On Friday, we posted a press release from Breast Cancer Action (Breast Cancer Action: Patients Lose, Genentech Wins with FDA’s Avastin Ruling) criticizing the FDA’s approval of Genentech’s [NYSE:DNA] Avastin for treatment of metastatic breast cancer. We noted that it was odd that the FDA approved this drug, given that the Oncologic Drugs Advisory Committee (ODAC) had recommended. Applications for drugs to be approved for new uses are first sent to Advisory Committees comprised of physicians with expertise in that speciality (here, oncology). If the Advisory Committee recommends that the drug not be approved, the FDA usually approves it — and if it advises that it not be approved, then the FDA usually doesn’t. As an article in BioWorld Today (FDA Splits with ODAC, OKs Avastin Use in Breast Cancer) describes, the vote of the ODAC was close, but serious concerns were still raised by it:

The approval came as somewhat of a surprise, considering that the FDA usually follows the advice of its advisory panels. Although the ODAC vote on Avastin in breast cancer had been close, at 5 to 4, the panel had raised concerns about trial design, toxicity and survival data.

Breast Cancer Action raised some serious concerns about the FDA’s accelerated approval of Avastin for metastatic breast cancer in its press release which we posted on Friday. Barbara Brenner, Breast Cancer Action’s Executive Director, raises some additional concerns about the approval — not about the drug itself, but about how the drug was approved, and based on what type of clinical trial. In an email to advocates (reprinted here with her permission), she describes the danger:

I want to give folks some context for what happened here, particularly in light of the recommendation of the ODAC some weeks ago that the drug not be approved at this time. BCA encouraged that outcome. See the first story on the home page at http://www.bcaction.org/ for the history.

What happened today is that the Commissioner of the FDA, Andrew Von Eschenbach caved to enormous pressure from industry. Some of you have seen the Wall Street Journal editorial yesterday saying that it would be a “moral tragedy” if the drug weren’t approved because lives were at stake, even though there is no evidence that the drug improves survival. What we know is that the head of Genentech met with the WSJ editorial board last week. And they’ve been dribbling out little bits of data about other trials that also don’t have survival data.

The FDA Commissioner, as you know, is never bound by an ODAC recommendation. In this case, the Commissioner Von Eschenbach is as tied to industry as the rest of the Bush administration is.

As you can see from Genentech’s press release , we are very sad that that industry’s interests have trumped those of patients in the case of this particular drug, and that they have evidently acceded to a lower standard of drug approval — PFS (progression free survival) — instead of overall survival.

But the standard has been changed in another critically important way as a result of today’s decision. Before today, a drug could not be approved for marketing unless it had been subjected to a drug registration trial with standards set by the FDA. This standard is higher than the standard for classical clinical trials, largely because routine clinical trials often mask the true side effects of drugs or are done in populations that are likely to result in overstated benefit.

The decision made today was on the basis not of a registration trial, but of an NCI-sponsored clinical trial, not designed for drug registration. This means that, in the future, other drugs companies will be able to argue to the FDA (probably successfully) that the FDA drug registration standards don’t have to be met, basing approval on clinical trials will be just fine.

As I sat last week trying to figure out why Genentech had not even mentioned the AVADO trial (the one that was designed as registration trial, the results of which were expected in the first three months of this, and were in fact partially released last week, one week before the decision today) in their Avastin presentation to the ODAC in December, I came to a stunning realization: what Genentech was hoping for was a decision that would permit drugs companies to avoid the rigors of registration trials in the future, and rely on clinical trials that are often controlled by industry. And that is what they got with today’s decision.

The bar has been lowered in more ways than we can count. A very sad day for patients.

The BioWorld Today article described above gives some of the history:

In May 2006, Genentech submitted a supplemental biologics license application to the FDA seeking approval of Avastin in breast cancer. But the FDA raised concerns about the underlying data, which had not come from a traditional double-blind, placebo-controlled, company-sponsored Phase III trial. Instead, the sBLA was based on an open-label study, known as E2100, conducted by the National Institutes of Health-affiliated Eastern Cooperative Oncology Group. In September 2006, the agency delivered a complete response letter asking Genentech to audit the E2100 data in the same manner expected of a company-sponsored trial. (See BioWorld Today, Sept. 12, 2006.)

Genentech did as the FDA asked, resubmitting the revised sBLA in August 2007. But a second setback occurred in December, when ODAC narrowly voted against approval. (See BioWorld Today, Dec. 6, 2007.)

E2100 had randomized 722 previously untreated breast cancer patients to receive Avastin plus paclitaxel chemotherapy or paclitaxel alone. The study met its primary endpoint of improving progression-free survival (PFS): patients receiving Avastin achieved a median PFS of 11.3 months compared to 5.8 months for the control arm. However, there was no statistically significant difference in median overall survival, with the Avastin group surviving 26.5 months and the control group surviving 24.8 months, leading ODAC to debate the clinical merits of PFS.

