Medeor Therapeutics Completes Enrollment in CIRM-Funded Clinical Trial for Kidney Transplant Patients

A CIRM-funded clinical trial to help kidney transplant patients avoid the need for anti-rejection or immunosuppressive medications has completed enrollment and transplantation of all patients.

Medeor Therapeutics’ MDR-101 Phase 3 multi-center clinical trial involved 30 patients; 20 of them were treated with MDR-101, and 10 control subjects were given standard care. CIRM awarded Medeor, based in South San Francisco, $18.8 million for this research in January 2018.

More than 650,000 Americans suffer from end-stage kidney disease – a life-threatening condition caused by the loss of kidney function. For these people the best treatment option is a kidney transplant from a genetically matched, living donor. Even matched patients, however, face a lifetime on immunosuppressive drugs to prevent their immune system from rejecting the transplanted organ. These drugs can be effective at preventing rejection, but they come at a cost. Because they are toxic these medications increase a transplant patient’s life-time risk of cancer, diabetes, heart disease and infections.

Medeor Therapeutics developed its MDR-101 therapy to reprogram the patient’s immune system to accept a transplanted kidney without the need for long term use of immunosuppression drugs.

The company takes peripheral blood stem cells from the organ donor and infuses them into the patient receiving the donor’s kidney. This creates a condition called “mixed chimerism” where immune cells from the donor help the patient’s immune system adapt to and tolerate the donor’s kidney. 

After a standard kidney transplant, the patient is given a combination of three anti-rejection medications which they typically have to remain on for the rest of their lives. However, the Medeor patients, by day 40 post-transplant, are only taking one medication and the hope is that immunosuppression is discontinued at the end of one year.

“Chronic kidney disease and kidney failure are a growing problem in the US, that’s why it’s so important that we find new ways to reduce the burden on patients and increase the odds of a successful transplant with long term benefit,” says Maria T. Millan, M.D., President and CEO of CIRM. “Medeor’s approach may not only reduce the likelihood of a patient’s body rejecting the transplanted organ, but it can also improve the quality of life for these people and reduce overall health care costs by eliminating the need to stay on these immunosuppressive medications for life.”

In an earlier Phase 2 trial, a majority of patients achieved mixed chimerism. Approximately 74 percent of those patients have been off all immunosuppressive drugs for more than two years, including some who continue to be off immunosuppressive medications 15 years after their surgery.

“Today’s news is a tremendous milestone not only for Medeor but for the entire transplant community. This is the first randomized, multi-center pivotal study designed specifically to stop the use of all immunosuppressive anti-rejection drugs post-transplant. This therapy can be a true game changer in our efforts to transform transplant outcomes and help patients live healthier lives,” said Dan Brennan, MD, Chief Medical Officer at Medeor Therapeutics.

If the results from this pivotal clinical trial show that MDR-101 is both safe and effective, Medeor may apply to the Food and Drug Administration (FDA) for approval to market their approach to other patients in the U.S.

CIRM-funded kidney transplant procedure eyeing faster approval

Kidney transplant surgery.

Medeor Therapeutics, which is running a CIRM-funded clinical trial to help people getting kidney transplants, just got some really good news. The US Food and Drug Administration (FDA) has just granted their product Regenerative Medicine Advanced Therapy (RMAT) designation. That’s a big deal because it means they may be able to apply for faster review and approval and get their therapy to more patients faster.

Here’s why that RMAT designation matters.

Over 650,000 Americans suffer from end-stage kidney disease – a life-threatening condition caused by the loss of kidney function. The best available treatment for these patients is a kidney transplant from a genetically matched living donor. However, patients who receive a transplant must take life-long immunosuppressive drugs to prevent their immune system from rejecting the transplanted organ. Over time, these drugs are toxic and can increase a patient’s risk of infection, heart disease, cancer and diabetes.  Despite these drugs, many patients still lose transplanted organs due to rejection.

To tackle this problem Medeor is developing a stem cell-based therapy called MDR-101. This is being tested in a Phase 3 clinical trial and it’s hoped it will eliminate the need for immunosuppressive drugs in genetically matched kidney transplant patients.

The company takes blood-forming stem cells and immune cells from the organ donor and infuses them into the patient receiving the donor’s kidney. Introducing the donor’s immune cells into the patient creates a condition called “mixed chimerism” where immune cells from the patient and the donor are able to co-exist. In this way, the patient’s immune system is able to adapt to and tolerate the donor’s kidney, potentially eliminating the need for the immunosuppressive drugs that are normally necessary to prevent transplant rejection.

