Drug development can be a science of extrapolation if the use of a drug exposure-response relationship is embraced and implemented through mechanistically oriented pharmacokinetic (PK)-pharmacodynamic (PD) modeling analysis and clinical trial simulation. The traditional requirement of at least 2 adequate and well-controlled phase III studies by the US Food and Drug Administration for drug approval can be waived in certain situations, substantially reducing the resources and time. In this article, the authors introduce a real drug development case where the chance for this exemption was maximized by actively using PK-PD modeling followed by clinical trial simulation, resulting in faster and more economical introduction of a new dosage regimen to patients.