Stem cell therapy for deadly childhood immune disorder goes four for four

The gold standard for any new therapy in the U.S. is approval by the Food and Drug Administration (FDA). This approval clears the therapy for sale and often also means it will be covered by insurance. But along the way there are other designations that can mean a lot to a company developing a new approach to a deadly disease.

That’s what recently happened with Mustang Bio’s MB-107. The therapy was given Orphan Drug Designation for the treatment of X-linked Severe Combined Immunodeficiency (SCID) also known as “bubble baby disease”, a rare but deadly immune disorder affecting children. This is the same therapy that CIRM is funding in a clinical trial we’ve blogged about in the past.  

Getting Orphan Drug Designation can be a big deal. It is given to therapies intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S. It comes with some sweet incentives, such as tax credits toward the cost of clinical trials and prescription drug user fee waivers. And, if the product becomes the first in its class to get FDA approval for a particular disease, it is entitled to seven years of market exclusivity, which is independent from intellectual property protection.

This is not the first time Mustang Bio’s MB-107 has been acknowledged as a potential gamechanger. It’s also been given three other classifications both here in the US and in Europe.

  • Rare Pediatric Disease Designation: this also applies to treatments for diseases affecting fewer than 200,000 people in the US that have the potential to provide clinically meaningful benefits to patients. It provides the company with a “voucher” that they can use to apply for priority review for another therapy they are developing. The hope is that this will encourage companies to develop treatments for rare childhood diseases that might not otherwise be profitable.
  • Regenerative Medicine Advanced Therapy (RMAT) designation: this allows for faster, more streamlined approvals of regenerative medicine products
  • Advanced Therapy Medicinal Product classification: this is granted by the European Medicines Agency (EMA) to medicines that are based on genes, tissues or cells and can offer groundbreaking opportunities for the treatment of disease.

Of course, none of these designations are a guarantee that Mustang Bio’s MB-107 will ultimately get FDA approval, but they’re a pretty good indication that a lot of people have confidence they’ll get there.

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 CIRM supported studies highlighted in Nature as promising approaches for blood disorders

Blood stem cells (blue) are cleared from the bone marrow (purple) before new stem cells can be transplanted.Credit: Dennis Kunkel Microscopy/SPL

Problems with blood stem cells, a type of stem cell in your bone marrow that gives rise to various kinds of blood cells, can sometimes result in blood cancer as well as genetic and autoimmune diseases.

It is because of this that researchers have looked towards blood stem cell transplants, which involves replacing a person’s defective blood stem cells with healthy ones take from either a donor or the patient themselves.

However, before this can be done, the existing population of defective stem cells must be eradicated in order to allow the transplanted blood stem cells to properly anchor themselves into the bone marrow. Current options for this include full-body radiation or chemotherapy, but these approaches are extremely toxic.

But what if there was a way to selectively target these blood stem cells in order to make the transplants much safer?

An article published in Nature highlights the advancements made in the field of blood stem cell transplantation, some of which is work that is funded by yours truly.

One of the approaches highlighted involves the work that we funded related to Forty Seven and an antibody created that inhibits a protein called CD47.

The article discusses how Forty Seven tested two antibodies in monkeys. One antibody blocks the activity of a molecule called c-Kit, which is found on blood stem cells. The other is the antibody that blocks CD47, which is found on some immune cells. Inhibiting CD47 allows those immune cells to sweep up the stem cells that were targeted by the c-Kit antibody, thereby boosting its effectiveness. In early tests, the two antibodies used together reduced the number of blood stem cells in bone marrow. The next step for this team is to demonstrate that the treatment clears out the old supply of stem cells well enough to allow transplanted cells to flourish.

You can read more about the CD47 antibody in a previous blog post.

Another notable segment of this article is the CIRM funded trial that is being conducted by Dr. Judith Shizuru at Stanford University. This clinical trial also uses an antibody that targets c-Kit found on blood stem cells.

The purpose of this trial is to wipe out the problematic blood stem cells in infants with X-linked Severe combined immunodeficiency (SCID), a rare fatal genetic disorder that leaves infants without a functional immune system, in order to introduce properly functioning blood stem cells. Dr. Shizuru and her team found that transplanted blood stem cells, in this case from donors who did not have the disease, successfully took hold in the bone marrow of four out of six of the babies.

You can read more about Dr. Shizuru’s work in a previous blog post as well.

CIRM-funded therapy helps “bubble babies” lead a normal life

Ja’Ceon Golden; ‘cured” of SCID

At CIRM we are very cautious about using the “c” word. Saying someone has been “cured” is a powerful statement but one that loses its meaning when over used or used inappropriately. However, in the case of a new study from U.C. San Francisco and St. Jude Children’s Research Hospital in Memphis, saying “cure” is not just accurate, it’s a celebration of something that would have seemed impossible just a few years ago.

The research focuses on children with a specific form of Severe Combined Immunodeficiency (SCID) called X-Linked SCID. It’s also known as “bubble baby” disease because children born with this condition lack a functioning immune system, so even a simple infection could be fatal and in the past they were kept inside sterile plastic bubbles to protect them.

In this study, published in the New England Journal of Medicine, researchers took blood stem cells from the child and, in the lab, genetically re-engineered them to correct the defective gene, and then infused them back into the child. Over time they multiplied and created a new blood supply, one free of the defect, which helped repair the immune system.

In a news release Dr. Ewelina Mamcarz, the lead author of the study, announced that ten children have been treated with this method.

“These patients are toddlers now, who are responding to vaccinations and have immune systems to make all immune cells they need for protection from infections as they explore the world and live normal lives. This is a first for patients with SCID-X1.”

The ten children were treated at both St. Jude and at UCSF and CIRM funded the UCSF arm of the clinical trial.

The story, not surprisingly, got a lot of attention in the media including this fine piece by CNN.

Oh, and by the way we are also funding three other clinical trials targeting different forms of SCID. One with UCLA’s Don Kohn,  one with Stanford’s Judy Shizuru, and one with UCSF’s Mort Cowan