CATT Study Update 3 Avastin vs Lucentis – To Get Underway by Year’s End!

The following information was provided to me from the recent CATT Study training meeting held in Philadelphia.

(Please note the addended updates below.)

Patient enrollment for the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT Study) is set to begin before the end of the year, with enlistment beginning on December 1st.

The study will enroll about 1,200 patients with newly diagnosed wet AMD, randomly assigned to one of four treatment groups:

(Group1) Lucentis with four-week dosing, and after one year, re-randomization to Lucentis every four weeks or variable dosing as required based on diagnostic findings;

(Group 2) Avastin with four-week dosing, and after one year, re-randomization to Avastin every four weeks or variable dosing as required based on diagnostic findings;

(Group 3) Lucentis on a variable dosing schedule for 2 years; after initial treatment, with monthly evaluation and re-treatment based on signs of lesion activity; and

(Group 4) Avastin on a variable dosing schedule for 2 years; after initial treatment, with monthly evaluation and re-treatment based on signs of lesion activity.

The regimens are based upon the fact that Avastin is generally given on a variable basis and Lucentis has only been formally tested in a fixed regimen. The main objective will be changes in visual acuity, with secondary objectives including change in lesion size, fluid found in optical coherence tomography and cost, which the study chairman, Dr. Dan Martin of Emory University emphasized is not the sole purpose of the study.

The study will follow patients for two years and will take about four years to complete. One year follow-up data will be reported in late 2009. The study will be conducted in 47 centers in the US.

NEI/NIH is emphasizing that this is more than just a cost study, and that the primary goals are to better understand the safety and efficacy of intravitreal Avastin and to develop better dosing/re-treatment guidelines for both Avastin and Lucentis.

The Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) is a set of multicenter, randomized clinical trials of treatments for neovascular age-related macular degeneration (AMD), the leading cause of blindness in the United States. The Lucentis-Avastin comparison trial is supported by the National Eye Institute (NEI) of the National Institute of Health (NIH).

I expect to have a list of participating centers, hopefully with contact information, by the end of this week and will attempt to put it online. If it becomes available from the University of Pennsylvania website, I will link to that source.

Update:

I now have the CATT clinical site information on 46 of the 47 sites that are believed to be interested in participating in the clinical trial. I have been asked not to publish the names until the contracts with Upenn have been signed. I plan to honor that request.

However, anyone wishing to know the names of the clinics in their state that will be recruiting patients for the study can email me (iarons(at)erols.com – or the link at the side of this page) and I will be happy to cut and paste and supply you with the names of local clinics. Just mention the state that you are interested in.

As soon as Upenn gives me the OK, I will publish the information – or link to their site if they put it online.

I have also learned, as of 10/20/07, that the CATT Study will not be effected by the recent decision by Genentech to cut off the supply of Avastin to compounding pharmacies.

UPenn will act as the compounding pharmacy and will supply the doses of Avastin needed for the study to the 47 participating clinics.

Avastin Lucentis Update 15 The Brits Join in on the Fight

Apparently, British doctors are joining the fight against the high price of Lucentis and have called for a comparative study with Avastin, similar to the one about to begin in the U.S., funded by NEI/NIH. I just came across this newspaper article written a little over a month ago in The Guardian.

Please see the addendum added at the end of this article for an important update.


NHS doctors challenge high drugs prices

Sarah Boseley, health editor, The Guardian
Monday July 30, 2007

British doctors are to rebel against high prices set by pharmaceutical companies for their products by giving patients a cheap but unlicensed drug that prevents blindness, the Guardian has learned.

Unable to afford to treat all those losing their sight with a licensed and extremely expensive drug, Lucentis, some primary care trusts are giving NHS doctors the green light to use tiny shots of a similar drug, Avastin, which is marketed for bowel cancer, but costs a fraction of the price. Avastin is widely used for eye complaints in the United States.

A call from the former health secretary, Patricia Hewitt, for Avastin's manufacturer to put the drug through trials for wet age-related macular degeneration went unheeded. Now the NHS is funding a groundbreaking trial which will compare Avastin directly with Lucentis. Both drugs are manufactured by Genentech.

