help ensure they make the best choice for themselves. Further, the Alpha Clinics follow up with patients after their treatments to evaluate safety and the effectiveness of the treatments.

These are steps that clinics offering unproven and unapproved therapies typically don’t follow. So, the question is how do you let people know about the risks involved in going to one of these clinics and how do you stop clinics offering “therapies” that might endanger the health of patients?

Using the law to hit clinics where it hurts

In a recently published perspective in the journal Nature an international team of policy experts considered whether civil lawsuits may play a role in stemming the tide of unproven treatments. In the article the authors say:

“The threat of financial liability for wrongdoing is the primary means by which civil law governs behavior in the private sector. Despite calls for stepping up enforcement efforts, the US Food and Drug Administration (FDA) is currently restricted in its ability to identify and target clinics operating in apparent violation of regulations. The fear of tort liability {lawsuits} may provide sufficient incentive for compliance and minimize the occurrence of unethical practices.”

The authors identified nine individual and class action lawsuits involving clinics offering what they called “unproven stem cell interventions.” A few of those were dismissed or decided in favor of the clinics, with judges saying the claims lacked merit. Most, however, were settled by the clinics with no ruling on the merits of the issue raised. Even without definitive judgements against the clinics the authors of the article conclude:

“Stem cell lawsuits could intensify publicity and raise awareness of the harms of unproven treatments, set legal precedent, reshape the media narrative from one focused on the right to try or practice to one highlighting the need for adequate safety and efficacy standards, and encourage authorities to turn their attention to policy reform and enforcement.”

The authors suggest the courts may provide a forum where medical experts can inform patients, the legal community and the public about good versus harmful clinical practices. In short, the authors believe the legal process can be an effective forum for to provide education and outreach to those with disease and the public at large.

The better option of course would be for the clinics themselves to reform their practices and engage with the FDA to test their therapies in a clinical trial. Until that happens the courts may offer an alternative approach to curbing the marketing of these unproven and unapproved therapies.

Creating a platform to help transplanted stem cells survive after a heart attack

heart

Developing new tools to repair damaged hearts

Repairing, even reversing, the damage caused by a heart attack is the Holy Grail of stem cell researchers. For years the Grail seemed out of reach because the cells that researchers transplanted into heart attack patients didn’t stick around long enough to do much good. Now researchers at Stanford may have found a way around that problem.

In a heart attack, a blockage cuts off the oxygen supply to muscle cells. Like any part of our body starved off oxygen the muscle cells start to die, and as they do the body responds by creating a layer of scars, effectively walling off the dead tissue from the surviving healthy tissue.  But that scar tissue makes it harder for the heart to effectively and efficiently pump blood around the body. That reduced blood flow has a big impact on a person’s ability to return to a normal life.

In the past, efforts to transplant stem cells into the heart had limited success. Researchers tried pairing the cells with factors called peptides to help boost their odds of surviving. That worked a little better but most of the peptides were also short-lived and weren’t able to make a big difference in the ability of transplanted cells to stick around long enough to help the heart heal.

Slow and steady approach

Now, in a CIRM-funded study published in the journal Nature Biomedical Engineering, a team at Stanford – led by Dr. Joseph Wu – believe they have managed to create a new way of delivering these cells, one that combines them with a slow-release delivery mechanism to increase their chances of success.

The team began by working with a subset of bone marrow cells that had been shown in previous studies to have what are called “pro-survival factors.” Then, working in mice, they identified three peptides that lived longer than other peptides. That was step one.

Step two involved creating a matrix, a kind of supporting scaffold, that would enable the researchers to link the three peptides and combine them with a delivery system they hoped would produce a slow release of pro-survival factors.

Step three was seeing if it worked. Using fluorescent markers, they were able to show, in laboratory tests, that unlinked peptides were rapidly released over two or three days. However, the linked peptides had a much slower release, lasting more than 15 days.

