Two stem cell therapies have received approval in other countries, but none so far in the United States. In 2011, FCB-Pharmacill’s Hearticellgram-AMI was approved in South Korea for treatment of Acute Myocardial Infarction. Then in May 2012, Canada approved Osiris’ Prochymal for treatment of Graft vs. Host Disease, which was then followed in June by approval for the product in New Zealand. Prochymal is currently under fast track review with the Food and Drug Administration and is in Phase III clinical trials.

While there have been no approvals in the United States, there are many stem cell therapies currently in clinical trials. In this blog we will review ten companies that have made significant progress with stem cell therapies in clinical trials. The purpose of the blog is to give an overview of stem cell therapies in clinical trials, the diseases states they are treating, the technologies they employ, and the companies who are working to bring these products to market. We will look at five companies in part I and the remaining companies in part II. Advanced Cell Technology Advanced Cell Technology (ACT) has two stem cell therapies in Phase I clinical trials. ACT’s lead products are focused on treatment of different forms of retinal degeneration, specifically Dry Age Related Macular Degeneration (Dry AMD) and Stargardt’s Macular Dystrophy. Dry AMD affects more than 30 million people worldwide and eventually leads to blindness. ACT believes this application represents a $25-30 billion dollar market. Stargardt’s Macular Dystrophy is a juvenile macular degeneration that impairs the vision of children and young adults. This treatment is in Phase I trials under both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) and has been granted Orphan Drug status by both.

In both treatments ACT uses retinal pigment epithelial cells derived from human embryonic stem cells (hESCs). According to a recent ACT presentation at BIO “hESC-derived products will be manufactured using a cell line made in 2005 from single cell, isolated without the destruction of any embryos.” The cells are manufactured under GMP conditions and then are injected into the patient’s eye. A recent study published in the Lancet, showed that the ACT treatment for macular degeneration was successful in that cells attached and persisted, pigmentation was increased, and functional visual improvement was reported. In addition there were no signs of hyperproliferation, abnormal growth or rejection of the cells. Neostem Neostem has three Cell Therapy product divisions. One of these divisions, Amorcyte has a product in Phase II clinical trials. The product AMR-001 is a treatment for acute myocardial Infarction (heart attack). The product is designed for patients who have suffered the more dangerous type of heart attack called ST-Elevation MI (STEMI) that has resulted in reduced Left Ventricular Ejection Fraction of less than 50%. In these patients the heart attack causes so much damage that remaining heart muscle cannot maintain healthy heart output and this puts these patients at a higher risk for further heart attacks, complete heart failure and premature death. These types of heart attacks affect around 160,000 people per year and Neostem estimates that this represents an annual market of over $1.2 billion dollars.

AMR-001 uses autologous bone marrow-derived adult stem cells administered 5-11 days post heart attack. In the Phase I study, it was determined that a threshold dose of 10 million cells was sufficient to cause significant improvement. Aastrom Aastrom has two cardiovascular products in clinical trials. Their lead product is a treatment for Critical Limb Ischemia currently in Phase III clinical trials with a Fast Track Designation from FDA. Critical Limb Ischemia (CLI) is a severe form of Peripheral Artery Disease (PAD). PAD is caused by a narrowing of the arteries due to plaque build up also known as “hardening of the arteries” or the medical term atherosclerosis. PAD results in reduced blood flow to the legs, feet, and hands. CLI is the most serious form of the disease with patients often suffering from gangrene, skin ulcers, and loss of feeling or use of the limb. Treating CLI is difficult often resulting in amputation and CLI has a high mortality rate. Aastrom states that there are 1-2 million Americans with CLI and this treatment represents a $2 billon dollar market.

Aastrom’s second product is a treatment for Dilated Cardiomyopathy (DCM) that has completed a Phase II clinical trial and has received Orphan Drug Status from FDA. DCM is a disease of the heart muscle and is the most common cause of heart transplantation. It is also a common cause of complete heart failure. The DCM treatment represents a $1 billion dollar market.