The moves represent the first real challenge in this country to high prices set by drug companies. There is growing unease at the cost of new drugs and high prices have led to the banning or rationing of some medicines in the NHS by the National Institute for Health and Clinical Excellence (Nice). The companies say they need billions of dollars in sales to recoup their research and development costs, but critics accuse them of profiteering.

Meanwhile, in the developing world, unaffordably high drug prices have brought the pharmaceutical industry into disrepute, forced their prices down and led to successful campaigns to allow generic copycat companies to sell cheap versions of drugs.

Around 26,000 people develop wet age-related macular degeneration (AMD) every year - a condition that can make them blind within months. Lucentis can save and even improve their vision - but Genentech, the manufacturers, and Novartis, who market it in the UK, have set the price so high - at £761.20 per injection - that Nice has said it should only be used in the 20% worst cases and then only when patients have already lost the sight of one eye.

Appalled at the implications, a number of ophthalmic surgeons in the UK are now offering treatment with Avastin, a very similar but bigger molecule also made by Genentech but licensed for bowel cancer. One bowel cancer phial can be split into many tiny doses suitable for injection into the eyes, costing as little as £10 a shot. In spite of the absence of trials or a licence, the use of Avastin has spread through the US and there is now data on more than 7,000 patients. It has also been used by some private clinics in the UK.

In the Greater Manchester area, public health directors of PCTs have taken the unprecedented decision to offer patients Avastin on the NHS. "We think as many people as possible should be treated for wet AMD. To afford it we need to use Avastin," said Peter Elton, director of public health for Bury, who is leading on the issue for the Greater Manchester area. "If you have only got one eye affected, the other eye might get something else the next year. By the time you come to treat the wet eye, it has gone too far. We think that is not ethically acceptable."

He and his colleagues are happy with the evidence amassed so far and he points out that Medicare, the state-funded healthcare service in the US, is using Avastin in 48 out of 50 states.

Moorfields eye hospital in London, the most famous in the country, is also exploring a scheme to use Avastin on the NHS. But the stakes are so high for the NHS that it is taking the unprecedented step of funding a trial which will directly compare the use of Avastin and Lucentis in wet AMD.


Further investigation has uncovered an additional information source on this story. PharmaTimes World News has published the “story behind the story”, providing further background about the reasons behind the push by British ophthalmologists to avoid the use of Lucentis and push for the approval to use Avastin in treating their AMD patients. For the complete story, follow this link.

Avastin Lucentis Update 17 The Controversy Heats Up Once Again

This writeup was posted on the WSJ Health Blog earlier this afternoon. Isn’t it interesting about the timing – just as the CATT Study comparing the two drugs is set to begin the day after Genentech cuts off supply of Avastin to compounding pharmacies.

Genentech Restricting Avastin Sales To Curb Eye Use

Posted by Jacob Goldstein
WSJ Health Blog
October 11, 2007, 2:39 pm

The toughest competitor for Genentech’s eye drug Lucentis has been Avastin, a Genentech cancer drug.

Today, though, Genentech said it wouldn’t let wholesalers sell Avastin to compounding pharmacies, which have been taking Avastin out of vials and putting it into pre-packaged syringes for eye treatment.

Avastin isn’t approved for use in the eyes, but it’s very similar to Lucentis, which the FDA cleared last year to treat an eye disease called wet macular degeneration. Some doctors substitute Avastin for Lucentis because a dose of the cancer medicine used for the eye disease is a lot cheaper. Avastin used that way costs about $40 a month compared with $2,000 a month for Lucentis. (Physicians are free to prescribe drugs for unapproved uses.)

In a letter explaining the decision (see below), Genentech pointed out that Lucentis was developed expressly for use in the eyes, and that the FDA has expressed safety concerns over the re-packaging of Avastin.

In the first six months of this year, U.S. sales of Avastin were $1.1 billion, and Lucentis sales were $420 million.

