12-1-2014 - Pink Sheet - Breaking Down Breakthrough Requests

12-1-2014 - Pink Sheet - Breaking Down Breakthrough Requests

by Derrick Gingery
 

FDA’s evaluation of the first two years of the breakthrough therapies program found common threads among designation requests that were granted and denied, which may help sponsors better understand the agency’s criteria for awarding the incentive.

Below are key characteristics of products that have gained and were denied breakthrough designation, as well as reasons why FDA turned down a sponsor's request for breakthrough status.

Product Characteristics

Category

Breakthrough Designees

Breakthrough Denials

Average enrollment of trials submitted in request

184.3 (median: 88)

114.4 (median: 51)

Average number of trials submitted in request

1.52

1.23

Maximum trial phase

1.94

1.73

Request included randomized or blinded trials

56% randomized/32% blinded

56% randomized/46% blinded

Available therapy for the disease

64%

49%

Rare and/or orphan

60%

55%

Genetic/targeted therapy

38%

20%

Note: Based on total of 50 breakthrough designations and 86 denials analyzed

Genetic Component To Therapy

Type of Therapy

Designees

Denials

With a genetic component in the indication

19

17

No genetic component in the indication

31

69

Orphan vs. Non-Orphan

Status

Designees

Denials

Median enrollment in highest trial phase submitted with orphan status

69

47

Median enrollment in highest trial phase submitted without orphan status

161

56

Alternative Therapies Available

Availability of Alternative

Designees

Denials

Approved and unapproved therapy available

9

10

Only approved therapy available

23

32

Only unapproved therapy available

14

28

No alternative therapy available

4

16

Maximum Trial Phase Of Evidence In The Designation Request

Phase

Designees

Denials

0

2

1

1

9

27

2

29

47

3

10

7

No data submitted

0

4

Median Trial Enrollment

Phase

Designees

Denials

1

19

28

2

73

62

3

161

147

Other (requests that included expanded access data)

16

31

 

Reasons for Denial of a Breakthrough Designation

Total denials reviewed

86

Lack of efficacy

57 (66%)

Lack of safety

14 (16%)

All data or trial problems

80 (92%)

No clinical data

5 (6%)

Trial design flaws

22 (43%)

Invalid endpoint

25 (29%)

Sample size

31 (36%)

Post hoc analysis

13 (15%)

Trial results too preliminary

21 (24%)

Treatment effects not isolated

10 (12%)

Concomitant treatments

3 (3%)

Miscellaneous or other reasons

17 (20%)

Source: Presentation by CDER Director Janet Woodcock during the Nov. 21 Friends of Cancer Research-Brookings Conference on Clinical Cancer Research

https://www.pharmamedtechbi.com/Publications/The-Pink-Sheet/76/48/Break…