Proceed with Caution
Many technical hurdles remain to be overcome, notably cryopreservation and manufacturing, Dr. Langer observes. “Every tissue/organ has its own issues to solve.”
From Dr. Niklason’s perspective, “The two real stumbling blocks for the industry have been manufacturing (repeatability, reproducibility, and scaling) combined with cost of goods issues. But these are becoming a dragon that can be slain.” While the regulatory environment is not getting easier, she observes, “cell products are less of an unknown for the FDA than they were a decade ago, so there is more precedent for the FDA to regulate products and the number of complete surprises is fewer.”
“The evolving regulatory environment and affordability of healthcare, both in the U.S. and abroad, will continue to pose significant hurdles,” says Dr. Gemmiti.
“That said, speaking from personal experience, the FDA was very willing to work with us at Organogenesis on the recent approval of Gintuit™, our new living cellular sheet for the regeneration of oral soft tissue. The lessons learned through that successful process are already helping to educate the rest of the field. On the healthcare side, companies committing to evidence-based medicine and supporting that with health economics research will find themselves ahead of the pack in the future.”
When asked how the regulatory environment for tissue-engineered and stem cell products has evolved over the past four years, Dr. Gemmiti replied, “In certain instances, the amount of clinical evidence required to support the safety and efficacy of biologics and devices has increased.” However, he points to products such as Provenge, LaViv™ (Fibrocell Science), and Gintuit as “important examples to follow and set precedents, at least on the cell-based side.”
“Unquestionably, the FDA’s aggressive stance with respect to cell-based therapeutics is a dramatic hurdle,” says Dr. McAllister. For at least some applications—and he mentions the use of stem cell-based therapies to treat congestive heart failure and muscle loss associated with acute myocardial infarction as examples—“the risk/benefit analysis is dramatically skewed and, as an industry and a regulatory body, we should be revisiting our cumulative tolerance of risk.”
In 2005, for example, coronary heart disease caused 1 out of every 5 deaths in the U.S. The prevalence of heart failure in the U.S. was about 5.7 million, and mortality attributable to heart failure exceeded 292,000 per year. Mortality due to myocardial infarction (MI) was about 151,000 in 2005, and about 1 in 5 people 40 years of age or older who suffered a first MI would die within a year. “These patients have little hope of improvement with current therapies,” says Dr. McAllister.
An Evolving Industry
The 2012 analysis included a detailed breakdown of spending by industry segment and stage and found that stem cell-based therapies dominate both the clinical (73%) and preclinical (62%) stages, followed by the category of cells and biomaterials (with clinical spending representing 18% of the total, and preclinical 19%). “These data suggest that stem cell-based products and combination products (cells and biomaterials) will be entering the market in the next 5–10 years,” concluded the authors.
“Of particular note is the entrance of embryonic stem cell (ESC)-based therapies into clinical trials for the first time.” The report noted that among companies developing stem cell-based therapies, 59% of those products derived from autologous cells and 39% from allogeneic cells, while 2% utilized xenogeneic cells. The majority (58%) of companies favored adult stem cell technologies, while 10% specialized in ESCs; the other 32% included in the analysis offered stem cell banking services.
Dr. Langer feels that the decision of whether to develop an ESC- versus adult stem cell-based therapeutic, or an autologous versus allogeneic therapy, should be decided on a case-by-case basis depending on the problem you are trying to solve and the properties of each type of cell. The choice between embryonic and adult stem cells will depend largely on which is likely to be most efficacious for a particular application; whereas the decision to work with autologous or allogeneic cells encompasses rejection issues, the need to grow cells without risk of de-differentiation, and how quickly the cells are needed.
“I think allogeneic cell therapies will always have an edge over autologous cell therapies,” says Dr. Niklason. “To contemplate an autologous cell therapy, the benefit to the patient has to be enormous.”
With regard to ESCs versus adult stem cells, “when the dust settles, embryonic stem cells will have taught us a tremendous amount,” says Dr. Niklason. “They have been critically important tools and enabling for the current overall stem cell field.” For the purposes of human therapy, however, she expects that adult stem cells and iPS cells will play a predominant role.
Looking forward, the authors, editors, and members of the Industry Council as a whole are cautiously optimistic. They express confidence in the industry’s ability to continue its upward trajectory and maintain a positive growth trend, while not minimizing the challenges that lie ahead.
“I see the field continuing to grow and becoming more entrenched as a viable industry,” says Dr. Gemmiti. “The setbacks of the past have provided important lessons for everyone: companies, investors, and regulators. The field can continue to translate research into viable products, deliver much-needed therapies to patients, and further establish successful businesses.”