Avastin, which is sold through wholesalers, will still be available to hospital pharmacies and directly to doctors after the company ends sales to compounding pharmacies at the end of next month.

But Anne Fung, a San Francisco ophthalmologist, said she worries that some doctors, unable to buy the drug from compounding pharmacies, may do the re-packaging work themselves without the proper safety equipment. “This move is taking it out of a regulated environment into an unregulated environment,” she told the Health Blog. That could increase the risk of contamination and serious eye infections.

Fung, who said Avastin and Lucentis are split roughly 50-50 among macular degeneration patients, said she would likely try to get Avastin from a hospital pharmacy, which might charge her more than the compounding pharmacy.

Genentech spokeswoman Dawn Kalmar pointed out that most wet macular degeneration patients are covered by Medicare, and said the company helps connect patients who can’t cover their copay (which can be $400 a month for Lucentis) with charities that help with payment.


Here is a copy of the Genentech letter:


Letter to Physicians

October 11th, 2007

Dear Retinal Community Member:

On behalf of Genentech, manufacturer of Avastin® (bevacizumab), I am writing to inform you of a change to the distribution of this product. Like all of Genentech's FDA-approved oncology products, Avastin is distributed directly to physicians and hospital pharmacies through authorized wholesale distributors. Genentech has also permitted compounding pharmacies to purchase Avastin from authorized wholesale distributors. As of November 30, 2007, Genentech will no longer allow compounding pharmacies to purchase this product directly from wholesale distributors. This change does not otherwise impact the distribution of Avastin nor will it remove Avastin from the marketplace or otherwise limit a physician's prescribing choice. Physicians can still order Avastin directly from authorized wholesale distributors.

Avastin is an infused medication approved by the U.S. Food and Drug Administration (FDA) for use in combination with intravenous 5-fluorouracil-based chemotherapy for first- or second-line treatment of patients with metastatic carcinoma of the colon or rectum and in combination with carboplatin and paclitaxel for the first-line treatment of patients with unresectable, locally advanced, recurrent or metastatic non-squamous non-small cell lung cancer (NSCLC).

Despite the availability of LUCENTIS® (ranibizumab injection), an FDA-approved treatment for neovascular (wet) age-related macular degeneration (AMD), some ophthalmologists are using Avastin for the unapproved treatment of this and other ocular indications. Avastin is not FDA-approved for ocular uses and is not manufactured to meet U.S. Pharmacopoeia (USP) ophthalmic standards. This change will not go into effect until November 30, 2007 to allow for physicians and compounding pharmacies to adjust to this change in distribution.

A series of events have contributed to our decision to make this change to our distribution of Avastin. Most important among these events is the FDA approval and broad availability of Lucentis for patients with wet AMD. Subsequent to the approval of Lucentis, the FDA raised concerns related to the sterility and repackaging of Avastin for ocular use in a Warning Letter to a compounding pharmacy and, separately, during a routine FDA inspection of our South San Francisco manufacturing facility, concerns were raised by inspectors related to the ongoing ocular use of Avastin because it is not designed, manufactured or approved for this use. In addition, we note that Avastin has not undergone any formal, randomized, controlled clinical trials for ocular use.

We recognize this change may require some adjustment on your part and are acknowledging this by notifying you seven weeks prior to the change taking effect. In addition, I would like to reiterate Genentech's commitment to patient access to our approved products. We have always believed that no eligible patient should go without one of our approved medicines due to financial barriers alone. As such, we have invested in a dedicated support services organization to assist with providing patients access to our medicines. Specific to Lucentis, we offer The LUCENTIS Commitment™, a comprehensive support program dedicated to facilitating timely reimbursement. If you or your patients have any questions related to our access and reimbursement services, please contact us toll-free at 1-866-724-9394.

Should you have questions or comments about this distribution change, I encourage you to contact us at physicianquestions@gene.com. We will do our best to respond to your inquiry by the end of the next business day. Thank you for your patience and understanding as we move forward with implementing this change.

Sincerely,

Susan Desmond-Hellmann, M.D.,M.P.H.
President, Product Development
Genentech, Inc.