OBJECTIVES: In 2012, the United States Food and Drug Administration (FDA) created a new expedited pathway of  “Breakthrough Therapy Designation” (BTD) to enable an early approval of therapies which have shown substantial activity in early trials. The objective of this study was to assess the comparative effectiveness and pricing of drugs with BTD. METHODS: The data for the number of granted BTDs was obtained from FDA.gov. The data for publically disclosed BTDs was obtained from sponsor’s press releases.  For all products, the information for their mechanism of action, type of molecule, trial design, clinical efficacy and safety, and pricing and time to approval (for approved products) were obtained from peer-reviewed publications, conference abstracts, FDA and sponsor websites. RESULTS: Since the establishment of the BTD pathway, 55 products have been granted breakthrough therapy designations (2012-2014), of which, 42 have been publically disclosed by the manufacturers and 6 have been approved by the FDA. In terms of indications, 43% are for cancer, 18% are for genetic diseases and 14% are for Hepatitis C Genotype 1. The median time to approval for these three drug was ~5 years, significantly shorter than the 2012 median time to approval for priority review applications (6 years). The price premium was 30-50%, compared to other drugs in the same category. The six approved BTDs show 20-30% higher response rates than other products in the same category. The other products in the pipeline with established comparators show 36%-136% improvement in efficacy (based on active controls or previous trials). For approximately half of the products, comparative efficacy cannot be determined because of no previous evidence for a product with efficacy in the targeted indications. CONCLUSIONS: BTD is a promising pathway to shorten development time and provides early access, however, the high price could pose challenges for payers and patients.