So how does getting RMAT designation help that? Well, the FDA created the RMAT program to help speed up the development and review of regenerative medicine therapies that can treat, modify, reverse, or cure a serious condition. If MDR-101shows it is both safe and effective RMAT could help it get faster approval for wider use.

In a news release Giovanni Ferrara, President and CEO of Medeor, welcomed the news.

“This important designation underscores the tremendous unmet medical need for alternatives to today’s immunosuppressive therapies for transplantation. We have the potential to help people live longer, healthier lives without the need for high dose and chronic immunosuppression and we thank the FDA for this designation that will assist us progressing as efficiently as possible toward a commercially available product.”

This is the seventh CIRM-supported project that has been granted RMAT designation. The others are jCyte, Lineage, Humacyte, St. Jude’s/UCSF X-linked SCID, Poseida, Capricor

Two rare diseases, two pieces of good news

Dr. Stephanie Cherqui

Last week saw a flurry of really encouraging reports from projects that CIRM has supported. We blogged about two of them last Wednesday, but here’s another two programs showing promising results.

UC San Diego researcher Dr. Stephanie Cherqui is running a CIRM-funded clinical trial for cystinosis. This is a condition where patients lack the ability to clear an amino acid called cystine from their cells. As the cystine builds up it can lead to multi-organ failure affecting the kidneys, eyes, thyroid, muscle, and pancreas.

Dr. Cherqui uses the patient’s own blood stem cells, that have been genetically corrected in the lab to remove the defective gene that causes the problem. It’s hoped these new cells will help reduce the cystine buildup.

The data presented at the annual meeting of the American Society of Cell and Gene Therapy (ASCGT) focused on the first patient treated with this approach. Six months after being treated the patient is showing positive trends in kidney function. His glomerular filtration rate (a measure of how well the kidneys are working) has risen from 38 (considered a sign of moderate to severe loss of kidney function) to 52 (mild loss of kidney function). In addition, he has not had to take the medication he previously needed to control the disorder, nor has he experienced any serious side effects from the therapy.

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Dr. Linda Marban of Capricor

Capricor Therapeutics also had some positive news about its therapy for people with Duchenne’s Muscular Dystrophy (DMD). This is a progressive genetic disorder that slowly destroys the muscles. It affects mostly boys. By their teens many are unable to walk, and most die of heart or lung failure in their 20’s. 

Capricor is using a therapy called CAP-1002, using cells derived from heart stem cells, in the HOPE-2 clinical trial.

In a news release Capricor said 12-month data from the trial showed improvements in heart function, lung function and upper body strength. In contrast, a placebo control group that didn’t get the CAP-1002 treatment saw their condition deteriorate.

Craig McDonald, M.D., the lead investigator on the study, says these results are really encouraging.  “I am incredibly pleased with the outcome of the HOPE-2 trial which demonstrated clinically relevant benefits of CAP-1002 which resulted in measurable improvements in upper limb, cardiac and respiratory function. This is the first clinical trial which shows benefit to patients in advanced stages of DMD for which treatment options are limited.”

You can read the story of Caleb Sizemore, one of the patients treated in the CIRM-funded portion of this trial.

Huge honor, hugely deserved for CIRM-funded stem cell researcher

Dr. Andy McMahon: Photo courtesy USC

Andy McMahon is one of the most understated, humble and low-key people you are ever likely to meet. He’s also one of the smartest. And he has a collection of titles to prove it. He is the W.M. Keck Provost and University Professor in USC’s departments of Stem Cell Biology and Regenerative Medicine at the Keck School of Medicine, and Biological Sciences at the Dornsife College of Letters, Arts and Sciences, a fellow of the American Association for the Advancement of Science, the American Academy of Arts and Sciences, the European Molecular Biology Organization, and the Royal Society.

Now you can add to that list that Andy is a member of the National Academy of Sciences (NAS). Election to the NAS is no ordinary honor. It’s one of the highest in the scientific world.

In a USC news release Dean Laura Mosqueda from the Keck School praised Andy saying: “We’re delighted that Dr. McMahon is being recognized as a newly elected member of the National Academy of Sciences. Because new members are elected by current members, this represents recognition of Dr. McMahon’s achievements by his most esteemed peers in all scientific fields.”

Not surprisingly CIRM has funded some of Andy’s work – well, we do pride ourselves on working with the best and brightest scientists – and that research is taking on added importance with the spread of COVID-19. Andy’s area of specialty is kidneys, trying to develop new ways to repair damaged or injured kidneys. Recent studies show that between 3 and 9 percent of patients with COVID-19 develop an acute kidney injury; in effect their kidneys suddenly stop working and many of these patients have to undergo dialysis to stay alive.