Out of the lab and into animals

While these petri dish experiments looked promising the big question was could this approach work in an animal model and, ultimately, in people. So, the team focused on cardiac progenitor cells (CPCs) which have shown potential to help repair damaged hearts, but which also have a low survival rate when transplanted into hearts that have experienced a heart attack.

The team delivered CPCs to the hearts of mice and found the cells without the pro-survival matrix didn’t last long – 80 percent of the cells were gone four days after they were injected, 90 percent were gone by day ten. In contrast the cells on the peptide-infused matrix were found in large numbers up to eight weeks after injection. And the cells didn’t just survive, they also engrafted and activated the heart’s own survival pathways.

Impact on heart

The team then tested to see if the treatment was helping improve heart function. They did echocardiograms and magnetic resonance imaging up to 8 weeks after the transplant surgery and found that the mice treated with the matrix combination had a statistically improved left ventricular function compared to the other mice.

Jayakumar Rajadas, one of the authors on the paper told CIRM that, because the matrix was partly made out of collagen, a substance the FDA has already approved for use in people, this could help in applying for approval to test it in people in the future:

“This paper is the first comprehensive report to demonstrate an FDA-compliant biomaterial to improve stem cell engraftment in the ischemic heart. Importantly, the biomaterial is collagen-based and can be readily tested in humans once regulatory approval is obtained.”

 

A year in review – CIRM’s 2017 Annual Report focuses on a year of accelerating stem cell treatments to patients

Facebook-AR-2017[3]

At CIRM we have our focus very clearly on the future, on accelerating stem cell therapies to patients with unmet medical needs. But every once in a while, it’s a good idea to look back at what you have already done. Knowing where you came from can help you get to where you are heading.

So, it’s with a sense of accomplishment that we are unveiling our 2017 Annual Report. It’s a look back at another banner year for the stem cell agency, the research we funded, the partnerships we created and, most importantly, the lives we touched.

It features profiles of several people who received stem cell therapies in CIRM-funded clinical trials and the impact those therapies are having on them. But it also looks at some of the other individuals who are such a vital part of the work we do: patient advocates, researchers and a member of our Grants Working Group which reviews applications for funding. Each one, in their own way, contributes to advancing the field.

The report also highlights some of the less obvious ways that our funding is benefitting California. For example, the additional $1.9 billion dollars our funding has helped generate through co-funding and partnerships, or the number of projects we are funding that have been awarded Regenerative Medicine Advanced Therapy Designation from the Food and Drug Administration (FDA), making them eligible for accelerated review if their results continue to be promising.

It’s a look back at a successful year.

But we are not resting on our laurels. We are already hard at work, determined to make 2018 even better.

 

 

Stories that caught our eye: How dying cells could help save lives; could modified blood stem cells reverse diabetes?; and FDA has good news for patients, bad news for rogue clinics

Gunsmoke

Growing up I loved watching old cowboy movies. Invariably the hero, even though mortally wounded, would manage to save the day and rescue the heroine and/or the town.

Now it seems some stem cells perform the same function, dying in order to save the lives of others.

Researchers at Kings College in London were trying to better understand Graft vs Host Disease (GvHD), a potentially fatal complication that can occur when a patient receives a blood stem cell transplant. In cases of GvHD, the transplanted donor cells turn on the patient and attack their healthy cells and tissues.

Some previous research had found that using bone marrow cells called mesenchymal stem cells (MSCs) had some success in combating GvHD. But it was unpredictable who it helped and why.

Working with mice, the Kings College team found that the MSCs were only effective if they died after being transplanted. It appears that it is only as they are dying that the MSCs engage with the individual’s immune system, telling it to stop attacking healthy tissues. The team also found that if they kill the MSCs just before transplanting them into mice, they were just as effective.