The panel also raised questions about the design of E2100 once again and voiced concerns about adverse events. Six deaths were found to be ‘definitely or probably’ caused by toxicity related to Avastin, and 71.1 percent of patients in the Avastin arm experienced severe adverse events, compared to 51 percent in the control arm.

But between ODAC’s negative decision and the FDA’s positive one, data from a new Phase III trial became available. Known as AVADO, the trial was sponsored by Roche and properly designed. The randomized, double-blind, placebo-controlled Phase III study compared Avastin plus docetaxel chemotherapy to placebo plus docetaxel in the first-line treatment of 736 patients with locally recurrent or metastatic HER2-negative breast cancer. Avastin was administered at 15 mg/kg or 7.5 mg/kg every three weeks, and both doses resulted in a statistically significant improvement in PFS. [PAL Ed.: But not in overall survival, as Breast Cancer Action also pointed out in the trial upon which the approval was formally based] (See BioWorld Today, Feb. 14, 2008.)

Although the AVADO data were not officially included in the Avastin sBLA, Genentech submitted them to the FDA for consideration. That may have helped to sway the agency’s decision to go ahead and grant accelerated approval.

In its news release, Genentech said that converting its accelerated approval into a full approval will be dependent on an FDA review of the full AVADO data as well as data from a Genentech-sponsored Phase III trial known as RIBBON I. Initial RIBBON I data are expected later this year, while overall survival data from AVADO are expected around mid-2009.Genentech also plans to provide the FDA with data from three additional randomized trials that are either ongoing or planned.

So the question remains: Will FDA’s approval of a new indication based on a trial that was a not traditional double-blind, placebo-controlled, company-sponsored Phase III trial pave the way for the loosening of standards on what data the FDA will accept for approvals? Does the FDA’s overruling of its own advisory committee make it likely that the FDA will ignore its advisory committee recommendations more often? And what does the FDA’s approval of a drug based on a secondary endpoint like progression-free survival when the drug failed to meet the primary endpoint of overall survival bode for the future?

Got thoughts on these questions? Post ‘em in the comments.

PAL coalition member Breast Cancer Action today lambasted the FDA’s decision to grant accelerated approval for Avastin® (bevacizumab), in combination with paclitaxel chemotherapy, for the treatment of patients who have not received chemotherapy for their metastatic HER2-negative breast cancer. Back in December, Breast Cancer Action had applauded an FDA Advisory Committee decision to recommend that the FDA not approve the drug for metastatic breast cancer. (See PAL member Breast Cancer Action declares victory as FDA denies approval for Avastin as a breast cancer treatment) The FDA normally follows the recommendations of its advisory committees, but of course is not required to.

Below is Breast Cancer Action’s press release on the issue. And here is Genentech’s press release on the approval.

PATIENTS LOSE, GENENTECH WINS WITH FDA’S AVASTIN RULING

San Francisco, CA ( February 22, 2008) —Breast Cancer Action (BCA) strongly disagrees with the Food and Drug Administration’s decision today giving accelerated approval to biotech company Genentech’s application to market its drug Avastin as a treatment for metastatic breast cancer at this time.

“The FDA has lowered the bar on the approval of breast cancer therapies. At a time when many questions are being raised about how the FDA approves drugs for market, today’s decision is a victory for drug companies, but not for patients,” BCA Executive Director Barbara A. Brenner said.

BCA has long opposed Genentech’s application, arguing that no evidence has been presented that shows Avastin improves overall survival or quality of life.

In its application to the FDA, Genentech said that a clinical trial indicated that Avastin prolongs progression-free survival. However, BCA argued – and continues to argue — that that endpoint is meaningless because (1) it does not address the patient’s quality of life during those additional months, a very real question because of some of the serious side effects a number of the women experienced, and (2) it has not been shown in this case to correlate with overall survival. The data from another trial done by Genentech’s parent, Roche, has not been released, but it appears that it has the same limitations.

Breast Cancer Action is a national watchdog and advocacy organization that carries the voices of people affected by breast cancer to inspire and compel the changes necessary to end the breast cancer epidemic.

One of my favorite organizations is Breast Cancer Action, which is also a member of the Prescription Access Litigation coalition. (See previous PAL blog posts about them here. They are the brilliant and creative people behind the Think Before You Pink campaign.)

The good folks at Breast Cancer Action have just published a guide to drug companies’ Patient Assistance Programs that offer free or discounted breast cancer drugs:

Many pharmaceutical companies offer Patient Assistance Programs to help cover the cost of treatment. To make this information more readily available, BCA has compiled and posted information about manufacturers’ Patient Assistance Programs for drugs commonly prescribed to breast cancer patients. Click on the brand, generic, or manufacturer name to learn more about the specific program. Please note that they have varying eligibility requirements, enrollment processes, and duration of assistance.

