Avastin/Lucentis Update 24: Dispute Between FDA and Genentech
This commentary was just posted on the WSJ Health Blog.
June 17, 2008, 4:11 pm
FDA Contradicts Genentech on Eye Drug
Posted by Jacob Goldstein
WSJ Health Blog
An FDA letter to Senate investigators appears to contradict one of Genentech's main reasons for restricting the distribution of its cancer drug Avastin.
Last year, the company said it would no longer sell the drug to compounding pharmacies, which repackage Avastin for use in patients with eye disease. In an open letter, the company said it was making the switch in part because of FDA inspectors' concerns that some batches of the drug didn't meet standards for use in the eye.
"In order to resolve the concerns raised by the FDA, we destroyed four batches of Avastin deemed unsuitable for use in the eye," the letter said. The letter added: "These lots would have been entirely suitable for its approved use as an intravenous cancer medication."
But the FDA says its inspectors "identified deficient practices and the lack of effective processes to know what was in those four lots. Consequently, the Agency recommended that those lots should be considered unfit for use for any indication."
That statement comes in a letter the agency sent in response to questions from Sen. Herb Kohl (D-Wisc.), chairman of the Senate Special Committee on Aging.
Genentech also sells Lucentis, a drug that is similar to Avastin and that has been approved for an eye disease called wet age-related macular degeneration. A dose of Lucentis for the disease costs roughly $2,000; a comparable dose of Avastin costs about $50.
"There's no doubt that Genentech's scientific and medical innovation has produced life-saving cancer drugs and pioneering eye disease treatments," Kohl said in an email to the Health Blog. "But the rising costs to Medicare, which in this case may be in the billions of dollars, is our focus."
Lucentis has about half of the market for treating macular degeneration; Avastin has "the vast majority" of the other half, David Williams, president-elect of the American Society of Retina Specialists, told the Health Blog.
A central issue in the FDA inspection was the company's method for detecting microscopic levels of "glass particulates" in the lots, according to an internal memo by Kohl's staff.
"Genentech has found a way to blame FDA for their decision to limit their distribution of Avastin," a "high-level FDA eye expert" wrote in an agency email quoted by the memo. "The manufacturing problem at their facility that resulted in glass in their product would be an issue for either the on label oncology indications or the off label ophthalmology indications."
Genentech disputes that assertion. "It is our belief that those four lots were suitable for use in their approved indications," Krysta Pellegrino, a company spokeswoman, told the Health Blog.
Other factors also contributed to Genentech's decision to change the distribution. The company has cited a warning letter the FDA sent last year to compounding pharmacy that was repackaging Avastin for use in the eye. And, Pellegrino said, contracts with compounding pharmacies were set up before Lucentis was on the market. "We believe that Lucentis is the most appropriate treatment for patients with wet AMD," she said.
The company has made that case to the FDA as well. In 2006, the year Lucentis was approved, Genentech "approached FDA . to change the Avastin labeling to explicitly state Avastin is not intended for opthalmologic use," according an internal FDA email obtained by Senate investigators. But FDA "felt at that time that there was no safety-related basis adequately justifying that labeling change," according to the email.
The language was never added to the drug's label.
Sales of Lucentis, once projected to top $1 billion, appear to have peaked well short of that. In the first quarter of this year, the company sold $198 million worth of the drug, down 6% from the year-earlier period, as the drug's market share for newly diagnosed patients fell to 40% from 55%.
Eye doctors say they've grown comfortable using Avastin in the eye, despite the fact that it hasn't been approved for that use. And a compromise solution worked out between Genentech and doctors' groups means that doctors can buy Avastin from wholesalers and have it repackaged by compounding pharmacies. The logistics of this can get a bit complicated, but Williams said he hadn't heard of any eye patients being unable to get Avastin.
Some pharmacies may still be using Avastin they stockpiled before the new policy came into place on Jan. 1, Williams added. "Problems could potentially become manifest in the coming weeks or months," as those stockpiles dwindle, he said.
Meanwhile, the NIH is running a big head-to-head study comparing the use of the drugs in the eye. Last year, a Genentech official emailed the researchers to say the board supported the research and the company would provide Lucentis and Avastin for the study, according to the Senate memo. But the company ultimately chose not to do so. "Any documentation from a Genentech employee stating that the board of directors committed to participate is incorrect," Pellegrino said.
