Report card for accelerated FDA approval oncology drugs (1995-2003): is it time for a make-up test?

Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 6, 2004

Presenter: S.M. Belknap
Presenter's Affiliation: Northwestern University, Chicago, IL
Type of Session: Scientific

Background

The FDA approval process includes multiple pathways. One of these is the accelerated approval that was adopted in 1992 in order to improve access to new drugs. The accelerated approval requires that the investigational drug is better than the existing treatments for a serious illness and is based on studies that evaluate surrogate markers.

Materials and Methods

This analysis was performed by reviewing new onclogy licensing applications and supplements for new uses approved by the FDA from 1995 to September 2003. Data collected included: application filing data for individual agents, date of approval, types of studies assessed during FDA review, and endpoints used in these studies.

Results

21 oncologic indications received accelerated FDA approval
5 indications were converted to regular approval after submission of subsequent studies [capecitabine, dexrazoxane, docetaxel, imitinab mesylate, irinotecan]. 2/5 studies included <200 patients.
3 indications were submitted for regular approval but rejected by the FDA . 2/3 studies included <200 patients
13 indications have not been submitted. 11/13 studies included <200 patients
Surrogate outcomes included response rate (n=16), symptom improvement (n=1) and reduced time to recurrence (n=1)
14 approvals were based on results of phase II clinical trials. 5 approvals were based on phase III studies
Post-marketing studies identified serious adverse events for four of the drugs, three of which had an incidence >10% and were identified within 7 months of initial FDA approval (capecitabine-associated interaction with warfarin, imatinib-associated hemorrage in GIST, and gemtuzumab-associated VOD).

Author's Conclusions

Accelerated approval of drugs infrequently converts to full approval
62% of accelerated approval indications are based on clinical trials involving <200 patients
Safety data are often incomplete
Accelerated approval may not offer greater benefit over expanded access programs

Clinical/Scientific Implications

The accelerated approval process was adopted to improve access to new drugs and requires that the investigational drug is better than the existing treatments for a serious illness and is based on studies that evaluate surrogate markers. This analysis reviewed new onclogy licensing applications and supplements for new uses approved by the FDA and analyzed application filing data for individual agents, date of approval, types of studies assessed during FDA review, and endpoints used in these studies. Two major concerns are that accelerated approval of drugs infrequently converted to full approval and safety data are often incomplete. The risk/benefit ratio of accelerated approval is not optimal. A more adequate number of patients and a better reporting of safety data and efficacy may be possible solutions or well designed EAPs may be more effective in the drug development process.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.