PAL coalition member Breast Cancer Action today issued a statement on the FDA’s denial of Genentech’s [NYSE:DNA] application to have its drug Avastin approved for treatment of metastatic breast cancer. Avastin is currently approved for treatment of metastatic colorectal cancer and advanced non-small cell lung cancer. Genentech has been in the news recently for restricting the availability of Avastin to pharmacies that divide vials of Avastin for use as a treatment for the eye condition macular degeneration. These “off label” uses of Avastin are much less expensive than Genentech’s drug Lucentis, which is approved for macular degeneration. Genentech also came under fire in 2006 for greatly increasing the price of Avastin, in what many saw as a preemptive move in anticipation of what Genentech hope would be FDA approvals for lung cancer and breast cancer. The FDA did approve the drug for advanced non-small cell lung cancer.

Here is Breast Cancer Action’s statement on the Avastin denial:

Breast Cancer Action (BCA) applauds yesterday’s recommendation by a Food & Drug Administration (FDA) advisory committee to deny approval of Avastin as a breast cancer drug for metastatic patients.

In a letter to the Oncologic Drugs Advisory Committee (ODAC), BCA urged denial based on the fact that the drug’s maker, biotech giant Genentech, did not provide data indicating that Avastin improved overall survival or quality of life.

By a 5-4 vote, the committee agreed, indicating that the toxic side effects outweighed the potential benefits of the drug. ODAC member and patient advocate Natalie Compagni Portis told the New York Times that she voted no because while it’s painfully true that metastatic breast cancer isn’t curable, “I don’t think that means that we should just say, ‘Well, here, try this,’ if there isn’t meaningful data to support it.”

BCA Executive Director Barbara A. Brenner told the San Francisco Chronicle, “It’s not necessarily a bad drug. We just don’t know if it’s a good drug.” Brenner also criticized the estimated $100,000 a year price tag for Avastin.

BCA believes that a drug should increase overall survival or improve quality of life before being approved. Additionally, it should be more affordable than the available alternatives.

The recommendation now goes to the FDA commissioner, who will make a decision in February. We will continue taking action–and asking you to do so–on the issue, so stay tuned.

PAL member Breast Cancer Action announced today its 6th Annual Think Before You Pink campaign. This campaign has tirelessly worked to urge consumers to ask critical questions about the hundreds of pink ribbon products and promotions that are marketed every October in honor of Breast Cancer Awareness Month (BCA calls it Breast Cancer Industry Month). This year’s campaign focuses on “pinkwashing” — the practice of companies that increase sales by putting pink ribbons on their products, even though these products contribute to the breast cancer epidemic.

Here’s the press release. We wish Think Before You Pink the best of luck.

FOR IMMEDIATE RELEASE

Contact:
Mary DeLucco
mdelucco@bcaction.org
415.243.9301 xt 16
Katrina Kahl
kkahl@bcaction.org
415.243.9301 xt 19

Breast Cancer Action Launches 6th Year of Think Before You Pink
San Francisco, CA — (October 1, 2007) — Breast Cancer Action (BCA) today launched its annual Think Before You Pink campaign with a new focus — “pinkwashing” companies that increase sales by putting pink ribbons on their products, even though these products contribute to the breast cancer epidemic.

Since its inception in 2002, BCA’s Think Before You Pink campaign (www.thinkbeforeyoupink.org) has been urging consumers to ask critical questions about the hundreds of pink ribbon products and promotions that are marketed every October in honor of Breast Cancer Awareness Month (BCA calls it Breast Cancer Industry Month). Calling for transparency and accountability from companies that use pink ribbons to sell products, BCA believes that consumers can and should ask questions about how the money is being raised and where the money is going.

The big question of the campaign this year is which companies are engaging in pink ribbon marketing while manufacturing products that are contributing to the epidemic. Toward this end, BCA is singling out the car, dairy, and cosmetics industries.

“These pinkwashing companies are trying to have it both ways,” says BCA Executive Director Barbara A. Brenner. “If they care as deeply as they say they do about women’s lives, they’ll clean up their products.”

For example, Ford, Mercedes, and BMW are each raising funds with campaigns that urge consumers to buy and drive cars for breast cancer awareness and research. However, car exhaust contains toxic chemicals that are linked to the disease, and by urging consumers to buy and drive polluting cars in the name of breast cancer, they are also encouraging consumers to unwittingly help increase the incidence of the disease.

“We’re not telling anyone not to buy these products or not to drive,” says Brenner. “We’re asking that consumers think before they buy, contact the companies to demand cleaner products, and remember that they have options. That’s why it’s called ‘Think Before You Pink’.”