Aastrom manufactures its autologous stem cell product under cGMP conditions. Manufacturing capacity is currently at 3,000 patients per year. Aastrom manufactures the product by taking a bone marrow sample from the patient, then isolating and expanding primarily CD90+ mesenchymal cells, CD14+ monocytes and alternatively activated macrophages. The cells are then delivered back to the patient either intramuscularly (CLI) or through endocardial catheter injections (DCM). Culture and expansion of the cells takes 12 days and administration to patient happens within 3 days of manufacture. Pluristem Pluristem has two cardiovascular products in clinical trials. The first is a treatment for Critical Limb Ischemia that is in a multinational Phase II/III trial. The second product is a treatment for Intermittent Claudation (IC) and is in Phase II clinical trials. Intermittent Claudation is a milder form of PAD where patients experience pain but only while exercising or walking, while at rest the pain goes away. IC affects about 14 million people worldwide.

In August 2011, Pluristem received Orphan Drug Status for treatment of Buerger’s Disease. According to a recent Pluristem press release, the company recently filed for Orphan Drug Status for Aplastic Anemia after successfully treating a 7 year old girl in Israel. The girl whose condition was critical “experienced a reversal of her condition with a significant increase in her red blood cells, white blood cells and platelets following the intramuscular injection of the company’s PLX cells.”

Pluristem’s stem cell product is called PLX cells and is made up of mesenchymal-like adherent stromal cells derived from full-term placentas. After the cells are harvested they are expanded in large scale bioreactors, stored for future use and administered to patients when treatment is necessary. Athersys Athersys has four products currently in clinical trials. The first is a product to treat Inflammatory Bowel Disease (IBD), which includes Crohn’s Disease and Ulcerative Colitis. This product is being developed in partnership with Pfizer and is currently in Phase II clinical trials. IBD is an inflammatory disease that affects the colon and small intestine. This disease causes abdominal pain, weight loss, vomiting and diarrhea in patients. IBD affects more than one million Americans.

Their second product for Graft vs. Host Disease (GvHD) has completed Phase I clinical trials and has received Orphan Drug Status from the FDA. GvHD can occur during stem cell or bone marrow transplants. The immune cells present in the transplant view the cells in the patient receiving the transplant as foreign and begin to attack the patient’s tissues and organs. GvHD can cause serious disability and can even be fatal. It is a frequent complication and occurs in about half of transplants. Athersys estimates that this is a $500 million – $2 billion dollar market annually.

Their third product for Ischemic Stroke is currently in Phase II clinical trials. Ischemic Stroke occurs when there is an arterial blockage and blood flow cannot reach the brain. Ischemic Stroke represents more than 85% of all strokes according to the American Heart Association (AHA). AHA also states that about 795,000 Americans suffer a stroke each year, that stroke is the fourth leading cause of death, and a leading cause of disability in the United States. Athersys states that their product addresses an unmet need and represents a market opportunity of over $15 billion dollars per year.

Athersys’ fourth product for Acute Myocardial Infarction is currently in Phase II clinical studies. The product, administered after a heart attack, is designed to improve overall outcomes and reduce risk of Congestive Heart Failure.

Athersys employs an allogenic technology called Multistem. Multistem is comprised of human stem cells derived from adult bone marrow or other non-embryonic tissue sources that have been expanded and frozen for later use. Athersys has prepared Multistem as an “off the shelf” treatment and they state that the frozen product is viable for years. During scale up they state that they are able to generate “hundreds of thousands to millions of doses per donor.” According to Athersys “MultiStem consists of a special class of human stem cells that have the ability to express a range of therapeutically relevant proteins and other factors, as well as form multiple cell types. Factors expressed by MultiStem have the potential to deliver a therapeutic benefit in several ways, such as reducing inflammation, protecting damaged or injured tissue, and enhancing the formation of new blood vessels in regions of ischemic injury. These cells exhibit a drug-like profile in that they act primarily through the production of multiple factors that regulate the immune system, protect damaged or injured cells, promote tissue repair and healing, and the cells are subsequently cleared from the body over time.”

I hope that this review has been informative as to the types of therapies being developed with the use of stem cells. It certainly was very interesting for me and I was impressed with the advances being made in this area. I will post part II of this blog next week with 5 additional companies covered.

In the meantime, what do you think will be the next stem Cell Therapy approved? Which is the most significant?

For further information on stem cell manufacturing, please see our previous stem cell series: