Despite weeks of haggling, Roche and the FDA remain unable to agree on the questions that must be addressed during the upcoming June hearing that will be held to decide whether the agency will proceed with plans to remove the metastatic breast cancer indication for the Avastin. The two sides are so far apart, in fact, that each one has submitted separate documents summarizing their differing views of the key questions to be addressed.

Some quick background: The FDA decided to yank the breast cancer indication after results of four clinical studies showed that Avastin does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh significant risks. These include severe high blood pressure; bleeding and hemorrhage; development of perforations in the body, including in the nose, stomach, and intestines; swelling of the brain, and heart attack or heart failure (see this).

That move came after an FDA advisory panel voted to withdraw the approval, which was originally made under the agency accelerated approval program (see here). The about-face raised questions about accelerated approval, given that the FDA requires two randomized, controlled trials to demonstrate safety and effectiveness before approval, but oncology drugs can sometimes get a pass under this program (read this and this). Roche, meanwhile, subsequently appealed the agency decision, setting the stage for the June 28 and 29 hearing.

But the drugmaker and the agency remain far apart on how to proceed. For instance, the second of three questions the agency believes should be addressed asks whether the “totality of the data submitted to the BLA (Biologics License Application) and reviewed by CDER show that Avastin is safe and effective for its MBC indication.” The FDA, basically, wants to know if the Roche data proves whether Avastin offers a sufficient risk-benefit profile, although the agency also asks whether the Center for Drug Evaluation & Research appropriately exercised its authority to push for withdrawal rather than allow Avastin to remain with an MBC indication will additional studies are conducted (see this).

Separately, Covington & Burling attorney Michael Labson, who represents Roche’s Genentech unit, writes in his own letter that “studies consistently show an efficacy benefit…and it is agreed that the safety profile is well-characterized with no new safety signals in the subsequent MBC studies.” And he goes on to question whether the Avastin decision would be consistent with other FDA approval and withdrawal decisions, not just whether the agency is acting appropriately.

Labson also couches the issue in the context of providing options for patients while more studies are run. This has resonated among many women, some of whom petitioned the FDA last year to allow the MBC indication to remain (look here). And he poses a different question that attempts to put the FDA on the defensive: “Are FDA’s actions on Avastin likely to facilitate or deter the future development of treatments for first-line metastatic breast cancer?” In other words, Roche wants to use the forum to send a signal that, if the FDA revokes the MBC indication, who knows where the agency will stop.