The run-up to what will be a closely watched FDA meeting this coming June to review the Avastin cancer med is prompting some interesting behind-the-scenes sparring between the agency and Roche. To wit, in a recent letter to different FDA officials, Covington & Burling attorney Michael Labson, who represents Roche’s Genentech unit, accused the FDA Oncologic Drugs Advisory Committee of bias.

Why? In his view - and obviously, the view of the drugmaker - there are concerns about “objectivity and fairness.” To underscore this contention, Labson writes in his March 10 missive that nearly all members of the committee last July voted to withdraw FDA approval for the metastatic breast cancer indication for Avastin (back story). And since then, various committee members were quoted in the media explaining why they voted as they did.

“These quotes and their prior ODAC vote on the continued approval of Avastin for MBC show that the ODAC will be participating in the new hearing having already expressed definitive views on the issues under consideration,” he writes. “This raises a very real concern about whether the ODAC’s participation will compromise the objectivity and fairness of the hearing.”

What does Roche want? Their attorney suggests the FDA tap a different committee for the two-day hearing in June, or at least supplement the committee with consultants in order to maintain a wall between the committee and the FDA’s Center for Drug Evaluation and Research. As far as Roche is concerned, having this committee preside over the June meeting “severely undercuts FDA’s separation of functions because of ODAC’s prior intimate involvement on the issues,” according to Labson (read his letter).

This is not the first time that the drugmaker has charged the FDA with being biased about Avastin. During a conference call last July, just after the FDA committee voted against maintaining the MBC indication for Avastin, Stefan Frings, the Avastin director at Roche, took a swipe at the agency and the expertise of the Oncology Drugs Advisory Committee during a conference call with analysts.

“Certainly, it is an ODAC, not an expert committee on breast cancer,” he chided. Then he tongue-lashed the agency for its choice of panel members, statistical points raised by FDA medical reviewers in their own reviews and a refusal to allow the panel to vote on a separate question concerning Xeloda data. “We certainly realize that FDA has stacked the deck against Avastin by choosing voting panel members who had been previously already negative on Avastin; by drafting a briefing booklet which reflected their view very peculiar, for example…more honing in on medians and overall rather ignoring hazard ratios; or, for example, how the questions were crafted,” Frings fumed.

He went on to say: “Immediately after the ODAC vote, we received unsolicited feedback from multiple thought leaders in the US in the field who were rather appalled what happened at the ODAC panel. So there will certainly be interactions, and we cannot speculate on the ultimate outcome. But I think we all heard that FDA during the ODAC committee rather expressed strong views” (back story here).

Some quick background: The agency 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. Roche, however, subsequently appealed the agency decision (see this and this).

The FDA, however, is standing its ground. In a series of responses to Labson, the presiding officer at CBER, wrote that “while I understand that Genentech has argued that the committee does not have appropriate expertise to address this issue, we do not interpret FDA regulations as contemplating the substitution of a different advisory committee, and we do not intend to do so. While I could add consultants to the advisory committee for this proceeding, we must face the reality that many experts in this area have already expressed a view on this issue and/òr might be considered as having conflicts because of their assoclation with one of the parties to the hearing or competitors to Genentech.

“Thus, it is possible that a decision to add consultants to the advisory committee would itself be the subject of dispute between the paries. Accordingly, we have concluded that the best way to obtain the advice of experts on these issues is fotthe paries to present those experts at the hearing itself and I do not intend to add consultants to the advisory committee” (read the letter).

And she also notes that “certain members of the committee that addressed these issues previously have rotated off the committee, and FDA anticipates that replacement members will join the committee before the June 28-29 hearing (read the latest letter here).

In a separate letter to Midthun, attorneys at the FDA’s Office of the Chief Counsel, writes that “although the ODAC voted in 2010 in favor of CDER’s proposal to withdraw the metastatic breast cancer indication for Avastin, CDER and the ODAC each exercise independent judgment. That independence is illustrated by CDER’s approval of Avastin for MBC after the ODAC voted against it in 2007.” They also chastised Roche and Genentech for objecting to withdrawal procedures under the accelerated approval, which was used to grant the MBC indication for Avastin. “If Genentech objected to those procedures, its remedy was to forego approval under the accelerated process and seek
approval under the traditional approval process,” they write (read the letter).

One final note, several points are still being dispute by Roche and the FDA, which you can read here. However, the agency has decided that public comment at the June hearing will be limited to written testimony, as opposed to time set aside for individuals to make impassioned pleas and the like.