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