This story sounds too far-fetched to be true. The FDA knowingly pulls a drug off-label used by 17,500 women for an incurable disease, many using it as a last ditch effort to stay alive. Among those are women doing remarkably well on the drug. Worse, the decision is made under questionable circumstances, by a "death panel", possibly of unqualified individuals, avoiding established procedures, while defying precedent and common sense.

Instead of giving these women a say, the FDA tells them that they cannot speak at a final hearing on this drug, where the jury will be the identical people who "convicted" them previously. This has all the drama of a murder trial, with knowingly innocent women about to be sentenced without being able to utter a word. The big difference is that when the verdict is rendered, these women will not, like the usually less innocent on death row, have endless appeals. This verdict will be final.

More than 40,000 women in the United States died of metastatic breast cancer (MBC) in 2009. Avastin, a unique drug for women with MBC, was granted accelerated FDA approval in 2008 subject to further successful trials by the drug's manufacturer, Genentech. The FDA rejected the results of these follow up trials finding insufficient evidence of benefit relative to the risks. The aforementioned and unprecedented hearing is set at the FDA for June 28th & 29th, 2011, where the current FDA decision is under appeal by Genentech.

The removal of Avastin from on-label to off-label status affects the estimated 17,500 women currently on the drug plus potential future users of Avastin. Avastin is the only approved antiangiogenic drug for MBC, meaning that the drug interferes with blood flow, essentially starving tumors of their life-line. Some women have seen dramatic results after being on the drug for years, many after failing with multiple if not all alternatives. These super-responders, who would normally not be expected to live this long, have been ignored by the FDA, who have chosen instead to concentrate solely on statistics and on the average results.

Should current Avastin patients cease to obtain the drug, many will die premature deaths. Should the FDA confirm its decision without in some way grandfathering in current patients, Medicare and private insurance companies will be loath to continue to provide coverage for an off-label drug. As the cost of the drug varies from about $56,000 to $96,000 per annum, only the wealthy will obtain their Avastin while the rest won't. Genentech appears to want to help the truly needy by donating Avastin for free but the FDA has some new policies whereby drug companies and their employees may face liabilities for donating a drug off-label. This appears to be scaring Genentech from being more generous with compassionate use donations.

The FDA has not played by the rules and worse, has altered them in the middle of the game. Avastin met the initial requirements in its follow up trials only to have the FDA change the endpoints that it considered acceptable for drug approval. But this is only the tip of the iceberg.

The FDA over-emphasized the side effects by over-emphasizing rare side effects. Patients know the risks of Avastin before they begin their treatments and almost all consider the greatest risk to their lives to be not taking Avastin.

The Oncologic Drug Advisory Committee (ODAC) made the recommendation to deny Avastin its approval. The problem is that only two of the thirteen members are practicing oncologists, so they do not have the experience to fully understand the drug in usage with real patients. Cost was not supposed to be considered in the ODAC decision but one of the members I quoted with a statement to the contrary. Certain experts are of the firm opinion that the ODAC members possessed a poor understanding of clinical trials and statistics, which are extremely complicated in situations with incurable diseases where patients use multiple drug regimens over time.

The FDA has tried to discredit the original trial, which showed better results than the subsequent two. However, in these circumstances variation between trials is normal. There are also allegations that the FDA reviewer presented data in a biased manner to ODAC, so that they might have been misled.

It is clear that the FDA prized regulatory conformity over patient interests. By most objective standards, Avastin met the FDA's standard for accelerated approval. Furthermore, the drug is at least as effective and shows fewer side-effects than other drugs that the FDA has approved. If this represents the FDA's new approval standard in MBC, then this risks deterring drug development. Already the U.S. is losing competitiveness as it is now less expensive to run trials in Europe than in the U.S. We need to foster innovation, not stifle it.

It is ironic that on the same day that the European Medicines Agency (EMA) voted for use of Avastin with certain chemotherapy, the FDA voted against Avastin. The FDA and EMA evaluated the same trials data but reached a different decision. So we have the irony that a drug invented in San Francisco gets approval for use by Europeans (and Mexicans and Australians and others) but not by Americans.

