Roche Loss on Avastin Appeal Is Third in a Row at FDA Panel

Avastin Patients Urge FDA to Uphold Breast Cancer Approval
Nancy Haunty, a breast cancer patient, testifies in favor of Avastin during the Food and Drug Administration hearing. Photo: Joshua Roberts/Bloomberg

Roche Holding AG’s failure to persuade a U.S. panel to back Avastin in breast cancer is the third such loss for the Swiss drugmaker as it looks for new ways to expand sales of the world’s top-selling cancer medicine.

A Food and Drug Administration advisory committee voted 6-0 yesterday that Avastin’s use in breast cancer should be withdrawn because it didn’t work as well in follow-up studies and can cause deadly bleeding. Roche won conditional approval in 2008 over a similar panel’s objections and is appealing the FDA’s plan to revoke that clearance.

Chief Executive Officer Severin Schwan said last week that he expects Avastin sales to grow “mid-longer term.” Analysts such as Michael Leacock of the Royal Bank of Scotland in London trimmed $1 billion from their peak estimates after the FDA moved Dec. 16 to withdraw use in breast cancer, even as European regulators opted to continue to allow approval.

“For therapies for cancer, we are willing to accept a high rate of toxicity because the diseases we are treating are so awful,” Michael Sekeres, an FDA panel member and oncologist at the Cleveland Clinic in Ohio, said yesterday. “But that is predicated on therapy effectiveness.”

‘Off-Label’ Use

Avastin will remain on the market because it’s also cleared for lung, brain, kidney and colon tumors. Doctors can prescribe the drug “off label” in breast cancer even if approval is revoked, though insurers may no longer pay the $8,100-a-month price tag. Global sales last year were 6.46 billion Swiss francs ($6.22 billion), or 14 percent of Basel, Switzerland-based Roche’s revenue.

The shares gained 70 centimes, or less than 1 percent, to 140.7 francs at the close of Zurich trading.

“Yesterday’s announcement, while disappointing, does not come as a surprise,” Andrew Weiss, an analyst at Bank Vontobel AG in Zurich, wrote today in a note to investors. Weiss has a “buy” rating on Roche’s shares.

Avastin remains on the market for breast cancer in Europe. The European Commission approved the drug for broader use paired with Roche’s Xeloda for patients with metastatic breast tumors who aren’t suited to other chemotherapy options, Roche said today. The decision reversed an earlier recommendation.

The U.S. Centers for Medicare and Medicaid Services will continue to cover the drug for breast cancer as long as “doctors are prescribing it,” said Don McLeod, a spokesman for the Baltimore-based federal agency. “We often cover off-label uses for drugs,” he said.

Coverage Decisions

Aetna Inc., based in Hartford, Connecticut, also continues to pay for the medicine for advanced breast cancer, following the guidelines from the National Comprehensive Cancer Network in Fort Washington, Pennsylvania, representing 21 leading cancer centers, Tammy Arnold, an Aetna spokeswoman, said in an e-mail. UnitedHealth Group Inc. in Minnetonka, Minnesota also said in an e-mail it would follow NCCN guidelines and continue to cover the drug.

Indianapolis-based WellPoint Inc. will revisit its medical policy on Avastin following a final determination from FDA Commissioner Margaret Hamburg, said Lori McLaughlin, a spokeswoman for the insurer.

The FDA advisory panel took a little more than an hour for its deliberations yesterday, less than half the time allotted. The advisers also voted unanimously that Avastin didn’t have benefits in breast cancer and that its risks weren’t justified.

The decision capped two days of testimony from patients urging the panel to continue access while FDA scientists argued the drug is too dangerous. Hamburg’s final ruling is at least weeks away while the agency takes comments from the public through July 28.

Label Change

“We expect that Hamburg will support the FDA’s position and that this indication will disappear from the U.S. label,” Jack Scannell, a London-based analyst for Sanford C. Bernstein Ltd., wrote today in a note to investors. Scannell rates Roche’s shares “market-perform.”

The debate over breast cancer may shed light on how the FDA will consider future uses of Avastin such as in ovarian cancer. Roche said June 4 that the treatment delayed progression of ovarian tumors and cut the rate of death in two studies, though there was no sign of improvement in overall survival.

The FDA gave Avastin accelerated approval for breast cancer in February 2008, overruling its advisory panel, on the basis of one study that suggested the medicine, combined with chemotherapy, slowed tumor growth by 5.5 months more than chemotherapy alone. Required follow-up tests found Avastin kept cancer at bay for one to two months more than chemotherapy alone. The drug was also tied to more life-threatening side effects such as bleeding, stomach tears and high blood pressure.

Rooting for Avastin

“We all wanted Avastin to succeed, but the reality is that these studies that we’re talking about did not confirm that,” said Natalie Compagni-Portis, the panel’s patient representative from Oakland, California.

An estimated 230,480 women and 2,140 men in the U.S. will be diagnosed with breast cancer this year and 39,520 women and 450 men will die of the disease, according to the American Cancer Society.

“We are very disappointed by the committee’s recommendation and hope the commissioner does not decide to remove an important medicine for women with this incurable disease who already have too few treatment options,” Charlotte Arnold, a spokeswoman for Roche, said in an e-mail. “We remain ready to collaborate with the FDA to find a solution that is in the best interest of patients who need Avastin.”

New Theory

Roche asked that approval in breast cancer proceed while the drugmaker tests a new hypothesis that higher levels of a protein in the blood known as VEGF-A may identify patients who might derive substantial benefit from Avastin.

The drug was approved in combination with the chemotherapy paclitaxel as an initial treatment for metastatic breast cancer, or when the disease has spread to other parts of the body. The drug is indicated for use in patients without mutations of the HER2 gene linked to aggressive tumor growth, which accounted for 45,000 diagnoses in the U.S. last year, according to Roche.

About a dozen patients and family members in the audience began shouting and crying after the advisory panel’s vote, saying they’d depended on Avastin for years and had no other treatment options. Steve Walker, a St. Petersburg, Florida, scientist who lost his wife to cancer, called the hearing a sham and said the panel members were selected by the FDA to vote against the drug.

“I’m here with these breast-cancer patients to make sure they get a fair deal and they didn’t,” Walker said after the meeting. “This is outrageous.”

Seeking Meeting

Walker is co-founder of the nonprofit Abigail Alliance for Better Access to Developmental Drugs. The group doesn’t take money from drugmakers and plans to request a meeting with Hamburg or Health and Human Services Secretary Kathleen Sebelius to voice their concerns about the hearing, he said.

“This is our FDA -- doing a great job for cancer patients,” Walker said.

The panel members at the Avastin hearing were chosen by Hamburg’s office, not the drugs division that had called for approval to be revoked, said Karen Riley, an agency spokeswoman.

Eli Lilly & Co.’s Gemzar is the only other non-hormonal, first-line treatment for metastatic breast cancer approved in the last 30 years for HER2-negative tumors, Roche said. Indianapolis-based Lilly reported $1.15 billion in sales last year for Gemzar, also approved for ovarian, pancreatic and lung cancer. Lower-cost generics entered the market in November.

Eisai Co.’s Halaven won FDA approval in November for patients who have had at least two prior chemotherapy regimens regardless of their HER2 status. Those with mutations of the HER2 gene have other options, such as Roche’s Herceptin and London-based GlaxoSmithKline Plc’s Tykerb. Additional treatments for breast cancer include surgery, hormone therapy and radiation.

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