Women's Right To Choose Avastin Debated During House PDUFA Hearing

Discussion of the status of Avastin's indication for metastatic breast cancer at a July 7 House hearing can be seen as a surrogate for several debates that could unfold during the user fee reauthorization process – including FDA approval standards, conflict-of-interest screening for advisory committees and pricing.

Rep. Sue Myrick’s support for continued approval of Avastin for metastatic breast cancer came through loud and clear during her questioning of Center for Drug Evaluation and Research Director Janet Woodcock.

The North Carolina Republican, a cancer survivor, conceded the toxicities associated with the Genentech oncology drug and that it does not work for everyone.

But, Myrick persisted, “if it is helping some people and they are willing to take the risk … should we not allow them to have that opportunity?”

Myrick is one of several Republicans who have raised the specter of economics as the underlying reason for CDER’s push to withdraw approval of Avastin (bevacizumab) for metastatic breast cancer ( (Also see "Avastin Down, But Not Out Yet In Metastatic Breast Cancer Indication" - Pink Sheet, 20 Dec, 2010.)

During the House hearing, the topic of which was Prescription Drug User Fee Act reauthorization, medical innovation, jobs and patients, Rep. Phil Gingrey, R-Ga., pushed Woodcock to rule out cost as a factor in the decision (Also see "Woodcock Defends Speed Of FDA Reviews, Cites 20 Approvals In First Half Of 2011" - Pink Sheet, 7 Jul, 2011.).

FDA never looks at the cost of a drug because “it’s not within our mandate,” Woodcock insisted.

Women’s Right To Choose

During the hearing, Myrick’s focus was a woman’s right to choose risk.

For some, she stressed, Avastin “does extend their survival. Metastatic breast cancer patients are facing a deadly disease and many are willing to take that toxicity risk if the drug helps keep them alive.”

So, she asked Woodcock, “why can’t the FDA approve the drug with appropriate warnings for doctors and patients by informing the doctors that many of their patients might not respond and that there are risks involved?”

Woodcock declined to comment on Avastin in particular since it is the subject of ongoing decision-making, but explained that a drug that saves lives will be approved, “regardless of many serious side effects, as long as the survival advantage is not outweighed by mortality caused by the side effects.”

In the case of Avastin, the trials showed “no survival advantage at all,” she said.

That does not mean Avastin does not work for some women, Woodcock noted. “It may well be that if they could come up with a biomarker to say these women are the ones who should take this drug, then it might be possible to figure out who the drug is good for.”

Conducting such a trial does not appear easy, however (see related story, (Also see "Genentech Losing Its Legs? Avastin Study Proposal Undercut By Feasibility, Scientific Concerns" - Pink Sheet, 11 Jul, 2011.)).

Biomarkers and screening tests to identify those helped by Avastin may come in the future, Myrick said, but “if we don’t have the screening tests now, I don’t think we should restrict access or pull approval simply because we’re not sure how to define the category of patients who will respond.”

European Approval Standards

Myrick also questioned how different regulatory agencies can reach different decisions based on the same information.

While FDA is preparing to withdraw Avastin, the drug is widely available in Europe for metastatic breast cancer, she noted. FDA and the European Union have reviewed the same data, she said. “What’s the difference?”

Woodcock acknowledged that “we do look at all the same data. We certainly talk to the EU about their decisions.”

In the case of Avastin, the VEGF-inhibitor is approved for brain cancer in the U.S. but not in Europe. “Sometimes various experts come to different opinions,” she said.

In a discussion with Rep. Mike Rogers, R-Mich., Woodcock clarified that FDA does not tell physicians they cannot prescribe a drug. “Avastin is on the market for other indications and will remain on the market,” she pointed out.

Advisory Panel Composition

Rep. Michael Burgess, R-Texas, gave no clear opinion on the withdrawal decision but questioned the makeup of the advisory committee convened to review the breast cancer claim.

Looking at the roster for the panel, which had six voting members, Burgess pointed out that “I don’t see anyone that would have had ongoing daily treatment of breast cancer patients under his or her control. You have a lot of experts and a lot of oncologists, but I didn’t see a specific specialist in the specialty of metastatic breast cancer. Wouldn’t you want someone like that on a panel” weighing this type of decision?

Woodcock only commented that “this was not run by the center for drugs. … I agree there was no breast cancer expert, to my knowledge, on that panel.”

Burgess had earlier complained about provisions in the FDA Amendments Act that limit the number of participants on an advisory committee who can have waivers from conflict-of-interest regulations.

For some drugs and indications, there may only be one or two experts in the field and they need to able to share their knowledge regardless of conflicts, he said.

The upcoming user free reauthorization process offers Congress the opportunity to potentially reform the conflict-of-interest requirements, but political dynamics seem to be steering the legislation towards a "clean" version (see related story, (Also see "Not Another FDAAA – Observers Expect Fewer FDA Reforms In PDUFA V" - Pink Sheet, 11 Jul, 2011.)).

By Cathy Dombrowski