Archive for the ‘Drug Development’ Category

Genentech this week will step up its efforts to keep the drug Avastin available as a treatment for breast cancer, urging the Food and Drug Administration to give it one more chance to prove the medicine works.

At a hearing on Tuesday and Wednesday in suburban Washington, Genentech will ask the F.D.A. to reconsider its proposal last December to revoke the approval of Avastin for breast cancer on the grounds that new studies did not confirm that the drug helped patients.

Genentech’s approach seems intended to broaden the terms under which Avastin can remain available. The company is arguing that even if the F.D.A. reaffirms that data do not support Avastin’s effectiveness, the approval should be retained while Genentech does one more clinical trial. Avastin has remained available for breast cancer pending the appeal process.

Avastin was put on the market under an accelerated program begun in the early 1990s that allows drugs for serious diseases to be approved with less than the usual amount of evidence, subject to further studies. Dozens of drugs have been approved this way, and in at least a couple of cases approvals have been withdrawn. But this is the first time the F.D.A. will hold a hearing to consider a company’s appeal.

The debate over Avastin has evoked passions on both sides among those involved in women’s health issues. Some patient advocates argue that the F.D.A. needs to revoke the approval to maintain the integrity of the accelerated process and to ensure that cancer patients receive drugs that work.

But some breast cancer patients are expected to testify at the hearing that the drug should be kept available because it helps some women, even if not all.

“It’s so depressing to think that a federal agency can make a decision that can potentially cause me to die,” said Crystal Hanna, 35, a mother of two from Parkersburg, W.Va., who said Avastin has kept her cancer under control for almost a year.

The public comments sent to the F.D.A. before the hearing at its campus outside Washington, overwhelmingly support retaining the approval. Many of them, using virtually identical language, cite the case of Ms. Hanna, who drafted a comment for friends that circulated widely on the Internet.

Even if approval as a breast cancer treatment is ultimately rescinded, Avastin will retain approval to treat lung, colon, kidney and brain cancers. So doctors will be able to use it “off label” to treat breast cancer. But insurers might no longer pay for it for that use, putting the drug, which can cost $88,000 a year, out of reach for many women.

The Avastin issue has become caught up in the politics of overhauling health care, with some critics saying the decision not to pay for it represents rationing and others saying that Medicare should not pay for a drug that does not work. The F.D.A. maintains that it is not permitted to consider costs.

The ultimate decision will be made by the F.D.A. commissioner, Dr. Margaret A. Hamburg, who appears to have some latitude. The rules say that the F.D.A. “may” revoke the approval of a drug, but does not have to.

“Even where F.D.A. determines that confirmatory trials do not establish clinical benefit, withdrawal is not required and instead should be based on the public health considerations that motivate the accelerated approval statute,” Genentech argues in a summary of its arguments filed before the hearing.

But the F.D.A.’s drug division views the company’s request as a stalling tactic. “How many bites of the apple do you get?” Dr. Richard Pazdur, the director of the agency’s oncology drug division, said in an interview at a cancer conference early this month.

The agency, in a summary of its arguments, says that because it has already determined that the benefits of Avastin do not outweigh the risks, retaining the approval while the new study is conducted “would not be in the interest of the public health and would jeopardize the integrity of the accelerated approval program.”

Genentech and its parent company, Roche, could lose as much as $1 billion in annual sales if the breast cancer approval were revoked. Already Avastin sales for treatment of breast cancer have started declining. The drug is the world’s best-selling cancer drug, with sales last year of roughly $7 billion.

The F.D.A. approved the drug for advanced breast cancer in February 2008, after one clinical trial showed that combining Avastin with another drug, paclitaxel, delayed the median time before tumors worsened by 5.5 months, compared with using paclitaxel alone. But the women who got Avastin did not live significantly longer than those who got only paclitaxel, which is also known by the brand name Taxol.

Subsequent trials, in which Avastin was combined with different chemotherapy drugs, showed a much smaller delay in tumor progression, ranging from less than 1 month to 2.9 months. And again there was no improvement in survival for those receiving Avastin.

Based on those results and on the fact that Avastin has some life-threatening side effects, including bowel perforation and hemorrhaging, the F.D.A.’s cancer drug advisory committee voted 12 to 1 last July that the approval for the treatment of breast cancer be revoked.

The hearing this week will be before the same committee, which will make recommendations to the F.D.A. commissioner. Of the six voting committee members expected to attend, five voted to revoke the approval last July. The sixth was not at that earlier meeting. Since the data have not changed, Genentech, in the summary of its arguments, concedes it is not likely to change the committee’s mind about the benefits of Avastin.

Instead it will argue that the drug with which Avastin is combined matters. Therefore, the company should be given a chance to do another trial in which Avastin is combined with paclitaxel, as in the original trial that led to the drug’s approval.

Source: http://www.nytimes.com/2011/06/27/health/27drug.html