Thesis Abstract

The Accelerated Approval Process in Oncology:
An Examination of the Conversion Rate of Approved Therapies to Full Approval

(By Jean Jinsun Kim)
 
Abstract
In 1992, Accelerated Approval, or Subpart H approval, was added to the NDA regulations so promising products that provide a meaningful therapeutic benefit for serious or life-threatening diseases could be introduced to the market sooner, particularly for diseases or conditions where there was a great unmet medical need. Accelerated Approval is based on either a surrogate endpoint that is reasonably likely to predict clinical benefit or a clinical endpoint other than survival or irreversible morbidity. After approval, the sponsor is required to perform post-marketing studies to demonstrate clinical benefit.

Since the FDA expanded the use of the Accelerated Approval regulatory path to include oncology drugs in 1995, thirty drugs (both small molecule as well as biologics) have been granted accelerated approval in oncology. However, from various reports in the literature and the FDA site, it appears that only a small fraction of these approvals (four(1) to six(2)) have been converted into regular approvals, based on the demonstration of clinical benefit in the post-marketing studies that support the benefit seen in the pivotal studies.

In my research, I examined the basis of approval for six drugs that were converted to full approval and compared this group to the seven drugs that received accelerated approval before 2000 but as yet have not converted to full approval. The six drugs that were converted to full approval, with the exception of dexrazoxane, completed their post-marketing requirements in 2.3 years after initial approval. The sponsors, who were all well-capitalized pharmaceutical companies, also pursued additional indications for these drugs.

In the group of drugs that were designated as “not converted” by several sources, two of the drugs have been granted full approval within the past year. And in March 2006, the FDA withdrew its accelerated approval for one drug based on the results of a negative clinical trial. Six years after having received accelerated approval, two drugs in this group are still undergoing clinical trials. Due to the lack of information about the ongoing trials, it is difficult to assess the underlying reasons for the delay in attaining full approval. But the sponsors of these two drugs are small biotechnology companies, while all of the sponsors of the drugs that have been converted to full approval are major pharmaceutical companies.

A majority of the drugs that converted to full approval were granted a broader label based on the post-marketing studies, which demonstrated clinical benefit in a wider patient population than originally tested.

While the accelerated approval process holds many advantages in that companies can introduce their drug to the market sooner, the requirements for accelerated approval often result in the drugs having to meet ‘a higher standard’ in that they have to demonstrate “meaningful clinical benefit” over existing agents, which may in fact be a requirement for superiority, as was seen in the case of one agent, Doxil. The post-marketing studies can be expensive and difficult to complete, but companies with ample resources and sufficient incentives, such as additional potential indications, seem able to clear this hurdle easily.

 
  1. FDA website: www.accessdata.fda.gov/scripts/cder/onctools/Accel.cfm
  2. Dagher R, Johnson J, Williams G, Keegan P, Pazdur R. Accelerated Approval of Oncology Products: A decade of experience. Journal of the National Cancer Institute, 96, 20, 2004, 1500-1509.
 

Thesis Co-Supervisor: Ernst Berndt
Title: Louis E Seley Professor of Applied Economics, MIT Sloan School

Thesis Co-Supervisor: Anthony J. Sinskey
Title: MIT Professor of Biology and Harvard-MIT Professor Health Science and Technology

Thesis Co-Supervisor: Frank L Douglas

Request copy of thesis: cbi@mit.edu.