Accelerated Approvals in Oncology A 10 Year Experience

1
Accelerated Approvals in Oncology A 10 - Year
Experience
2
Purpose

• Review past accelerated approvals
• Discuss current progress of associated phase 4
  commitments
• Solicit input for improving the process

3
Outline

• Oncology product AA from CDER and CBER
• Regulatory background
• Approvals based on controlled trials lacking a
  concurrent comparator
• Approvals based on randomized studies
• Converted indications
• Issues for the committee

4
Overview

• 19 NDAs or BLAs for new treatment indications
  (involving 16 drugs)
• Seven within l8 months of meeting invitation
• Subsequent full approval in 4
• Remaining 8 to be presented over next two days

5
Regulatory Basis - Subpart H (21CFR 314)

• For serious or life-threatening diseases
• Where the drug appears to provide benefit over
  available therapy
• Approval based on a surrogate that is reasonably
  likely to predict clinical benefit

6
21CFR314 (continued)

• Subject to the requirement that the applicant
  verify and describe benefit
• Post-marketing studies would usually be underway
• The applicant shall carry out such studies with
  due diligence

7
Endpoints in Oncology

• Survival and improvement in patient reported
  symptoms considered clinical benefit
• Objective Response Rate and Time to Progression
  usually viewed as surrogates
• RR representing benefit relatively non-toxic
  products such as hormonal therapies or some
  biologics

8
Approvals (no concurrent comparator)
9
Approvals (no concurrent comparator)
10
Approvals(no concurrent comparator)
11
Approvals(randomized trials)
12
Approvals(randomized trials)
13
Endpoints Utilized

• No concurrent comparator ORR
• Randomized setting Cytologic response, number
  of polyps, ORR, TTP, DFS, LVEF CHF

14
Uncertainty of Benefit to Ultimate Outcome

• Amifostine (Ethyol)
• Dexrazoxane (Zinecard)
• Anastrozole (Arimidex)
• Imatinib mesylate (Gleevec)
• first-line CML

15
Timing of Confirmatory Trials Converted
Indications
16
Sponsor Presentations
17
Protocol Issues

• Has accrual been satisfactory ?
• If not, what strategies can address this ?
• Have changing circumstances impeded the conduct
  of a planned trial ?
• If so, what alternative designs should be
  contemplated ?