Even those who recover are at increased risk for developing more chronic, even end-stage kidney disease. That’s where Andy’s work could prove most useful. His team are using human stem cells to create mini artificial kidneys that have many of the same properties as the real thing. These so-called “organoids” enable us to study chronic kidney disease, come up with ideas to repair damage or slow down the progression of the disease, even help improve the chances of a successful transplant if that becomes necessary.

You can hear Andy talk about his work here:

CIRM is now funding a number of projects targeting COVID-19, including a clinical trial using convalescent plasma gel, and intends investing in more in the coming weeks and months. You can read about that here.

We are also funding several clinical trials targeting kidney failure. You can read about those on our Clinical Trials Dashboard page – diseases are listed alphabetically.

The Most Important Gift of All

Photo courtesy American Hospital Association

There are many players who have a key role in helping make a stem cell therapy work. The scientists who develop the therapy, the medical team who deliver it and funders like CIRM who provide the money to make this all happen. But vital as they are, in some therapies there is another, even more important group; the people who donate life-saving organs and tissues for transplant and research.

Organ and tissue donation saves lives, increases knowledge of diseases, and allow for the development of novel medications to treat them. When individuals or their families authorize donation for transplant or medical research, they allow their loved ones to build a long-lasting legacy of hope that could not be accomplished in any other way.

Four of CIRM’s clinical trials involve organ donations – three kidney transplant programs (you can read about those here, here and here) and one targeting type 1 diabetes.

Dr. Nikole Neidlinger, the Chief Medical Officer with Donor Network West – the federally designated organ and tissue recovery organization for Northern California and Nevada – says it is important to recognize the critical contribution made in a time of grief and crisis by the families of deceased donors. 

“For many families who donate, a loved one has died, and they are in shock. Even so, they are willing to say yes to giving others a second chance at life and to help others to advance science. Without them, none of this would be possible. It’s the ultimate act of generosity and compassion.”

The latest CIRM-funded clinical trial involving donated tissue is with Dr. Peter Stock and his team at UCSF. They are working on a treatment for type 1 diabetes (T1D), where the body’s immune system destroys its own pancreatic beta cells. These cells are necessary to produce insulin, which regulates blood sugar levels in the body.

In the past people have tried transplanting beta cells, from donated pancreatic islets, into patients with type 1 diabetes to try and reverse the course of the disease. However, this requires islets from multiple donors and the shortage of organ and tissue donors makes this difficult to do.

Dr. Stock’s clinical trial at UCSF aims to address these limitations.  He is going to transplant both pancreatic islets and parathyroid glands, from the same donor, into T1 patients. It’s hoped this combination approach will increase beta cell survival, potentially boosting long-term insulin production and removing the need for multiple donors.  And because the transplant is placed in the patient’s forearm, it makes it easier to monitor the effectiveness and accessibility of the islet transplants. Of equal importance, the development of this site will facilitate the transplantation of stem cell derived beta cells, which are very close to clinical application.

“As a transplant surgeon, it is an absolute privilege to be able to witness the life-saving organ transplants made possible by the selfless generosity of the donor families. It is hard to imagine how families have the will to think about helping others at a time of their greatest grief. It is this willingness to help others that restores my faith in humanity”

Donor Network West plays a vital role in this process. In 2018 alone, the organization recovered 702 donor samples for research. Thanks to the generosity of the donors/donor families, the donor network has been able to provide parathyroid and pancreas tissue essential to make this clinical trial a success”

“One organ donor can save the lives of up to eight people and a tissue donor can heal more than 75 others,” says Dr. Neidlinger. “For families, the knowledge that they are transforming someone’s life, and possibly preventing another family from experiencing this same loss, can serve as a silver lining during their time of sorrow. .”

Organs that can be donated

Kidney (x2), Heart, Lungs (x2), Liver, Pancreas, Intestine

Tissue that can be donated

Corneas, Heart valves, Skin, Bone, Tendons, Cartilage, Veins

Currently, there are over 113,000 people in the U.S. waiting for an organ transplant, of which 84 % are in need of kidneys.  Sadly, 22 people die every day waiting for an organ transplant that does not come in time. The prospect of an effective treatment for type 1 diabetes means hope for thousands of people living with the chronic condition.

Rare Disease Gets Big Boost from California’s Stem Cell Agency

UC Irvine’s Dr. Leslie Thompson and patient advocate Frances Saldana after the CIRM Board vote to approve funding for Huntington’s disease

If you were looking for a poster child for an unmet medical need Huntington’s disease (HD) would be high on the list. It’s a devastating disease that attacks the brain, steadily destroying the ability to control body movement and speech. It impairs thinking and often leads to dementia. It’s always fatal and there are no treatments that can stop or reverse the course of the disease. Today the Board of the California Institute for Regenerative Medicine (CIRM) voted to support a project that shows promise in changing that.

