Development of Oncology Products

Yesterday's session on oncology drug development focused on updates and improvements among dialogue and harmonization between the FDA and EMEA and featured presentations from both. In those presentations, it was established that both agencies feel that relationships across the waters are well, it is the relationships between each agency and the drug sponsors that could use a little more harmony. It was a presentation from an academic investigator that generated a look into simplifying industry processes in order to more quickly further drug advances.

Hans-Georg Eichler, MD, MSc, senior medical officer with the EMEA, presented data on its oncology drug approvals. Between 1995-1999, 20 drugs were approved. In 2000-2004, 28 were approved and from 2005-2008, 55 oncology drugs have been approved. Eichler submitted that this is a testament that research is actually translating into better treatments for patients. Further, based on data, he suggested that randomized clinical trials vs. single arm trials actually improve the chances that a drug will be approved in the EMEA in that the approval rate for the randomized clinical trials were 81% vs. 53% for the single-arm. Approvals for rare cancers by the EMEA have grown faster than for other cancers.

Eichler believes that the agreement between EMEA and FDA for confidential dialogue among the regulatory agencies to harmonize the oncology drug approval process is working. What is working less in his view is the ability of sponsors to utilize a parallel or joint scientific advice/meeting process with both EMEA and FDA to facilitate a more unified process. In the discussion period, Eichler said he believes the sponsors “seem happy with separate meetings” and then they play us against each other, i.e., “Well, EMEA said that we could do it this way.”

Robert Justice, MD, MS, director, office of oncology drug products for CDER, FDA, also presented data on oncology drug approvals from 2005-2008, which included a total of 53 drugs. Of that, 37 were tested in a randomized control trial, and 16 were in a single-arm.

Justice stated his views on where improvements in the oncology drug approval process could be found. The pre-IND phase suffers from inadequate preclinical models that do not help to identify products that will be successful in the larger Phase III trial. In pre-NDA, he thought that meetings were not used enough to discuss the adequacy of clinical study results to support approval.

Also, Justice said, "I think SPAs (Special Protocol Assessments) are over-utilized. An SPA doesn't guarantee approval." He believes an SPA is appropriate for uncommon diseases where there are no precedents or few endpoints and directed sponsors to the final guidance on Phase III endpoints at www.fda.gov/cder/guidance/7478fnl.htm.

Views from Academia
Bradley Monk, MD, associate professor, Division of Gynecologic Oncology, Chaos Family Comprehensive Cancer Center (CFCCC), University of California, Irvine Medical Center, began his presentation with food for thought: Swine flu has killed 160 people worldwide this year, 250,000 women will be killed worldwide from cervical cancer in one year. “I think we are in peril,” said Monk. He said that the peril is not from Iran, North Korea or the swine flu. He said, “We are in danger of cancer.”

Monk believes among other things, is the complicated approval process coupled with clinical trial execution complexity that is hampering advances in cancer. For example, he cited the clinical trails development process at CFCCC. In the step-by-step guide, sponsors must submit to six different committees. He also cited a Journal of Clinical Oncology article from April 2009 that said there are 296 distinct processes required for Phase III trial activation.”

Monk said, “I’m not saying we should take risks,” however, he believes that redundant steps, the clinical trials complexity, and regulatory delays negatively impact the process.

He said that people at his hospital have asked him, “Why would you do a trial when you are losing money?” He answered, “Because my family gets cancer, your family gets cancer.”