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FDA Breakthrough Therapy Designation: 2013 In Review

December 23, 2013

As most of the Blog’s readers already know, FDASIA, or the FDA Safety and Innovation Act (S. 3187) is enacted after President Obama signs it in July 2012. FDASIA is a big step towards developing effective and safe treatments for rare diseases and orphan drug development in the United States. The legislation is to have an important and large impact on the future of accelerating new medical treatments for patient access.

It is in Section 902 of FDASIA, that the new FDA Breakthrough Therapy Designation (BTD) is described. To expedite the development and review of drugs for life-threatening and serious diseases, the FDA had three programs before the BTD is created :

•   Fast Track
•   Accelerated Approval
•   Priority Review.

The three Designations are in existence for at least 20 years. What is different about the BTD is the “ … requirement of early clinical data demonstrating an unprecedented effect …”. In order for a drug to  receive the BTD, the sponsor must provide, per Section 902 of FDASIA :

•   Evidence that the drug is intended , alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition, and

•   Preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

In January 2013, Vertex Pharmaceuticals announces that the company is awarded the 1st two FDA BTDs for orphan drug Kalydeco (Ivacaftor) for the treatment of Cystic Fibrosis (CF). Less than 1 month later, in February 2013, Pharmacyclics announces that the company is awarded the 1st two FDA BTDs for oncology – orphan drug Ibrutinib. From that point forward, as of today December 22 (all BTD #s, unless otherwise noted, includes CDER + CBER) :

•   Total # of FDA BTDs granted is 36 (35 CDER + 1 CBER)

•   28 of the 36 BTDs have       been identified by the sponsor companies

•     8 of the 36 BTDs have not been identified by the sponsor companies

•   27.3 %    of the total # of BT Requests Received results in the BTD being granted

•   21.2 % of the total # of BT Requests Received results in the BTD pending

•   51.5 % of the total # of BT Requests Received results in the BTD being denied.

While BTDs for new drugs did take off at CDER, FDA’s CBER in comparison is not moving as fast as CDER in approving applications. Out of 15 CBER BTD applications received :

•   Only 1 BTD is granted
•   12 or 80% are denied, compared to 48% denied for CDER BTD applications
•   2 are still pending.

Other trends to note about the FDA BTDs in 2013:

•   The first BTDs receive FDA approval starting in November, with 2 approvals for oncology drugs and 1 approval for Hepatitis C

•   12 of the 28 BTDs (identified by sponsor companies), or approximately 43% are for oncology indications (blood cancers are included).

Also, important to note that out of the total 68 CDER + CBER BTD applications denied, only one sponsor company has come forward to report a BTD denial. In August 2013, Ariad Pharmaceuticals at their Q2 2013 Earnings conference call, publicly discloses that a BTD application is denied. The company discloses that the FDA denied BTD for the company’s AP26113, for the potential treatment of Anaplastic Lymphoma Kinase-positive (ALK+) Non-Small Cell Lung Cancer (NSCLC). According to the company, the BTD is denied because of the “relatively short follow-up” and the small number of ALK+ patients. Ariad Pharmaceuticals submitted to the FDA, data from only 24 evaluable patients in the Phase I portion of a Phase I/II trial, which resulted in 14 partial responses and 1 complete response in a Xalkori-naïve patient.

Below is a chart of upcoming 2014 FDASIA tasks from FDASIA-TRACK for BTDs :



Deliverable       Type

Deliverable Description

Target Date

FDA Lead       Organization

IX 902 Draft Guidance Implementation  requirements for   Breakthrough Therapies 1/9/2014 CDER
IX 902 Final Guidance Implementation requirements for Breakthrough   Therapies 7/9/2014 CDER


As the FDA BTD matures over the next year, the FDA, sponsor companies, and other stakeholders will learn more about the BTD process, the impact on time to approval, impact on the total drug development cycle, and what impact, if any it will have on the cost of the drug to the consumer and insurance companies.



FDA BTD Approval Chart

FDA BTD Statistics Chart.

Please Note: “IMG Carlingford Lough 0617” by By Sarah777 at en.wikipedia [Public domain] | Wikimedia Commons.

Copyright © 2012-2013, Orphan Druganaut Blog. All rights reserved.


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