As an increasing number of stem cell therapies advance through clinical trials, the healthcare industry’s focus comes to looking at which cells, allogeneic or autologous, are more likely to be commercially feasible. Proving safety and efficacy for a specific indication is a large enough challenge for any treatment, but for stem cell therapies in particular, commercial viability may be just as big a hurdle.
Israel-based Pluristem Therapeutics (NASDAQ:PSTI), may be the only stem cell company that can mass produce immune-privileged allogeneic cells at a scale and price that not only makes them commercially viable, but moreover makes stem cell therapy a preferred method of treatment for patients and payors alike. A proprietary 3D stem cell expansion technology which uses placental-derived cells is the key.
A 2015 article in Cell Stem Cell estimated there were 352 registered clinical trials evaluating the use of stem cell products across nine indication categories. The U.S. FDA has only approved one stem cell treatment and that’s for cord blood-derived hematopoietic progenitor cells for certain indications. Pluristem is entering late stage trials in three indications with its allogeneic placental-derived cells.
The benefits and disadvantages of autologous versus allogeneic cells have been core to the decision-making of cell therapy providers and researchers from both a developmental and commercial standpoint.
Autologous versus Allogeneic Stem Cell Therapies
The most important benefit of autologous cells, which are harvested directly from patient, expanded ex vivo, and then reinserted back into the patient, is that they are least likely to create harmful and life threatening graft versus host disease (GvHD) or expose the patient to a new infection from the donor. The primary disadvantage, particularly in the treatment of cancer, is that when stem cells are collected, cancer cells may be collected along with them, and may then be inadvertently reinserted into the body during treatment.
Also in terms of treatment, the time consuming process involved in expanding autologous cells makes them unsuitable for use in the emergency room or other acute circumstances. However, even if an autologous stem cell treatment proves to be safe and effective and receives FDA approval, the economics and logistics of autologous cells may be insurmountable. Treating each patient with their own stem cells is very expensive, time consuming, and does not lend itself to standardization and consistency in treatment results. Autologous cells imply stem cell therapy needs to be a service-based business model, which creates challenges in terms of FDA approval and reimbursement.
In contrast, allogeneic cells, which originate from a donor, are expanded and then used to treat a patient in need. The drawbacks to this approach include a higher chance of GvHD and other complications, because the donor cells may attack the patient’s cells, resulting in more harm than benefit. This is where Pluristem’s placental cells are unique.
Cells from the placenta, due to their organic function in the mother’s body to feed another human being, are immune-privileged, meaning placental cells are far less likely to attack another human’s cells as a foreign body. By design, placental cells are made to support and grow another human being. Placental cells, which are ethically collected by Pluristem from the afterbirth of donors, are found in abundant supply, with each placenta facilitating over 20,000 doses of 300 million cells. No tissue matching and no immunosuppression drugs are required to administer Pluristem’s placental-derived PLX cells.
The benefits of allogeneic cells include:
- Scalability of production
- Standardization in the manufacturing and cell expansion processes
- Use as an off-the-shelf product
- Use in acute and emergency room settings
Additionally, one industry study published in BioPharm International found autologous cells would cost more than double that of allogeneic, although cost factors can vary widely depending upon the kind of autologous and allogeneic processes that are used.
A key differentiator for Pluristem is its patented 3-dimensional cell culturing technology which allows for efficient, controlled production with batch-to-batch consistency of different cell products in commercial quantities. Pluristem’s PLX-PAD cells are manufactured in its state-of-the-art GMP and CMC facility which can produce 150,000 doses annually. The U.S. FDA, as well as health regulatory agencies from Europe, South Korea, Japan, and Israel have all approved Pluristem’s cell manufacturing process for Phase II, III trials and marketing. PLX cells have an impressive shelf life of over 3 years.
While Pluristem has not yet divulged the pricing for its PLX cell therapies, given their efficient manufacturing process, the costs may be very favorable as compared to the standard of care in the indications the company is pursuing. With a global Phase 3 trial in critical limb ischemia set to commence patient enrollment in the first half of 2017, the industry may see sooner, rather than later, the benefits of placental-derived allogeneic cells.