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Genentech, CDER Tussle Over Avastin Hearing Panel And Format
The Pink Sheet Daily
By Sue Sutter
March 28, 2011

In a sign of the uphill battle Genentech faces in retaining Avastin's breast cancer claim, the company's efforts to shape the panel and format for a June 28-29 hearing on the indication's withdrawal are encountering strong opposition from FDA's Center for Drug Evaluation & Research.

Genentech continues to push for its case to be heard by experts other than, or in addition to, FDA's Oncologic Drugs Advisory Committee, which voted against the breast cancer indication in 2007 and 2010. However, CDER says that by agreeing to accelerated approval in the first place, it now cannot object to the convening of ODAC pursuant to that process.

The parties also disagree on the extent of public participation at the June hearing. The company wants FDA hearing official Karen Midthun to allow oral comments from members of the public, presumably so that it can use emotional patient testimony on the drug's effectiveness to bolster its case for keeping the breast cancer indication. However, CDER maintains there has been "ample opportunity" for input without an open public hearing at the upcoming meeting.

Hearing Parameters

In February, FDA granted Genentech's request for a hearing on the proposed withdrawal of the Avastin (bevacizumab) accelerated approval in metastatic breast cancer. FDA Commissioner Margaret Hamburg tapped Midthun, director of the Center for Biologics Evaluation and Research, as the presiding officer for the two-day hearing.

In a Feb. 24 letter, Midthun outlined the parameters and submission deadlines for the hearing and described the internal firewall that has been established between herself and CDER.

In response to Genentech's request for "an objective advisory committee with substantial breast cancer expertise," Midthun said she was convening the existing oncology advisory committee because FDA believes its accelerated approval regulations do not allow for substitution of a different panel. She rejected Genentech's request that additional experts be added to ODAC, concluding that many breast cancer specialists had already expressed views on the matter or might be considered to have conflicts of interest.

Genentech attempts to use this same argument in a March 10 letter requesting that Midthun reconsider her decision.

Written by Genentech's counsel, Michael Labson of Covington & Burling, the letter states that all but two of ODAC's current members were present at the July 2010 meeting, where the panel voted 12-1 to withdraw the indication.

"Even though Genentech intends to present information at the hearing that was not considered by the ODAC, these ODAC members have already expressed a clear opinion on much of the data and voted against maintaining approval of the MBC indication."

The letter recites comments various ODAC members expressed in media reports after the July meeting. "This raises a very real concern about whether the ODAC's participation will compromise the objectivity and fairness of the hearing," Labson writes.

As an alternative to convening a different panel, Genentech again requests other experts be appointed to supplement ODAC. Futhermore, "given that the ODAC comes to the hearing essentially aligned with CDER," the committee and CDER should share their time allotted for questions, Labson writes.

Genentech also requests Midthun reconsider allowing oral presentations from the public. "The robust public response and numerous submissions to the public docket (including a large number from MBC patients) demonstrate the strong public interest and the need for public participation in this matter," the letter says.

Genentech's requests drew a rebuff from CDER. In a March 22 letter to Midthun, Office of Chief Counsel attorneys Carla Cartwright and Abby Brandel say CDER disagrees with the suggestion that ODAC is "essentially aligned" with the center.

FDA's approval of the breast cancer indication despite ODAC's initial vote against it reflects the independent judgment of both, CDER said.

ODAC's role in the hearing is to provide advice and recommendations to Midthun and the commissioner, the attorneys say. "Moreover, 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."

Genentech Made Its Bed

The OCC letter also reflects a view that Genentech made its bed and now must lie in it.

When FDA created the accelerated approval process, it contemplated a standing advisory committee that had previously reviewed a drug would participate in any hearing on its withdrawal, the letter says. "Genentech agreed to the accelerated approval of the MBC indication for Avastin, and cannot now object to the withdrawal procedure that applies to products approved under that framework."

CDER also supports Midthun's decision to limit public participation at the hearing. There has been "ample opportunity for public participation in this matter," the letter says, noting that oral presentations were permitted at the 2007 and 2010 ODAC meetings and members of the public may file written comments to the hearing docket.

"Given the streamlined process intended for this hearing and the time constraints under which the agency is operating, allowing additional public testimony could take time away from scientific discussions and deliberations."

Deadlines Have Been Extended

Although Midthun has not yet responded to Genentech's March 10 letter, she did grant the parties' joint request for a 15-day extension of various deadlines.

The joint statement of facts is now due on April 7, with a written summary of arguments each side intends to present at the hearing due on May 5. Genentech and CDER also have an additional deadline – they must identify their hearing witnesses by May 27.

Avastin Fight Song

Composer and performer, Andrew Katz, NYC

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