By Anna Edney
(Updates with sales figures in sixth paragraph)
Nov. 18 (Bloomberg) -- U.S. regulators revoked approval of Roche AG's Avastin as a treatment for metastatic breast cancer, a move the drugmaker has said could put as much as 800 million Swiss francs ($873 million) in revenue at risk.
Avastin, with $6.2 billion in 2010 sales, didn't extend patients' lives and triggered serious side effects including high blood pressure and bleeding when used to attack the disease, said Commissioner Margaret Hamburg of the Food and Drug Administration in a statement today. The drug remains approved for colon, lung, kidney and brain cancer.
In June, Avastin failed to win backing at a first-of-its- kind advisory panel that was requested by Roche after the FDA first suggested approval be revoked. In that hearing, patients urged the advisers to continue access. The U.S. Centers for Medicare and Medicaid Services and the health insurer WellPoint Inc. said they would review today's action.
"This was a difficult decision," Hamburg said. "FDA recognizes how hard it is for patients and their families to cope with metastatic breast cancer and how great a need there is for more effective treatments. But patients must have confidence that drugs they take are both safe and effective for their intended use."
Roche declined 0.5 percent to close at 142.60 Swiss francs in Zurich.
Study Continues
Avastin's worldwide sales for the first nine months of this year totaled 3.9 billion Swiss francs ($4.3 billion), according to company filings. Sales dropped 8 percent compared with the same period last year.
The decision will lead insurers, including the government's Medicare and Medicaid programs for the elderly and poor, to reconsider Avastin coverage policies, said Len Lichtenfeld, deputy chief medical officer at the American Cancer Society. Women who are already on the drug and benefitting from it shouldn't be taken off, he said.
While Roche doesn't plan to appeal the decision, it will continue a study seeking to identify breast cancer patients who would benefit most from Avastin, said Charlotte Arnold, a company spokeswoman, in an e-mail. The study will weigh whether higher levels of a protein in the blood known as VEGF-A might improve the results with Avastin.
One disadvantage of Avastin is it lacks a genetic test to predict the subset of breast-cancer patients that are likely to benefit from the treatment, said Elizabeth Thompson, president of Susan G. Komen for the Cure, an advocacy group. That's in contrast to Roche's Herceptin, which comes with a test that helps predict patients for whom the drug is very likely to work.
'Measured Risk'
"You are much more willing to take a measured risk if you are going to have a more significant benefit," Thompson said.
About 230,480 U.S. women will be diagnosed with new cases of invasive breast cancer this year and the disease will kill an estimated 39,520, according to the American Cancer Society.
Because the drug is approved for other diseases, doctors can still prescribe Avastin for breast cancer "off label."
The U.S. Centers for Medicare and Medicaid Services now covers Avastin for use against breast cancer and will "evaluate coverage options as a result of action by the FDA but has no immediate plans to change coverage policies." Don McLeod, a spokesman for the agency, said in an e-mail today.
WellPoint, Aetna
Lori McLaughlin, a spokeswoman for Indianapolis-based WellPoint Inc., also said her company would review its coverage after an analysis is published in a peer-reviewed journal.
Aetna Inc., in Hartford, Connecticut, follows the National Comprehensive Cancer Network guidelines, which recommend Avastin for metastatic breast cancer, said Mohit Ghose, a company spokesman. Aetna will also monitor peer-reviewed journals and update its policy as needed, he said.
UnitedHealth Group Inc. in Minnetonka, Minnesota, follows the Comprehensive Cancer Network guidelines, said Lynne High, a spokeswoman for the company.
In February, Roche said that a negative decision could mean a loss of 800 million Swiss francs ($873 million), and Gbola Amusa, a London-based analyst with UBS AG., said the decision is "absolutely consistent with consensus expectations."
Hamburg outlined her decision in a 69-page opinion that determined the use must be removed from Avastin's product labeling. The drug was approved for metastatic breast cancer in February 2008 under the condition additional trials show effect on tumor growth.
The data showed minimal results on tumor growth without evidence patients lived longer or had a better quality of life compared with standard chemotherapy, FDA said.
Advisory Panel's Vote
The FDA advisory panel voted 6-0 on June 29 that Avastin should be taken off the market for breast cancer because it doesn't prolong survival enough to outweigh the significant risks.
The medicine generated 6.46 billion Swiss francs ($6.22 billion), or 14 percent of Basel, Switzerland-based Roche's revenue last year.
The FDA first moved to withdraw Avastin's breast cancer use in December after reviewing the results of clinical studies the agency said showed the drug didn't prolong life or slow disease progression enough to outweigh risks, including severe high blood pressure, bleeding and hemorrhage, heart attack and the development of holes in the nose, stomach and intestines.
"None of the studies demonstrated that patients receiving Avastin lived longer and patients receiving Avastin experienced a significant increase in serious side effects," Janet Woodcock, director of the agency's drug center, said at the time.
Outcry From Patients
The decision sparked an outcry from some cancer advocates and patients who testified at the panel hearing urging the FDA to allow the medicine to retain its approval. Roche protested the agency's withdrawal plan and appealed.
Woodcock encouraged Roche to conduct more studies to find select groups of patients who might benefit from the drug. The Swiss drugmaker had suggested as a compromise that the agency restrict Avastin's use in breast cancer to patients with a more aggressive form of the disease who don't have many other treatment options. European regulators decided to maintain Avastin's use in breast cancer.
Today's decision wasn't the first time the FDA curbed use of a cancer drug. In 2005, the agency restricted use of AstraZeneca Plc's lung cancer treatment Iressa to patients who were already taking the medicine after trials showed didn't help patients live longer.
HER2 Gene
Avastin received its tentative approval in combination with the chemotherapy paclitaxel as an initial treatment for metastatic breast cancer, which means the cancer has spread to other parts of the body. The drug was indicated for 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.
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 generic versions of the drug entered the market in November.
--With assistance from Catherine Larkin in Indianapolis, Makiko Kitamura in London, Michelle Fay Cortez in Minneapolis and Robert Langreth in New York. Editors: Adriel Bettelheim, Chris Staiti
To contact the reporter on this story: Anna Edney in Washington at aedney@bloomberg.net
To contact the editor responsible for this story: Adriel Bettelheim at abettelheim@bloomberg.net