In a news article on HealthCanal, lead researcher Professor Francesco Dazzi, said the next step is to see if this will apply to, and help, people:

“The side effects of a stem cell transplant can be fatal and this factor is a serious consideration in deciding whether some people are suitable to undergo one. If we can be more confident that we can control these lethal complications in all patients, more people will be able to receive this life saving procedure. The next step will be to introduce clinical trials for patients with GvHD, either using the procedure only in patients with immune systems capable of killing mesenchymal stem cells, or killing these cells before they are infused into the patient, to see if this does indeed improve the success of treatment.”

The study is published in Science Translational Medicine.

Genetically modified blood stem cells reverse diabetes in mice (Todd Dubnicoff)

When functioning properly, the T cells of our immune system keep us healthy by detecting and killing off infected, damaged or cancerous cells in our body. But in the case of type 1 diabetes, a person’s own T cells turn against the body by mistakenly targeting and destroying perfectly normal islet cells in the pancreas, which are responsible for producing insulin. As a result, the insulin-dependent delivery of blood sugar to the energy-hungry organs is disrupted leading to many serious complications. Blood stem cell transplants have been performed to treat the disease by attempting to restart the immune system. The results have failed to provide a cure.

Now a new study, published in Science Translational Medicine, appears to explain why those previous attempts failed and how some genetic rejiggering could lead to a successful treatment for type 1 diabetes.

An analysis of the gene activity inside the blood stem cells of diabetic mice and humans reveals that these cells lack a protein called PD-L1. This protein is known to play an important role in putting the brakes on T cell activity. Because T cells are potent cell killers, it’s important for proteins like PD-L1 to keep the activated T cells in check.

Cell based image for t 1 diabetes

Credit: Andrea Panigada/Nancy Fliesler

Researchers from Boston Children’s Hospital hypothesized that adding back PD-L1 may prevent T cells from the indiscriminate killing of the body’s own insulin-producing cells. To test this idea, the research team genetically engineered mouse blood stem cells to produce the PD-L1 protein. Experiments with the cells in a petri dish showed that the addition of PD-L1 did indeed block the attack-on-self activity. And when these blood stem cells were transplanted into a diabetic mouse strain, the disease was reversed in most of the animals over the short term while a third of the mice had long-lasting benefits.

The researchers hope this targeting of PD-L1 production – which the researchers could also stimulate with pharmacological drugs – will contribute to a cure for type 1 diabetes.

FDA’s new guidelines for stem cell treatments

Gottlieb

FDA Commissioner Scott Gottlieb

Yesterday Scott Gottlieb, the Commissioner at the US Food and Drug Administration (FDA), laid out some new guidelines for the way the agency regulates stem cells and regenerative medicine. The news was good for patients, not so good for clinics offering unproven treatments.

First the good. Gottlieb announced new guidelines encouraging innovation in the development of stem cell therapies, and faster pathways for therapies, that show they are both safe and effective, to reach the patient.

At the same time, he detailed new rules that provide greater clarity about what clinics can do with stem cells without incurring the wrath of the FDA. Those guidelines detail the limits on the kinds of procedures clinics can offer and what ways they can “manipulate” those cells. Clinics that go beyond those limits could be in trouble.

In making the announcement Gottlieb said:

“To be clear, we remain committed to ensuring that patients have access to safe and effective regenerative medicine products as efficiently as possible. We are also committed to making sure we take action against products being unlawfully marketed that pose a potential significant risk to their safety. The framework we’re announcing today gives us the solid platform we need to continue to take enforcement action against a small number of clearly unscrupulous actors.”

Many of the details in the announcement match what CIRM has been pushing for some years. Randy Mills, our previous President and CEO, called for many of these changes in an Op Ed he co-wrote with former US Senator Bill Frist.

Our hope now is that the FDA continues to follow this promising path and turns these draft proposals into hard policy.