The Think Before You Pink web site, www.thinkbeforeyoupink.org, features an updated “Parade of Pink,” a list of some of the hundreds of pink ribbon products and promotions on the market, as well as a list of the six critical questions consumers can ask before buying a pink ribbon-wrapped product.

PAL member Breast Cancer Action issued the following statement yesterday. This raises some important issues — about the use of prescription drugs to prevent cancer, about the environmental vs. individual factors in disease, and about how to deal with serious illnesses like cancer — especially whether to emphasize prevention vs. treatment, and even within prevention, whether to address individual prevention measures vs. social/epidemiological prevention measures.

July 24, 2007 (San Francisco)-Breast Cancer Action (BCA) opposes today’s recommendation by a U.S. Food and Drug Administration (FDA) advisory panel to approve the use of raloxifene (tradename Evista) to reduce the risk of breast cancer in postmenopausal women who do not have breast cancer but are considered at high risk for developing the disease.

In December 2005, raloxifene’s manufacturer, Eli Lilly, paid a fine of $36 million for illegally promoting the drug to doctors as a breast cancer “preventative.” Now, the company is one step closer to getting FDA approval to market the drug to reduce the risk of breast cancer in women deemed at high risk, despite the fact that the drug increases the risk of serious-and potentially fatal-side effects.

BCA has long opposed a pills-based approach to breast cancer prevention, believing that any pill powerful enough to prevent breast cancer will most certainly cause another disease.

“The relatively few number of women who may avoid breast cancer by taking raloxifene is far outweighed by the risk of blood clots and strokes from the drug that they and thousands of other women will experience,” says BCA Executive Director Barbara A. Brenner.

“If Eli Lilly is permitted to market raloxifene, many women will consider taking it because most women overestimate their risk of breast cancer,”
Brenner says.

Tamoxifen, the only other drug that the FDA has approved to reduce the risk of breast cancer, has not sold well for this purpose because most women are not willing to take a drug with such serious side effects. Raloxifene was tested against tamoxifen, and the data from that study showed very little difference in the side effects of the two drugs.

BCA strongly urges FDA Commissioner Andrew von Eschenbach to seriously consider the views of the FDA scientists and committee members who opposed approval, and oppose today’s recommendation.

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Breast Cancer Action (www.bcaction.org) is a non-profit education and advocacy organization that does not accept funding from pharmaceutical companies or any other organizations that profit from or contribute to the breast cancer epidemic.

This just in from Breast Cancer Action, a member of Prescription Access Litigation’s coalition of 130+ consumer advocacy organizations. The pricing of cancer drugs is one of the most troubling trends in the world of prescription drugs. This press release points out that the price today of these drugs is what’s important, not some arbitrary notion of “effective cost,” which seems more like an actuarial notion than a principle that should guide patients’ and doctors’ choices regarding medications.

FOR IMMEDIATE RELEASE

Mary DeLucco
mdelucco@bcaction.org
415-243-9301, ext. 16

Breast Cancer Action Says Two New Drug Pricing Studies Miss the Mark

San Francisco, CA (June 26, 2007) — Breast Cancer Action (BCA) today expressed grave concerns about two new studies that purport to justify the exorbitantly high price of breast cancer drugs.

One of the studies looked at Herceptin –a drug that costs upwards of $40,000 a year. The other study looked at Aromasin – an aromatase inhibitor that costs more than $3000 per year in the United States.

Both studies measured “cost effectiveness” in terms of the number of years each drug prolonged life, combined with the quality of life. This “cost effectiveness” measure was used to estimate the cost of the drugs over a patient’s lifetime. Based on this equation, researchers said the “effective” cost of the drugs was much less than the actual purchase price.

But BCA says that the “effective” cost is a meaningless concept to individual breast cancer patients, and points out that both studies were funded and — in the case of the Herceptin study partially staffed — by the companies that make the drugs.

“The bottom line is that Herceptin still costs at least $40,000 a year in the United States,” says BCA Executive Director Barbara A. Brenner. “The cost of these cancer drugs will not be reduced to reflect the ‘effective cost’ detailed in these studies. The ‘projected lifetime costs’ are meaningless to patients who have to pay for these drugs today.”

Brenner also points out that studies like these will prove most useful for pharmaceutical companies by encouraging insurance firms to pay the very high prices the drug companies are charging.

The fact that these drugs cost thousands of dollars is more evidence of the need for the United States to work toward a universal health care system that would allow the government to negotiate with pharmaceutical companies for lower drug prices.

Breast Cancer Action (www. bcaction.org) is a national grassroots education and advocacy organization that carries the voices of people affected by breast cancer to inspire and compel the changes necessary to end the breast cancer epidemic.

Since 1998, BCA has refused to accept funds from corporations that may create a real or apparent conflict of interest for BCA. Corporations covered by this policy include pharmaceutical companies.

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