A New Drug Approval Pathway - Breakthrough Therapy Designation

Recently, a new drug approval pathway proposed by FDA has drawn attentions to many pharmaceutical/biotechnology companies. Last year, The Food and Drug Administration Safety and Innovation Act (FDASIA) included a provision that allows sponsors to request that their drug be designated as a Breakthrough Therapy. Breakthrough status means the companies will have closer communication with top FDA staff to move drugs for serious diseases to market more quickly, potentially with data from an expanded Phase 1 trial.

• US FDA announces first Breakthrough Therapy Designations
• Innovative Drugs May Win U.S. Approval After Early Trials- Novartis grabs FDA's coveted 'breakthrough' status for lung cancer drug
• Pharmacyclics Gains ‘Breakthrough’ Status for Cancer Drug
• Pfizer's Palbociclib Receives Breakthrough Therapy Designation for Breast Cancer Treatment

Only a small portion of drugs can obtain the Breakthrough Therapy designation. The drugs for treating the serious diseases with unmet medical needs may be easier to obtain the Breakthrough status. The drugs targeting the small sub-population of certain disease may also be qualified for Breakthrough Therapy designation (see the example for Vertex' Kalydeco). The clinical trial that designed to target the small sub-population is called enrichment clinical trial design (i.e., choosing sub-population that is likely to respond to the study drug, therefore design a smaller study) . See recent FDA guidance.

Only a small portion of drugs can obtain the Breakthrough Therapy designation. The drugs for treating the serious disease with unmet medical needs may be easier to obtain the Breakthrough status. The drugs targeting the small sub-population of certain disease may also be qualified for Breakthrough Therapy designation (see the example for Vertex' Kalydeco). The clinical trial that designed to target the small sub-population is called enrichment clinical trial design (i.e., choosing sub-population that is likely to respond to the study drug, therefore design a smaller study) . See

recent FDA guidance.

FDA Existing Drug Approval Pathways are:

• Accelerated approval for serious disease with unmet medical need. Approval with surrogate endpoint with commitment for confirmatory trial with clinical endpoint.
• Orphan drug status or orphan drug designation for rare diseases
• Restricted distribution Approval with restrictions to assure safe use
• Priority review FDA completes review within 6 months versus standard review time of 10 months
• Fast track review to facilitate the development, and expedite the review of drugs to treat serious diseases and fill an unmet medical need
• Breakthrough drug designation see above
• the Generating Antibiotics Incentives Now (GAIN) Act. For antibiotics

In addition, there is a movement for Patient oriented drug development (i.e., the study endpoint should measure ‘feel, function, or survival’ of the patients). See

FDA presentations on this topic.

In EU, the Adaptive Licensing is gaining more interests. The idea of Adaptive Licensing is to allow a drug to be launched onto the market with certain restrictions, based on its benefit/risk profile. Those restrictions could then be gradually removed as more positive data is forthcoming and more favorable benefit/risk profile. However, in US, there is no movement about Adaptive Licensing isea.  

Attached is FDA's Development & Approval Process (Drugs)

•  How Drugs are Developed and Approved
•  Drug and Biologic Approval Reports
•  NDA and BLA Approvals 
•  NME Drug and New Biologic Approvals
•  ANDA (Generic) Drug Approvals
•  Priority NDA and BLA Approvals
•  Efficacy Supplement Approvals
•  Accelerated and Restricted Approvals 
•  NDA Approvals by Therapeutic Potential and Chemical Type
•  Fast Track Approval Reports