New renin-angiotensin-aldosterone system inhibitors face significant development challenges because conventional inhibitors are safe, effective, and inexpensive generics.
While novel RAAS modulators show preclinical promise for cardiovascular and renal diseases, their clinical development faces significant economic hurdles due to the availability of cheap, effective generic alternatives.
INTRODUCTION: Renin-angiotensin-aldosterone system inhibitors (RAASIs), including angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor blockers and mineralocorticoid receptor antagonists (MRAs), are the cornerstone for the treatment of cardiovascular and renal diseases. Areas covered: The authors searched MEDLINE, PubMed and ClinicalTrials.gov to identify eligible full-text English language papers. Herein, the authors discuss AT2-receptor agonists and ACE2/angiotensin-(1-7)/Mas-receptor axis modulators, direct renin inhibitors, brain aminopeptidase A inhibitors, biased AT1R blockers, chymase inhibitors, multitargeted drugs, vaccines and aldosterone receptor antagonists as well as aldosterone synthase inhibitors. Expert opinion: Preclinical studies have demonstrated that activation of the protective axis of the RAAS represents a novel therapeutic strategy for treating cardiovascular and renal diseases, but there are no clinical trials supporting our expectations. Non-steroidal MRAs might become the third-generation of MRAs for the treatment of heart failure, diabetes mellitus and chronic kidney disease. The main challenge for these new drugs is that conventional RAASIs are safe, effective and cheap generics. Thus, the future of new RAASIs will be directed by economical/strategic reasons.
Tamargo et al. (2017) conducted a review in Cardiovascular and renal diseases. New renin-angiotensin-aldosterone system inhibitors vs. Conventional RAASIs was evaluated. New renin-angiotensin-aldosterone system inhibitors face significant development challenges because conventional inhibitors are safe, effective, and inexpensive generics.