In October, 2010 the U.S. National Comprehensive Cancer Network, a consortium of 21 leading U.S. cancer centers that issues evidence-based medical guidelines, reaffirmed its position that Avastin is valuable in some cases. The NCCN includes such major institutions as Memorial Sloan-Kettering in New York, Dana-Farber in Boston and MD Anderson in Houston.* See the list of members below.

A woman and her doctor should have the right to choose the treatment regimen that best suits her. Why does a woman have the right to choose medical care in some circumstance of her life but not her life-saving medication? Similarly, we owe these women the right to life, liberty and the pursuit of happiness. Denying them this right to life, denies them their ultimate civil liberty. The government needs to stop practicing impersonal medicine by remote control. We Americans need to act in a civilized manner. These patients have gone through an awful time in their personal lives; they don't need any further cruel and unusual punishment. We need to protect these women without delay. Grandfathering the current Avastin patients for access to their medications and private insurance or Medicare coverage is a good place to start.

Avastin (bevacizumab) Information

Update, 1/18/2011:
FDA has received a submission from Genentech supporting its request for a Notice of Opportunity for a Hearing. The information has been submitted to the docket (FDA-2010-N-0621) and was due to the agency by close of business today. We are at the beginning stages of this process and the agency will review the materials in order to make a determination on whether a public hearing for Avastin in metastatic breast cancer is warranted.

Avastin's indications for colon, lung, kidney and brain cancers will not be affected by this process or today's submission.

The agency will work diligently to determine the next steps for this proceeding. Avastin for use in women with metastatic breast cancer is still an FDA-approved indication.

Avastin is an injectable cancer medication that works by blocking a protein that is important for the formation of blood vessels. Since tumors rely on blood vessels to get the nutrients they need to survive, the drug is thought to work by preventing the formation of new blood vessels that feed the tumor. Avastin was first approved in 2004 for treatment of advanced colon cancer and has been approved since for advanced lung (2006), kidney and brain (glioblastoma) cancers (2009). Avastin was approved for metastatic breast cancer in 2008 under the accelerated approval program. Under the accelerated approval program, a drug may be approved based on results of clinical data that suggest the drug has an important clinical benefit. However, additional information is needed to confirm the data.

The FDA has proposed withdrawing Avastin's indication to treat women with metastatic breast cancer. The agency is making this announcement after deciding there is not enough evidence that the drug is safe and effective for this one indication. The announcement will not have any immediate effect on the approval of Avastin to treat metastatic breast cancer and there will be no change to product labeling. Since the marketing approval remains in effect, patients with breast cancer will still have access to the drug until a final decision has been made.

*The National Comprehensive Cancer Network includes: the City of Hope Comprehensive Cancer Center, Los Angeles, CA; Dana-Farber/Brigham and Women's Cancer Center, Massachusetts General Hospital Cancer Center, Boston, MA; Duke Cancer Institute, Durham, NC; Fox Chase Cancer Center, Philadelphia, PA; Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT; Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL; Memorial Sloan-Kettering Cancer Center, New York, NY; H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute, Columbus, OH; Roswell Park Cancer Institute, Buffalo, NY; Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO; St. Jude Children's Research Hospital/University of Tennessee Cancer Institute, Memphis, TN; Stanford Comprehensive Cancer Center, Stanford, CA; University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; UNMC Eppley Cancer Center at The Nebraska Medical Center, Omaha, NE; The University of Texas MD Anderson Cancer Center, Houston, TX; and the Vanderbilt-Ingram Cancer Center, Nashville, TN.

©Freedom of Access to Medicines, March 2011

Statement of Independence:
FAMEDS is an independent, nonpartisan, nonprofit organization dedicated to promoting the health and wellbeing of society. It opposes any activities that discriminate on the basis of race, national origin, color, creed, religion, sex, age, disability, veteran status, sexual orientation, gender identity, or associational preference. While all members of society including individuals, corporations, foundations and other legal entities are welcome to support FAMEDS, its mission remains strictly independent of any of its supporters unless otherwise noted.

FAMEDS does not promote the usage of any medicine, supplement or medical device. FAMEDS does promote access to the safe usage of any approved medicine, supplement or medical device deemed appropriate by a treating physician and with the consent of a fully informed patient.

Avastin is a registered trademark of Genentech.

Avastin Fight Song

Composer and performer, Andrew Katz, NYC

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