 

Progress to a Cure for Bubble Baby Disease

Welcome back to our “Throwback Thursday” series on the Stem Cellar. Over the years, we’ve accumulated an arsenal of exciting stem cell stories about advances towards stem cell-based cures for serious diseases. Today we’re featuring stories about the progress of CIRM-funded clinical trials for the treatment of a devastating, usually fatal, primary immune disease that strikes newborn babies.

evangelina in a bubble

Evie, a former “bubble baby” enjoying life by playing inside a giant plastic bubble

‘Bubble baby disease’ will one day be a thing of the past. That’s a bold statement, but I say it with confidence because of the recent advancements in stem cell gene therapies that are curing infants of this life-threatening immune disease.

The scientific name for ‘bubble baby disease’ is severe combined immunodeficiency (SCID). It prevents the proper development of important immune cells called B and T cells, leaving newborns without a functioning immune system. Because of this, SCID babies are highly susceptible to deadly infections, and without treatment, most of these babies do not live past their first year. Even a simple cold virus can be fatal.

Scientists are working hard to develop stem cell-based gene therapies that will cure SCID babies in their first months of life before they succumb to infections. The technology involves taking blood stem cells from a patient’s bone marrow and genetically correcting the SCID mutation in the DNA of these cells. The corrected stem cells are then transplanted back into the patient where they can grow and regenerate a healthy immune system. Early-stage clinical trials testing these stem cell gene therapies are showing very encouraging results. We’ll share a few of these stories with you below.

CIRM-funded trials for SCID

CIRM is funding three clinical trials, one from UCLA, one at Stanford and one from UCSF & St. Jude Children’s Research Hospital, that are treating different forms of SCID using stem cell gene therapies.

Adenosine Deaminase-Deficient SCID

The first trial is targeting a form of the disease called adenosine deaminase-deficient SCID or ADA-SCID. Patients with ADA-SCID are unable to make an enzyme that is essential for the function of infection-fighting immune cells called lymphocytes. Without working lymphocytes, infants eventually are diagnosed with SCID at 6 months. ADA-SCID occurs in approximately 1 in 200,000 newborns and makes up 15% of SCID cases.

CIRM is funding a Phase 2 trial for ADA-SCID that is testing a stem cell gene therapy called OTL-101 developed by Dr. Don Kohn and his team at UCLA and a company called Orchard Therapeutics. 10 patients were treated in the trial, and amazingly, nine of these patients were cured of their disease. The 10th patient was a teenager who received the treatment knowing that it might not work as it does in infants. You can read more about this trial in our blog from earlier this year.

In a recent news release, Orchard Therapeutics announced that the US Food and Drug Administration (FDA) has awarded Rare Pediatric Disease Designation to OTL-101, meaning that the company will qualify for priority review for drug approval by the FDA. You can read more about what this designation means in this blog.

X-linked SCID

The second SCID trial CIRM is funding is treating patients with X-linked SCID. These patients have a genetic mutation on a gene located on the X-chromosome that causes the disease. Because of this, the disease usually affects boys who have inherited the mutation from their mothers. X-linked SCID is the most common form of SCID and appears in 1 in 60,000 infants.

UCSF and St. Jude Children’s Research Hospital are conducting a Phase 1/2 trial for X-linked SCID. The trial, led by Dr. Brian Sorrentino, is transplanting a patient’s own genetically modified blood stem cells back into their body to give them a healthy new immune system. Patients do receive chemotherapy to remove their diseased bone marrow, but doctors at UCSF are optimizing low doses of chemotherapy for each patient to minimize any long-term effects. According to a UCSF news release, the trial is planning to treat 15 children over the next five years. Some of these patients have already been treated and we will likely get updates on their progress next year.

CIRM is also funding a third clinical trial out of Stanford University that is hoping to make bone marrow transplants safer for X-linked SCID patients. The team, led by Dr. Judy Shizuru, is developing a therapy that will remove unhealthy blood stem cells from SCID patients to improve the survival and engraftment of healthy bone marrow transplants. You can read more about this trial on our clinical trials page.

SCID Patients Cured by Stem Cells

These clinical trial results are definitely exciting, but what is more exciting are the patient stories that we have to share. We’ve spoken with a few of the families whose children participated in the UCLA and UCSF/St. Jude trials, and we asked them to share their stories so that other families can know that there is hope. They are truly inspiring stories of heartbreak and joyful celebration.

