FDA committee will consider evidence for ovarian cancer drug candidate

The FDA’s Oncologic Drugs Advisory Committee is holding a day-long hearing on Wednesday to examine the candidate drug olaparib, a PARP inhibitor, for treatment of ovarian cancer, despite equivocations on whether the drug is safe and effective enough.

by John Tyburski

Copyright © Daily Digest News, KPR Media, LLC. All rights reserved.

First published at Daily Digest News on June 24, 2014

Some drug classes just do not fare well in regulatory review, and the candidate ovarian cancer drug olaparib, another PARP inhibitor, is under close scrutiny in the looming shadows of rejection. The U.S. Food and Drug Administration (FDA) Oncologic Drugs AdvisoryCommittee (ODAC) is looking closely at whether the evidence for the candidate drug is strong enough to keep it under consideration for approval. The hearing is being held on Wednesday.

Olaparib is a member of the group of pharmacological inhibitors of an enzyme called poly ADP ribose polymerase, or PARP, an important protein in single-strand DNA break repairs. Many cancer cells have been found to rely more on PARP than normal cells so it has been a therapeutic target in drug development. However, the FDA has yet to approve a PARP inhibitor in the treatment of cancer.

One main point of contention between regulatory reviewers at the FDA and olaparib’s maker, AstraZeneca, a multinational pharmaceutical corporation based in London, UK, is that recent clinical data were derived from only a small number of patients. More specifically, there is concern that the patients who benefited from olaparib did so because the control group of the study, the patients that did not receive olaparib, “underperformed,” or suffered worse outcomes than normally expected.

“The small sample size of gBRCAm patients and the retrospective identification of this patient population call into question the reliability of the estimation of treatment effect,” states a briefing document by the ODAC. “[I]t is important to note that the loss of randomization and the selection of a convenient sample of patients who had available whole blood sample for retrospective testing may have led inadvertently to an unequal distribution of unknown factors that may have affected the study results.”

In other words, the ODAC suspects that some potential confounding factors, characteristics in patients that may influence how well they do with their cancer independent of therapy, were not properly identified and taken into consideration.

The ODAC will also carefully consider the risks involved with taking olaparib and offer a recommendation on how safe the drug may be. Approval decisions do not have to follow committee recommendations, but they almost always do.