This page contains a Flash digital edition of a book.
academic and clinical focus. An academic perspective on


the adoption of cell therapies By Michael Whitaker and Lucy Foley, Newcastle University


Professor Michael Whitaker Dr Lucy Foley


The emerging cell therapy industry is beginning to demonstrate its potential for the treatment of diseases that are not readily treated using existing therapies. For example, in 2010 TiGenix received European Medicines Agency approval for Chondrocelect (cartilage repair) and Dendreon received Federal Drug Agency approval for Provenge (prostate cancer). In the same year clinical trials began for two ground breaking embryonic stem cell therapies, Geron in spinal cord injury and Reneuron in stroke. These companies have successfully negotiated the new and uncertain regulatory pathway for cell therapies.


Our research into cell therapy clinical trials highlights some biases; autologous, procedure based cell therapies are favoured by academics; 9 out of 78 company led therapies are autologous (12%) while 304 out of 502 clinician led trials are autologous (61%). Thus, although companies are not adverse to autologous cell therapies, they are perhaps more conscious of generating a cost of goods similar to that of biopharmaceuticals, thus the scalable allogeneic model is preferred. Academics are perhaps less aware of, or concerned about cost of goods.


This we believe is the fundamental difference between academically led programs and those led by industry; industry begins at the end. For industry, the disease prevalence and delivery mechanism determine the cell source whereas in an academic setting efficacy on the bench determines the beginning of a development programme that often does not look to the costs of eventual clinical delivery.


Cell therapies grown in 2-D culture can be costly because cost of goods is fixed, with few economies of scale.


In thinking about cost of goods, industry considers price. Cell therapies grown in 2-D culture can be costly because cost of goods is fixed, with few economies of scale.


This manufacturing method may be suitable for diseases with a low prevalence but would not suit a highly prevalent chronic disease such as diabetes, as the cost of production at scale will not be low enough to command a margin similar to that of biopharmaceuticals. Geron’s products in development are good examples of this. Geron has a human embryonic stem cell (hESC) line that they are able to culture then differentiate into different cell types. The company’s first product is hESC derived glial cells for spinal cord injury caused by trauma which effects approximately 12,000 people per annum in the US[1]


.


If this cell therapy is successful in clinical trials it will meet an unmet medical need for which the quality of life of sufferers is low and the cost of palliative care extremely high. This product can therefore command a relatively high price and can thus withstand a much higher cost of manufacture: a 2-D culture system will suffice.


Their second-in-line product is hESC derived cardiomyocytes for the treatment of chronic heart disease which kills approximately 460,000 people in the US per annum[2]


. This 40-fold larger market will require a


much more scalable process better served by the low footprint, lower cost 3-D culture production methods used for biopharmaceuticals. We might conjecture that, as the company works to demonstrate the safety and efficacy of their hESC line in spinal cord injury, it is also undertaking rigorous process development to move towards 3-D culture of their hESC line to service larger, lower cost future markets, such as heart disease.


Process development and scale have, to date, been largely neglected in the academic field. This may quite often lead to an efficacious cell therapy that cannot be scaled to meet demand cost-effectively. We propose that by considering three aspects of a cell therapy, namely the cell source, disease prevalence and delivery mechanism, platforms for cost-effective manufacture and therefore widespread adoption will emerge. That is, academically developed cell therapies must be developed as those in industry are, by starting with the final product requirements.


Considering these three aspects generates 12 possible routes to which each individual cell therapy can be mapped, as demonstrated in (Figure 1). We believe that mapping a cell therapy in development to one of these routes will ultimately determine the precise factors required to deliver a cost-effective cell therapy that can be widely adopted in the market place.


14 www.regener8.ac.uk


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36