The Board voted to approve $6 million to enable Dr. Leslie Thompson and her team at the University of California, Irvine to do the late stage testing needed to apply to the US Food and Drug Administration for permission to start a clinical trial in people. The therapy involves transplanting stem cells that have been turned into neural stem cells which secrete a molecule called brain-derived neurotrophic factor (BDNF), which has been shown to promote the growth and improve the function of brain cells. The goal is to slow down the progression of this debilitating disease.

“Huntington’s disease affects around 30,000 people in the US and children born to parents with HD have a 50/50 chance of getting the disease themselves,” says Dr. Maria T. Millan, the President and CEO of CIRM. “We have supported Dr. Thompson’s work for a number of years, reflecting our commitment to helping the best science advance, and are hopeful today’s vote will take it a crucial step closer to a clinical trial.”

Another project supported by CIRM at an earlier stage of research was also given funding for a clinical trial.

The Board approved almost $12 million to support a clinical trial to help people undergoing a kidney transplant. Right now, there are around 100,000 people in the US waiting to get a kidney transplant. Even those fortunate enough to get one face a lifetime on immunosuppressive drugs to stop the body rejecting the new organ, drugs that increase the risk for infection, heart disease and diabetes.  

Dr. Everett Meyer, and his team at Stanford University, will use a combination of healthy donor stem cells and the patient’s own regulatory T cells (Tregs), to train the patient’s immune system to accept the transplanted kidney and eliminate the need for immunosuppressive drugs.

The initial group targeted in this clinical trial are people with what are called HLA-mismatched kidneys. This is where the donor and recipient do not share the same human leukocyte antigens (HLAs), proteins located on the surface of immune cells and other cells in the body. Around 50 percent of patients with HLA-mismatched transplants experience rejection of the organ.

In his application Dr. Meyer said they have a simple goal: “The goal is “one kidney for life” off drugs with safety for all patients. The overall health status of patients off immunosuppressive drugs will improve due to reduction in side effects associated with these drugs, and due to reduced graft loss afforded by tolerance induction that will prevent chronic rejection.”

The most popular Stem Cellar posts of 2018

The blog

You never know when you write something if people are going to read it. Sometimes you wonder if anyone is going to read it. So, it’s always fun, and educational, to look back at the end of the year and see which pieces got the most eyeballs.

It isn’t always the ones you think will draw the biggest audiences. Sometimes it is diseases that are considered “rare” (those affecting fewer than 200,000 people) that get the most attention.

Maybe it’s because those diseases have such a powerful online community which shares news, any news, about their condition of interest with everyone they know. Whatever the reason, we are always delighted to share encouraging news about research we are funding or encouraging research that someone else is funding.

That was certainly the case with the top two stories this year. Both were related to ALS or Lou Gehrig’s disease.  It’s a particularly nasty condition. People diagnosed with ALS have a life expectancy of just 2 to 5 years. So it’s probably not a big surprise that stories suggesting stem cells could expand that life span got a big reception.

Whatever the reason, we’re just happy to share hopeful news with everyone who comes to our blog.

And so, without further ado, here is the list of the most popular Stem Cellar Blog Posts for 2018.

All of us in the Communications team at CIRM consider it an honor and privilege to be able to work here and to meet many of the people behind these stories; the researchers and the patients and patient advocates. They are an extraordinary group of individuals who help remind us why we do this work and why it is important. We love our work and we hope you enjoy it too. We plan to be every bit as active and engaged in 2019.

CIRM-funded medical research and development company does $150M deal to improve care for dialysis patients

Fresenius & Humacyte

Nearly half a million Americans with kidney disease are on dialysis, so it’s not surprising the CIRM Board had no hesitation, back in July 2016, in funding a program to make it easier and safer to get that life-saving therapy.

That’s why it’s gratifying to now hear that Humacyte, the company behind this new dialysis device, has just signed a $150 million deal with Fresenius Medical Care, to make their product more widely available.

The CIRM Board gave Humacyte $10 million for a Phase 3 clinical trial to test a bioengineered vein needed by people undergoing hemodialysis, the most common form of dialysis.

Humacyte HAV

The vein – called a human acellular vessel or HAV – is implanted in the arm and used to carry the patient’s blood to and from an artificial kidney that removes waste from the blood. Current synthetic versions of this device have many problems, including clotting, infections and rejection. In tests, Humacyte’s HAV has fewer complications. In addition, over time the patient’s own stem cells start to populate the bioengineered vein, in effect making it part of the patient’s own body.

