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 16: And Now the Germans Join the Battle

I came across a story in a publication called APM Health Europe that states that several health insurers in Germany have decided to run clinical trials comparing Avastin to Lucentis for wet AMD. Apparently, the word is spreading that Avastin probably can do what Lucentis claims to do, but at a fraction of the cost!

The following is re-printed with permission of the publisher.

German health insurers launch study to compare Avastin to Lucentis in AMD
by Arjen Peters, APM Health Europe

BERLIN, Sept 19 (APM) – Several obligatory scheme health insurers in Germany have launched an evaluation of Roche's cancer drug Avastin (bevacizumab) in the treatment of wet-form age-related macular degeneration (AMD).

The objective is to compare the clinical efficacy but also the satisfaction of patients treated with Avastin in comparison to Novartis's Lucentis (ranibizumab), Eva Hansmann, head of the German federation of surgical ophthalmologists (BDOC), told APM.

Eventually, when the data collected has been evaluated, the German Federal Healthcare Committee (G-BA) will decide whether the off-label use of Avastin in AMD can become a service provided by the health insurance obligatory scheme, she added.

The initiative was taken at the beginning of May by the three health insurers Barmer, DAK and IKK Nordrhein in cooperation with the BDOC and the association of surgical ophthalmologists in North Rhineland (VOA Nordrhein).

Between times, other health insurers have manifested their interest in the project.

Each patient who is eligible for a treatment is informed on the current situation: three compounds equivalent from a therapeutic point of view but with annual costs of 14,100 euros for Lucentis, 9,350 euros for Macugen (pegaptanib) from Pfizer and 650 euros for Avastin.

"The three treatments are reimbursed. It is up to the patient to choose. We ask them to sign a consent form because of it being a study," a spokesperson for Barmer health insurers told APM.

NOVARTIS LEGAL CASE REJECTED

A legal case from Novartis to obtain an interim ruling for the immediate discontinuation of the study was rejected at the end of August by the Social Court in Düsseldorf.

The initiative does not have disproportionate disadvantages for the company and does not constitute anti-competitive practices but, on the contrary, increases the doctor's freedom of treatment and the patient's freedom of choice, the judges considered.

The health insurers' effort to sensitise the insurees to costs is considered in the verdict as being of "superior public interest" which is aimed at controlling health expenditure.

Novartis however remains confident about the outcome of the case, when it is treated on the merits.

"The Düsseldorf verdict is in complete contradiction with a previous judgement from the Federal Social Court," a spokesperson for Novartis' German arm said.

The Federal Social Court stipulated that a drug prescribed off label can be reimbursed in Germany only when there are no approved equivalent treatment alternatives.

The use of Avastin in AMD should consequently have ceased at the time of the launch of Lucentis, a derivative of Avastin, in February.

However, the treatment for AMD is not included in the current services immediately reimbursed by the German health insurance. Each case requires individual authorisation. The patient must pay the bill which is then reimbursed afterwards.

"Thanks to this particularity, doctors can continue to suggest Avastin instead of Lucentis," Eva Hansmann emphasised.

The federal insurance office (BVA) is assessing the legal validity of the study, a spokesperson for BVA told APM.

The German initiative is far from being unique. Ophthalmologist associations in the U.S. and the UK are reportedly preparing similar measures.

INDICATION EXTENSION IN ITALY

In Italy, Avastin received an indication extension at the end of May for AMD from the Italian medicines agency (AIFA), also at the request of ophthalmologists, Eva Hansmann explained.

In Germany, Avastin is largely used in AMD. In 2006, 25,000 out of the 35,000 treatments have employed cancer drugs. The 10,000 other treatments were mainly using the anti-inflammatory triamcinolone (6,200 cases) then Macugen (2,800 cases) and Lucentis (1,200 cases).

"Doctors are already used to Avastin in AMD while Lucentis is an unknown domain. The treatment for AMD is therefore clearly more secure with Avastin than with Lucentis," she said.

PROPOSITION RECEIVED WITH RESERVES

The health insurers are holding back with regard to the proposal from Novartis to finance treatments above sales figures of 315 million euros;.

"The game played by the industry is touching on insolence. They want to force a drug's sales and block the use of a treatment at least as effective but 22 times less expensive by refusing to develop it in this indication," commented a source close to the case.

Avastin and Lucentis are both vascular endothelial growth factor (VEGF) products by the U.S. company Genentech.

The German health insurers are looking unfavourably at the industrial manoeuvring around these products: Avastin is licensed to Roche and Lucentis to Novartis. Roche is the main shareholder for Genentech and Novartis holds 33% of Roche's capital.

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.

CATT Study Update 2: Avastin vs. Lucentis – It’s Official!

I have confirmed that the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT) is set to get underway shortly. An official involved with the CATT study has informed me that a training meeting for some of the clinical center staff – investigators, clinical center personnel and OCT technicians – will be meeting in Philadelphia on September 25-26th to co-ordinate the methods to be used in undertaking the study and evaluating its results. More than 180 people are expected to attend.

Stay tuned for further developments.

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).

The study will enroll about 1,200 patients with newly diagnosed AMD, randomly assigned to one of four treatment groups: (1) Lucentis with monthly dosing; (2) Avastin with monthly dosing; (3) Lucentis with three injections followed by additional injections of Lucentis as needed; and (4) three injections of Avastin followed by additional injections of Avastin as needed. 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 primary investigator, Dr. Daniel 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. Enrollment is now scheduled to begin in late 2007, and one year follow-up data will be reported in 2009. The study will be conducted in 40 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.