The Edmonton Protocol for the transplantation of insulin producing cells into individuals with type 1 diabetes (T1DM) has a cost per quality-adjusted life year (QALY) of ~$165,000. This is more than three times the willingness-to-pay (WTP) in Canada, and comfortably twice the WTP in the United States for many health care insurance plans. Even private payers, offering fully comprehensive plans south of the border, would struggle to find justification in its reimbursement. This is to say, its prospects for adoption are poor.
Enter stem cells.
The year is 2014. Fifteen years have passed since we first established human embryonic stem cell (hESC) lines in vitro. The generation of induced pluripotent stem cells from adult cells has become a relatively basic practice. This is to say, the global research community has considerable expertise in the derivation and manipulation of pluripotent cells. Pair this with a sound knowledge of developmental biology, a collection of very intelligent scientists, and the availability of a broad number of growth factors and cytokines to harness the differentiation potential of primitive cells, and you get protocols for the production of terminally differentiated cell types. One of which, more recently, is the beta cell.
Dr. Chris McCabe presented a modeling study on beta cell transplant for T1DM at an event in Toronto recently: “Driving Regenerative Medicine to the Market and Clinic: An Exploration of Enablers, Impediments, and Ethical-Legal Challenges.” His model incorporates 51 parameters pertaining to either cost or effectiveness. A value-of-information analysis showed quite clearly that the key driver of the model is cost. Not surprising given the health impact of beta cell transplant is known to be significant. Transplants completed thus far using the Edmonton Protocol show that beta cell transplant provides ~2.3 QALYs to patients. The value for health is clear. What was an unexpected finding was that cost-of-goods (COGS) was a relatively small component of overall cost; even despite the expensive growth factor cocktails required to derive functional beta cells, COGS paled by comparison to manufacturing costs and, in particular, the cost of life-long immunosuppression.
Based on Dr. McCabe’s research, if incorporating only COGS into the analysis, pluripotent stem cell-derived beta cell transplant costs less than $10,000 per QALY. But if lifelong immunosuppression is required, costs spike above $90,000 per QALY. (This is valuable information. It speaks to the importance of co-developing medical devices along with functional beta cells to provide immune-privileged environments for cells following transplant. ViaCyte and Sernova are both working on devices to do so.) This is not outside the realm of WTP.
The pressing question is, given the standard of care with current insulin pumps, which adequately manage the disease in the bulk of individuals with T1DM, do we need a cell therapy for diabetes? The answer to this question demands that we define a more comprehensive definition of value. We are now beginning to quantify the health and resource impact of beta cell transplant, but must also view the technology through the lens of social impact. How much value do we place on a “cure”?
In the case of patients with so-called “brittle” diabetes, who have a very unstable form of the disease, a transplant may be the only viable treatment option. Brittle diabetes is very rare (three of every 1,000 T1DM patients). So, it can be treated as an orphan indication, which may favour development of a more costly cell therapy approach. For the general T1DM population, it will be critical for developers to show regulators that immunosuppression will not be required as part of treatment.
It’s early days, but we have a clear understanding of the components that will be required for cost-effective implementation of beta cells in the clinic. The majority of current differentiation protocols for the derivation of beta cells generate progenitors, which need to mature in vivo to become fully functional insulin-producing cells. However, protocols are emerging that elucidate the generation of these cells in vitro. If these cells can be produced en masse in suspension culture to keep manufacturing and processing costs low, and biocompatible medical devices are produced to segregate cells from the host immune system, we may have a shot (no pun intended).