Evie is a now six-year-old girl who was diagnosed with ADA-SCID when she was just a few months old. She is now cured thanks to Don Kohn and the UCLA trial. Her mom gave a very moving presentation about Evie’s journey at the CIRM Bridges Trainee Annual Meeting this past July.  You can watch the 20-minute talk below:

Ronnie’s story

Ronnie SCID kid

Ronnie: Photo courtesy Pawash Priyank

Ronnie, who is still less than a year old, was diagnosed with X-linked SCID just days after he was born. Luckily doctors told his parents about the UCSF/St. Jude trial and Ronnie was given the life-saving stem cell gene therapy before he was six months old. Now Ronnie is building a healthy immune system and is doing well back at home with his family. Ronnie’s dad Pawash shared his families moving story at our September Board meeting and you can watch it here.

Our mission at CIRM is to accelerate stem cell treatments to patients with unmet medical needs. We hope that by funding promising clinical trials like the ones mentioned in this blog, that one day soon there will be approved stem cell therapies for patients with SCID and other life-threatening diseases.

Using heart stem cells to help boys battling a deadly disorder

 

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Caleb Sizemore, a young man with DMD, speaks to the CIRM Board about his treatment in the Capricor clinical trial.

It’s hard to imagine how missing just one tiny protein can have such a devastating impact on a person. But with Duchenne Muscular Dystrophy (DMD) the lack of a single protein called dystrophin has deadly consequences. Now a new study is offering hope we may be able to help people with this rare genetic disorder.

DMD is a muscle wasting condition that steadily destroys the muscles in the arms and legs, heart and respiratory system. It affects mostly boys and it starts early in life, sometimes as young as 3 years old, and never lets up. By early teens many boys are unable to walk and are in a wheelchair. Their heart and breathing are also affected. In the past most people with DMD didn’t survive their teens. Now it’s more common for them to live into their 20’s and 30’s, but not much beyond that.

Results from a clinical trial being run by Capricor Therapeutics – and funded by CIRM – suggest we may be able to halt, and even reverse, some of the impacts of DMD.

Capricor has developed a therapy called CAP-1002 using cells derived from heart stem cells, called cardiospheres. Boys and young men with DMD who were treated with CAP-1002 experienced what Capricor calls “significant and sustained improvements in cardiac structure and function, as well as skeletal muscle function.”

In a news release Dr. Ronald Victor, a researcher at Cedars-Sinai Heart Institute and the lead investigator for the trial, said they followed these patients for 12 months after treatment and the results are encouraging:

“Because Duchenne muscular dystrophy is a devastating, muscle-wasting disease that causes physical debilitation and eventually heart failure, the improvements in heart and skeletal muscle in those treated with a single dose of CAP-1002 are very promising and show that a subsequent trial is warranted. These early results provide hope for the Duchenne community, which is in urgent need of a major therapeutic breakthrough.”

According to the 12-month results:

  • 89 percent of patients treated with CAP-1002 showed sustained or improved muscle function compared to untreated patients
  • The CAP-1002 group had improved heart muscle function compared to the untreated group
  • The CAP-1002 group had reduced scarring on their heart compared to the untreated group.

Now, these results are still very early stage and there’s a danger in reading too much into them. However, the fact that they are sustained over one year is a promising sign. Also, none of the treated patients experienced any serious side effects from the therapy.

The team at Capricor now plans to go back to the US Food and Drug Administration (FDA) to get clearance to launch an even larger study in 2018.

For a condition like DMD, that has no cure and where treatments can simply slow down the progression of the disorder, this is a hopeful start.

Caleb Sizemore is one of the people treated in this trial. You can read his story and listen to him describing the impact of the treatment on his life.