The study started enrolling patients earlier this year. The government is paying for all of the Lucentis and Avastin, at a cost of about $25 million.
FDA Contradicts Genentech on Eye Drug
Posted by Jacob Goldstein
WSJ Health Blog
An FDA letter to Senate investigators appears to contradict one of Genentech's main reasons for restricting the distribution of its cancer drug Avastin.
Last year, the company said it would no longer sell the drug to compounding pharmacies, which repackage Avastin for use in patients with eye disease. In an open letter, the company said it was making the switch in part because of FDA inspectors' concerns that some batches of the drug didn't meet standards for use in the eye.
"In order to resolve the concerns raised by the FDA, we destroyed four batches of Avastin deemed unsuitable for use in the eye," the letter said. The letter added: "These lots would have been entirely suitable for its approved use as an intravenous cancer medication."
But the FDA says its inspectors "identified deficient practices and the lack of effective processes to know what was in those four lots. Consequently, the Agency recommended that those lots should be considered unfit for use for any indication."
That statement comes in a letter the agency sent in response to questions from Sen. Herb Kohl (D-Wisc.), chairman of the Senate Special Committee on Aging.
Genentech also sells Lucentis, a drug that is similar to Avastin and that has been approved for an eye disease called wet age-related macular degeneration. A dose of Lucentis for the disease costs roughly $2,000; a comparable dose of Avastin costs about $50.
"There's no doubt that Genentech's scientific and medical innovation has produced life-saving cancer drugs and pioneering eye disease treatments," Kohl said in an email to the Health Blog. "But the rising costs to Medicare, which in this case may be in the billions of dollars, is our focus."
Lucentis has about half of the market for treating macular degeneration; Avastin has "the vast majority" of the other half, David Williams, president-elect of the American Society of Retina Specialists, told the Health Blog.
A central issue in the FDA inspection was the company's method for detecting microscopic levels of "glass particulates" in the lots, according to an internal memo by Kohl's staff.
"Genentech has found a way to blame FDA for their decision to limit their distribution of Avastin," a "high-level FDA eye expert" wrote in an agency email quoted by the memo. "The manufacturing problem at their facility that resulted in glass in their product would be an issue for either the on label oncology indications or the off label ophthalmology indications."
Genentech disputes that assertion. "It is our belief that those four lots were suitable for use in their approved indications," Krysta Pellegrino, a company spokeswoman, told the Health Blog.
Other factors also contributed to Genentech's decision to change the distribution. The company has cited a warning letter the FDA sent last year to compounding pharmacy that was repackaging Avastin for use in the eye. And, Pellegrino said, contracts with compounding pharmacies were set up before Lucentis was on the market. "We believe that Lucentis is the most appropriate treatment for patients with wet AMD," she said.
The company has made that case to the FDA as well. In 2006, the year Lucentis was approved, Genentech "approached FDA . to change the Avastin labeling to explicitly state Avastin is not intended for opthalmologic use," according an internal FDA email obtained by Senate investigators. But FDA "felt at that time that there was no safety-related basis adequately justifying that labeling change," according to the email.
The language was never added to the drug's label.
Sales of Lucentis, once projected to top $1 billion, appear to have peaked well short of that. In the first quarter of this year, the company sold $198 million worth of the drug, down 6% from the year-earlier period, as the drug's market share for newly diagnosed patients fell to 40% from 55%.
Eye doctors say they've grown comfortable using Avastin in the eye, despite the fact that it hasn't been approved for that use. And a compromise solution worked out between Genentech and doctors' groups means that doctors can buy Avastin from wholesalers and have it repackaged by compounding pharmacies. The logistics of this can get a bit complicated, but Williams said he hadn't heard of any eye patients being unable to get Avastin.
Some pharmacies may still be using Avastin they stockpiled before the new policy came into place on Jan. 1, Williams added. "Problems could potentially become manifest in the coming weeks or months," as those stockpiles dwindle, he said.
Meanwhile, the NIH is running a big head-to-head study comparing the use of the drugs in the eye. Last year, a Genentech official emailed the researchers to say the board supported the research and the company would provide Lucentis and Avastin for the study, according to the Senate memo. But the company ultimately chose not to do so. "Any documentation from a Genentech employee stating that the board of directors committed to participate is incorrect," Pellegrino said.
The study started enrolling patients earlier this year. The government is paying for all of the Lucentis and Avastin, at a cost of about $25 million.
posted by Irv Arons @ 4:46 PM
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