Tuesday, June 17, 2008

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.


5 Comments:

At 6:28 PM, Anonymous Felix said...

Hello Mr. Aron,

I just recently found your blog while working on a project comparing Avastin to Lucentis. I had some specific questions and if you are able I would love to speak with you. it would only take abot 5 minutes.
Please let me know if you are available.

Thank you for all your hard work.

Felix

 
At 10:33 PM, Blogger Irv Arons said...

Felix,

I prefer to respond to your questions via email. My email contact information is posted on the blog.

Irv Arons

 
At 2:54 AM, Anonymous Geoffrey W. Rutledge, MD, PhD said...

Hi,
I think your blog is terrific, and I would like to feature you on Wellsphere (http://www.wellsphere.com). Would you drop me an email?
Good health!
Geoff
--
Geoffrey W. Rutledge, MD, PhD
http://medblog.wellsphere.com

 
At 10:25 AM, Blogger bhola said...

Hello Mr. Aron

My mother's Optical Coherence Tomography states that:

Left Eye: Hyper-reflective areas with back scattering are seen below the neuronal layer and along the RPE-Choroid Complex suggestive of Sub-retinal Precipitates.

The RPE layer lying beneath the fovea shows increased backscattering with focal clumping and thickening suggestive of Drusen.

Hypo-reflective areas are seen between the outer neuronal and pigment epithelial layer suggests Serous Fluid.

There is thickening and irregularities of the RPE choroid complex para-foveally.
There is irregular reflectivity with back-scattering of echoes suggestive of ? CNVM Pattern (occult).


Now the doctor told us that there are only two types of medicines that can be used is Avastin or Lucentis. I have to inform within next 24 hours which one I would prefer. Being a layman in this subject, I am seeking your suggestion, which one I sould use for this treatment? I am also interested to know how long I have to keep my mother under treatment and what precautions I have to take during treatment. Last but not the least, what is the chance of curing of my mother.
(This is also to inform you that this left eye was operated before five months for cataract).

I am seeking your suggestion. Please help us with your opinion as soon as possible.

regards
Anindya

 
At 11:34 AM, Blogger Irv Arons said...

Anindya,

I am not a doctor and cannot give you the advice you need. That would have to come from your mother's doctor.

I only report on the work of others studying the two drugs. From what I have read, and until the CATT Study proves otherwise, both drugs appear to provide equivalent action against the wet form of AMD.

You might want to check out the MD Forum, part of the Delphi Forums, at this link:

http://forums.delphiforums.com/MDforum/messages

The doctor that runs the forum, and the members that write in all discuss AMD with some authority.

Good luck,

Irv Arons

 

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