Turning the corner with the FDA and NIH; CIRM creates new collaborations to advance stem cell research

FDAThis blog is part of the Month of CIRM series on the Stem Cellar

A lot can change in a couple of years. Just take our relationship with the US Food and Drug Administration (FDA).

When we were putting together our Strategic Plan in 2015 we did a survey of key players and stakeholders at CIRM – Board members, researchers, patient advocates etc. – and a whopping 70 percent of them listed the FDA as the biggest impediment for the development of stem cell treatments.

As one stakeholder told us at the time:

“Is perfect becoming the enemy of better? One recent treatment touted by the FDA as a regulatory success had such a high clinical development hurdle placed on it that by the time it was finally approved the standard of care had evolved. When it was finally approved, five years later, its market potential had significantly eroded and the product failed commercially.”

Changing the conversation

To overcome these hurdles we set a goal of changing the regulatory landscape, finding a way to make the system faster and more efficient, but without reducing the emphasis on the safety of patients. One of the ways we did this was by launching our “Stem Cell Champions” campaign to engage patients, patient advocates, the public and everyone else who supports stem cell research to press for change at the FDA. We also worked with other organizations to help get the 21st Century Cures Act passed.

21 century cures

Today the regulatory landscape looks quite different than it did just a few years ago. Thanks to the 21st Century Cures Act the FDA has created expedited pathways for stem cell therapies that show promise. One of those is called the Regenerative Medicine Advanced Therapy (RMAT) designation, which gives projects that show they are both safe and effective in early-stage clinical trials the possibility of an accelerated review by the FDA. Of the first projects given RMAT designation, three were CIRM-funded projects (Humacyte, jCyte and Asterias)

Partnering with the NIH

Our work has also paved the way for a closer relationship with the National Institutes of Health (NIH), which is looking at CIRM as a model for advancing the field of regenerative medicine.

In recent years we have created a number of innovations including introducing CIRM 2.0, which dramatically improved our ability to fund the most promising research, making it faster, easier and more predictable for researchers to apply. We also created the Stem Cell Center  to make it easier to move the most promising research out of the lab and into clinical trials, and to give researchers the support they need to help make those trials successful. To address the need for high-quality stem cell clinical trials we created the CIRM Alpha Stem Cell Clinic Network. This is a network of leading medical centers around the state that specialize in delivering stem cell therapies, sharing best practices and creating new ways of making it as easy as possible for patients to get the care they need.

The NIH looked at these innovations and liked them. So much so they invited CIRM to come to Washington DC and talk about them. It was a great opportunity so, of course, we said yes. We expected them to carve out a few hours for us to chat. Instead they blocked out a day and a half and brought in the heads of their different divisions to hear what we had to say.

A model for the future

We hope the meeting is, to paraphrase Humphrey Bogart at the end of Casablanca, “the start of a beautiful friendship.” We are already seeing signs that it’s not just a passing whim. In July the NIH held a workshop that focused on what will it take to make genome editing technologies, like CRISPR, a clinical reality. Francis Collins, NIH Director, invited CIRM to be part of the workshop that included thought leaders from academia, industry and patients advocates. The workshop ended with a recommendation that the NIH should consider building a center of excellence in gene editing and transplantation, based on the CIRM model (my emphasis).  This would bring together a multidisciplinary disease team including, process development, cGMP manufacturing, regulatory and clinical development for Investigational New Drug (IND) filing and conducting clinical trials, all under one roof.

dr_collins

Dr. Francis Collins, Director of the NIH

In preparation, the NIH visited the CIRM-funded Stem Cell Center at the City of Hope to explore ways to develop this collaboration. And the NIH has already begun implementing these suggestions starting with a treatment targeting sickle cell disease.

There are no guarantees in science. But we know that if you spend all your time banging your head against a door all you get is a headache. Today it feels like the FDA has opened the door and that, together with the NIH, they are more open to collaborating with organizations like CIRM. We have removed the headache, and created the possibility that by working together we truly can accelerate stem cell research and deliver the therapies that so many patients desperately need.