Who will pay for the trial’s drugs?

NEI Awaits CMS Policy Decision on AMD Clinical Trial

The much-anticipated study comparing the two top drugs used in the treatment of neovascular age-related macular degeneration (AMD) has stalled. The National Eye Institute (NEI), which would fund the study, is awaiting a decision by the Centers for Medicare & Medicaid Services (CMS) on whom should pay for the drugs [ran-izumab (Lucentis, Genentech) and bevacizumab (Avastin, Genentech)].

AMD study background

In October 2006, the NEI an-nounced it would fund a multicenter, four–armed, randomized clinical trial to compare ranizumab — a drug approved for the treatment of neovascular AMD — with bevacizu-mab — a colorectal cancer drug that has been used off-label to treat neovascular AMD since 2005. The trial will include 1,200 neovascular AMD patients.

The trial will examine fixed monthly doses of both drugs, as well as compare ranizumab given on a fixed schedule once every four weeks vs. bevacizumab given as needed and vice versa, says Daniel F. Martin, M.D., professor of ophthalmology at Emory University School of Med-icine and the study’s chair.

The trial’s outcome

The outcome of the trial will address:

► Safety and efficacy. “Eye-care practitioners have treated tens of thousands, if not hundreds of thousands of eyes, with intravitreal bevacizumab, indicating it has been used much more than ranizumab clinically,” says Dr. Martin. “Yet, researchers have not fully evaluated the safety and efficacy of bevacizu-mab in a prospective, randomized clinical trial. The anecdotal experience suggests that it [bevacizumab] is safe and effective, but this trial will enable us to assure our patients of this.”

► Dosing. “Most practitioners are using ranizumab based on our anecdotal experience with bevacizumab. Patients receive one, two or three injections initially and are followed for progression of disease by optical coherence tomography (OCT), visual acuity tests and sometimes fluorescein angiography,” Dr. Martin says. “Retreatment is subsequently offered on an as-needed basis. This study would provide us with assurance that this dosing strategy is effective but does not compromise long-term visual outcome.”

► Cost. An injection of ranizumab costs $50 or less per injection for 80% of wet-AMD patients because Medicare and other insurers cover the injection, says a spokesperson for Genentech. The spokesperson says the company does not know what the average co-pay for bevacizumab is for the treatment of wet AMD because there isn’t a standard dose, each pharmacy charges a different amount to make up the solution, and the coverage for this off-label use varies by state.

While the actual cost of ranizu-mab to the patient may be similar to that of bevacizumab, “ranizumab costs Medicare $2,000 per injection vs. bevacizumab, which costs Medicare about $50 per injection,” says optometrist Jeffrey Gerson, of Shawnee, Kan., who has followed “hundreds” of wet AMD patients. “Therefore, if bevacizumab is proven to be as safe and effective as ranizumab, that could mean savings for both tax payers and patients.”

A spokesperson for Genentech says, “This trial is being looked at by physicians and by patients to answer certain questions with regard to safety and efficacy, and the NEI head-to-head proposed trial should be designed to answer those questions because physicians and patients are going to be making treatment decisions based on it. We have concerns about the way the trial is designed and whether or not it has the ability to answer those questions.”

The company has two concerns, according to the spokesperson: Bevacizumab does not meet ophthalmic standards put into place by U.S. Pharmacopoeia guidelines (the drug is designed to meet intravenous standards for patients who have cancer.) Also, no one has conducted formal dose ranging studies for bevacizu-mab, so Genentech doesn’t know what dose of the drug would be effective for treating patients in the NEI study.

As for the cost to tax payers, the Genentech spokesperson says: “I think it’s important to remember that until ranizumab was approved, treatments could only slow the progression of wet AMD, meaning that people still continued to have problems associated with vision loss, such as having to move into assisted living facilities and falling and fracturing their hips. So, we would anticipate that some of the cost of ranizumab would be off-set by not having those ancillary complications of vision loss.”

Further, the company says it offers a number of programs to ensure patients have access to its therapies. (See http://www.gene.com/gene/about/views/pricing/patient-access.jsp.)

The CMS’ role

According to an article appearing in the Feb. 22 issue of The Wall Street Journal, Genentech said the NIH should be “studying cutting-edge science, not comparing two approved drugs.” The company has declined to supply the two drugs in question for the NEI trial as well as any funding. This prompted the NEI to seek help from CMS.

Under CMS’ Clinical Trial Policy National Coverage Determination (NCD), a policy established to pay for routine patient costs in clinical trials, the CMS cannot pay for either ranizumab or bevacizumab, according to a spokesperson for CMS. However, the Medicare Evidence Development and Coverage Advisory Committee recommended that CMS change that provision of the policy (as well as other provisions), and the Clinical Trial Policy has been open for reconsideration, with a proposed decision due April 10th. (For more information, see http://www.cms.hhs.gov/mcd/viewtrackingsheet.asp?id=186.)

When asked from whom Dr. Martin and his colleagues will seek funding should the CMS policy not be able to cover the study, Dr. Martin says he cannot comment at this time.