Part III – Fifteen Cell Therapies/Stem Cell Therapies in Phase III Clinical Trials

By on April 10, 2013
A standard 12-well cell culture dish containing human stem cells placed under an inverted biological microscope for routine inspection.

Over the past couple weeks, The Dish posted two blogs that provided an overview of stem cell/cell therapies in Phase III clinical development. The blogs titled “Fifteen Cell Therapies/Stem Cell Therapies in Phase III Clinical Trials,” and “Part II – Fifteen Cell Therapies/Stem Cell Therapies in Phase III Clinical Trials,” each covered five therapies, the diseases states they are treating, the technologies they employ, and the companies who are working to bring these products to market. In Part III, we will cover the remaining five therapies.

These therapies were identified in a report from the Pharmaceutical Research and Manufacturers of America’s titled, “Medicines in Development – Biologics, 2013 Report.” In the report, 69 cell therapies were identified as having clinical trials under review with the Food and Drug Administration (FDA), including 15 in Phase III clinical trials. Of the therapies listed, nine therapeutic categories were represented and include: cardiovascular disease, skin diseases, cancer and related conditions, digestive disorders, transplantation, genetic disorders, musculoskeletal disorders, eye conditions, and other.

Adult Autologous Stem Cell Therapy (Renew) –Stem Cell Therapy

Sponsor – Baxter International

Myocardial Ischemia

Baxter International has developed an adult autologous stem cell therapy for treatment of chronic myocardial ischemia. In February 2012, Baxter announced that they were launching a Phase III clinical study for this product to evaluate safety and efficacy and according to Clinical it is still enrolling. The trial will enroll 450 patients that will receive one of the following treatments: the stem cell therapy, a placebo or unblinded standard of care. The goal of the study is to evaluate the treatment’s ability to improve exercise capacity in patients with chronic myocardial ischemia, which will be evaluated at twelve months following treatment. Secondary objectives include a reduction of angina and safety.

The product, also called Renew, is made up of CD34+ stem cells derived from the patient’s bone marrow. Cells are collected and processed then delivered back into the patient through 10 intramycardial injections into targeted areas of the heart. In a February 2012, Baxter press release the company stated that, “Stem cell processing will be conducted in GMP facilities in the United States by Progenitor Cell Therapy (PCT), a subsidiary of NeoStem, Inc.”

Myocardial ischemia happens when blood flow to heart muscle is reduced because of coronary artery blockage, either partial or complete. The blockage reduces the heart’s supply of oxygen.

NT-501 (cillary neurotrophic factor) (Renexus) – Cell Therapy (Orphan Drug) (Fast Track)

Sponsor – Neurotech Pharmaceuticals

Retinitis Pigmentosa

Neurotech Pharmaceuticals has developed NT-501 (Renexus) for treatment of Retinitis Pigmentosa (RP) and a number of other eye diseases. According to Clinical, Neurotech has completed a Phase II/III for early stage RP and a Phase II/III for late stage RP and has another trial currently recruiting. 

This product, given both Orphan Drug Designation and Fast Track Status by FDA, acts like a mini-bioreactor in the eye. Renexus utilizes an encapsulated cell technology implant to produce and release neurotrophic cytokine to treat the disease. The implant is a device that is semi-permeable and contains the NTC-200 cell line, which is a naturally immortalized retinal pigmented epithelial cell line. The cell line then secretes a biotherapeutic, in this case recombinant ciliary neurotrophic factor (CNTF). The semi-permeable nature of the device allows for nutrients to flow into the device and reach the cells and allows the recombinant CNTF to flow out. Neurotech states on their website, that implants are capable of continuously producing recombinant biotherapeutics for up to two years in the eye. After filling the implants with cells in their Rhode Island manufacturing facility, Neurotech Pharmaceuticals ships implants to ophthalmic surgeons for implantation into patients.

Retinitis Pigmentosa represents a number of inherited eye diseases that cause retinal degeneration and over time causes a deterioration of vision.

Neocart (autologous chondrocyte implantation) – Cell Therapy

Sponsor – Histogenics

Cartilage Disorders

Neocart is currently being evaluated in Phase II/III clinical trials. The Phase III clinical trial is for treatment of cartilage defects in the knee and is currently active. The product consists of an implant that is grown using the patient’s own cartilage cells and is being compared to the current standard of care, which is microfracture treatment.

To produce the product, a cartilage sample is collected from the patient in a non-weight bearing area of the joint. Chondrocyte cells are then isolated from the sample and according to Neocart’s website the cells are “harvested, seeded into a unique 3-dimensional collagen scaffold, and cultured under exacting conditions of high pressure, oxygen concentration and perfusion.” The implant takes a few weeks to produce and is then sent to the surgeon to implant into the patient. After a few months the implant integrates with the patient’s tissue.

Juvenile Chondrocyte Grafts (DeNovo ET) – Cell Therapy 

Sponsor – ISTO Technologies

Cartilage Disorders

DeNovo ET has an active Phase III clinical trial for treatment of articular cartilage lesions of the knee. The product is being compared to microfracture treatment, which is the current standard of care.

DeNovo ET is an allogeneic, scaffold-free, living cartilage implant. The product is produced using donor juvenile tissue to source the chondrocytes. The harvested cells are then expanded and a thin disk of cartilage tissue about the size of a quarter is produced for the implant. If approved, this would be an off the shelf product, so there would be minimal wait time for implantation.

According to ISTO Technologies’ website, “juvenile cartilage cells have far superior regenerative properties than adult cartilage cells,” based on the study “The potential of human allogenic juvenile chondrocytes for restoration of articular cartilage,” published in the American Journal of Sports Medicine in 2010.


MACI (matrix induced autologous chondrocyte implantation) – Cell Therapy

Sponsor – Genzyme

Articular Cartilage Defects

Genzyme’s MACI implant is an autologous implant for treatment of articular cartilage defects. MACI has completed one Phase III clinical study for the treatment of articular cartilage defects in the knee compared to current standard of care, microfracture treatement. MACI also has a Phase III clinical study enrolling by invitation to look at the five-year efficacy and safety for patients that previously received MACI treatment in comparison with patients that have received the microfracture treatment.

MACI is created by collecting a sample of cartilage from the patient, then chondrocyte cells are cultured and expanded to over ten million cells. The cells are seeded on the biodegradable ACI-Maix Membrane and after culturing is complete the implant is returned to the surgeon for implantation.


I hope that this review has been useful in identifying cell therapies that are in late stage trials. Now that you have seen all fifteen therapies, which do you think is the most promising? Which would be the most significant?