Fresenius Medical Care is investing $150 million in Humacyte, with a plan to use the device in its dialysis clinics worldwide. As an indication of how highly they value the device, the deal grants Fresenius a 19% ownership stake in the company.

In an interview with FierceBiotech, Jeff Lawson, Humacyte’s Chief Medical Officer, said if all goes well the company plans to file for Food and Drug Administration (FDA) approval in 2019 and hopes it will be widely available in 2020.

In addition to being used for kidney disease the device is also being tested for peripheral artery disease, vascular trauma and other cardiovascular indications. Lawson says testing the device first in kidney disease will provide a solid proving ground for it.

“It’s a very safe place to develop new vascular technologies under clinical study. From a regulatory safety standpoint, this is the first area we could enter safely and work with the FDA to get approval for a complete new technology.”

This is another example of what we call CIRM’s “value proposition”; the fact that we don’t just provide funding, we also provide support on many other levels and that has a whole range of benefits. When our Grants Working Group – the independent panel of experts who review our scientific applications – and the CIRM Board approves a project it’s like giving it the CIRM Good Housekeeping Seal of Approval. That doesn’t just help that particular project, it can help attract further investment in the company behind it, enabling it to expand operations and create jobs and ultimately, we hope, help advance the field as a whole.

Those benefits are substantial. To date we have been able to use our funding to leverage around $2 billion in additional dollars in terms of outside companies investing in companies like Humacyte, or researchers using data from research we funded to get additional funding from agencies like the National Institutes of Health.

So, when a company like Humacyte is the object of such a lucrative agreement it’s not just a compliment to the quality of the work they do, it’s also a reflection of our ability to pick great projects.

Stem cell study holds out promise for kidney disease

Kidney failure

Image via youtube.com

Kidney failure is the Rodney Dangerfield of diseases, it really doesn’t get the respect it deserves. An estimated 660,000 Americans suffer from kidney failure and around 47,000 people die from it every year. That’s more than die from breast or prostate cancer. But now a new study has identified a promising stem cell candidate that could help in finding a way to help repair damaged kidneys.

Kidneys are the body’s waste disposal system, filtering our blood and cleaning out all the waste products. Our kidneys have a limited ability to help repair themselves but if someone suffers from chronic kidney disease then their kidneys are slowly overwhelmed and that leads to end stage renal disease. At that point the patient’s options are limited to dialysis or an organ transplant.

Survivors hold out hope

Italian researchers had identified some cells in the kidneys that showed a regenerative ability. These cells, which were characterized by the expression of a molecule called CD133, were able to survive injury and create different types of kidney cells.

Researchers at the University of Torino in Italy decided to take these findings further and explore precisely how CD133 worked and if they could take advantage of that and use it to help repair damaged kidneys.

In their findings, published in the journal Stem Cells Translational Medicine, the researchers began by working with a chemotherapy drug called cisplatin, which is used against a broad range of cancers but is also known to cause damage to kidneys in around one third of all patients. The team found that CD133 was an important factor in helping those damaged kidneys recover. They also found that CD133 prevents aging of kidney progenitor cells, the kind of cell needed to help create new cells to repair the kidneys in future.

Hope for further research

The finding opens up a number of possible lines of research, including exploring whether infusions of CD133 could help patients whose kidneys are no longer able to produce enough of the molecule to help repair damage.

In an interview in DD News, Dr. Anthony Atala, Director of the Wake Forest Institute for Regenerative Medicine – praised the research:

“This is an interesting and novel finding. Because the work identifies mechanisms potentially involved in the repair of tissue after injury, it suggests the possibility of new therapies for tissue repair and regeneration.”

CIRM is funding several projects targeting kidney disease including four clinical trials for kidney failure. These are all late-stage kidney failure problems so if the CD133 research lives up to its promise it might be able to help people at an earlier stage of disease.

CIRM-Funded Clinical Trials Targeting the Heart, Pancreas, and Kidneys

This blog is part of our Month of CIRM series, which features our Agency’s progress towards achieving our mission to accelerate stem cell treatments to patients with unmet medical needs.

This week, we’re highlighting CIRM-funded clinical trials to address the growing interest in our rapidly expanding clinical portfolio. Today we are featuring trials in our organ systems portfolio, specifically focusing on diseases of the heart/vasculature system, the pancreas and the kidneys.

CIRM has funded a total of nine trials targeting these disease areas, and eight of these trials are currently active. Check out the infographic below for a list of our currently active trials.

For more details about all CIRM-funded clinical trials, visit our clinical trials page and read our clinical trials brochure which provides brief overviews of each trial.