Approaching Regulatory Approval of Cardiovascular Regenerative Therapy.

Abstract

> For the race is not always to the swift …. > > —Aesop (600–564 BC) After 25 years of research and well over a decade after the first randomized blinded clinical trials suggested benefit of stem cell therapy on cardiac performance, the field seems no closer to clinical approval of a product, and skepticism exists about the viability of the idea that myocardial regeneration can be effected. What has kept the field from crossing the finish line of clinical approval and is the goal in site? From a regulatory perspective, the efficacy and safety of regenerative approaches remain unproven.1 Despite significant expenditures of time and funding, definitive adequately powered trials have yet to be completed. Many of the challenges in the field of myocardial regeneration reflect obstacles in cardiovascular drug development as a whole. Improvements in the treatment of cardiovascular disease have resulted in dramatic reductions in cardiovascular mortality and have extended the life span of patients with cardiovascular disease but have also resulted in an increased prevalence of chronic conditions like congestive heart failure and refractory angina. These improvements in care have paradoxically increased the burden of disease and need for new therapies while exponentially increasing the number of patients required to demonstrate effectiveness. Recent estimates indicate that the cost of bringing a new drug to market increased from $140 million in the 1970s to >$2.5 billion in 2014 and tripled in the past decade alone.2 The implications of this can be seen in an example from the field of heart failure: although the CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study; published in 1987) proved a mortality benefit of angiotensin-converting enzyme inhibition after following up 253 patients for 6 months, the benefit of sacubitril/valsartan in 2014 required enrollment of >8000 patients and 27-month follow-up to demonstrate an effect on …