Welcome to your Update from the Clinic for the month of November. NeoStem announced initial positive data from its Phase 2 study in acute myocardial infarction. Neuralstem’s human neural stem cells are shown to have long-term viability following transplant, while Fibrocell is given clearance for an investigational new drug (IND) application to develop a treatment for war veteran amputees. Read on to find out more.
New York-based NeoStem (NBS), which is developing CD34 cells for ischemic repair and immunotherapies for cancer, reported on initial results from the PreSERVE clinical study in acute myocardial infarction (AMI). Statistically significant effects were observed in mortality benefit and in the correlation between cell dose and ejection fraction. Major adverse cardiac events (MACE) decreased with increasing cell doses. MACE occurred in 15% of patients receiving less than 14 million cells and 7% of patients receiving more than 20 million cells.
Unlike many cell therapy companies, NBS has the luxury of using its own contract cell manufacturer – Progenitor Cell Therapy (PCT) – to produce cell doses. NBS bought PCT in a strategic acquisition in January 2011. Robert Preti, NeoStem’s Chief Scientific Officer and President of PCT, emphasized that PCT has been working on scaling the NBS10 technology and optimizing cost-of-goods at its Engineering and Innovation Centre, a division of the company that exists to address limitations in cell manufacturing by designing new technologies and developing therapies in parallel. (The cell doses NeoStem used in the PreSERVE study are at the lower end of the therapeutic dose range, which should also help keep costs down.)
In 2011, Neuralstem (CUR) launched a first-in-human Phase 1 study investigating human spinal cord stem cells for the treatment of amyotropic lateral sclerosis (ALS). In a recent study published in the Annals of Clinical and Translational Neurology, the company was pleased to provide evidence of the long-term survival of NSI-566 cells, which survived for two and a half years in some patients. Individuals in the study (n=6) received only temporary immunosuppression following transplant, indicating that continued immunosuppression is not necessary for survival. This finding has positive implications for reimbursement, should the therapy be approved in the future.
Here’s an unusual cell therapy. Fibrocell (FCSC) is developing a treatment for war amputees to prevent stump skin diseases. Individuals with amputations from battle-related injuries receive prosthetics, but many are forced to abandon them due to skin deterioration and pain at the point-of-contact between the limb and prosthetic. In an autologous approach using a sub-type of fibroblast known as a volar fibroblast (those found on the palm or foot), Fibrocell is attempting to promote transformation of skin in these sensitive areas to make it more robust. Genetically modified volar fibroblasts will be used to introduce keratin-9 into affected areas, helping to thicken the outermost layer of skin.
Immunocellular Therapeutics (IMUC) gave an update on maturing data from its Phase 2 study of ICT-107, a dendritic cell-based immunotherapy being developed for patients with glioblastoma multiforme. As per previous analyses, progression free survival (PFS) results continue to be significant between treatment and control groups. However, the effect is strongest in a subset of patients that have the MGMT gene marked with methyl groups (PFS benefit is 15.6 months). This benefit is reduced to only 4.5 months in unmethylated patients.
IMUC’s stock plummeted in December 2013 following release of the study’s initial results, which showed that ICT-107 was clearing the PFS hurdle but not having a significant impact on overall survival (OS). While OS data are available for the unmethylated patient population, they are not yet available for methylated patients as the median has not yet been reached. This will be the crux of IMUC’s clinical development of ICT-107 and likely the decider in whether the program will be halted or moved to Phase 3.
In hopes of one day transplanting whole organs, Cellular Dynamics International (CDI) has teamed up with a physician at Northwestern University’s (NWU) Feinberg School of Medicine to complete the first step in bringing this paradigm to fruition: recreating the blood supply infrastructure. Using CDI’s iCell endothelial cells, Jason Wertheim, assistant professor in Surgery-Organ Transplantation, was able to coat the blood supply system of a human kidney scaffold. Without addressing blood supply, the construction of artificial organs will not be possible. There is a large unmet need in organ transplantation. More than 120,000 individuals are on wait lists, a number that increases by one every 10 minutes.
That brings a close to clinical developments in 2014. Here’s a recap of some of the notable news from the RM industry this year:
- Northwest Biotherapeutics became the first company to receive a “Promising Innovative Medicine” (PIM) designation by the UK Health Authorities for its DC-Vax immunotherapy for glioblastoma multiforme; DC-Vax also became the first immunotherapy to be granted a hospital exemption under German drug law;
- Neuralstem successfully transplanted the first patient in a Phase 1/2 study investigating its neural stem cell product NSI-556 for the treatment of motor deficits arising from ischemic stroke, while bluebird bio transplanted its first patient with sickle cell disease;
- BioTime subsidiary Asterias Biotherapeutics received FDA clearance to launch a Phase 1/2 study of AST-OPC1, a cell therapy composed of embryonic stem cell-derived oligodendrocyte progenitors, in patients with cervical spinal cord injury ;
- OncoMed commenced its third Phase 1b study investigating OMP-54F28, a fusion protein, in patients with ovarian cancer, and initiated its Phase 2 ALPINE study investigating Tarextumab in patients with pancreatic cancer;
- Athersys’ MultiStem product failed in a Phase 2 study of patients with severe ulcerative colitis; no significant benefit was observed between treatment and control groups; and,
- StemCells completed enrollment of 12 patients in a Phase 1/2 investigating its neural stem cell product Hu-CNS-SC in patients with thoracic spinal cord injury; the company also announced positive interim data for the cell therapy in AMD.
More updates in the New Year. Enjoy the holidays!
Disclaimer: “Update from the Clinic” is a blog post generated by news flow from public regenerative medicine (RM) companies around the globe. As CCRM has public RM companies in its industry consortium, and the number of such companies is relatively limited on a global scale, Mark Curtis will sometimes include CCRM consortium members in his review. This blog post is provided for general information only and nothing contained in the material constitutes a recommendation for the purchase or sale of any security. The author is not a shareholder of any public RM company. To see a list of CCRM’s industry consortium members, please visit http://ccrm.ca/industry-consortium