Article Date: 10/1/2011

SUBSPECIALTY NEWS
SUBSPECIALTY NEWS

HHS Study Finds Avastin Cost Advantage

But infections heighten safety concerns, prompt VA ban.

Jerry Helzner, Senior Editor

■ Medicare could have saved more than $1 billion in just two years if Avastin had been mandated as the only anti-VEGF drug for the treatment of wet AMD, the HHS inspector general (IG) reported recently following an audit. Medicare beneficiaries would also have saved $275 million, the IG said. The IG noted that Lucentis now accounts for the single largest cost item in the Medicare Part B injectable and biologics formulary.

On Sept. 6, HHS issued a report on the costs that Medicare incurred for coverage of Lucentis and Avastin to treat wet AMD in 2008 and 2009. Medicare paid $40 million to physicians for 936,382 Avastin injections and $1.1 billion for 696,927 Lucentis injections. They then calculated the potential savings if ophthalmologists had used Avastin exclusively:

Medicare would have saved $1.1 billion and patients would have saved $275 million in copays. In the opposite scenario—with Medicare reimbursing only Lucentis—Medicare would have spent $1.5 billion more and patients $370 million more.

With Lucentis costing Medicare about $2,000 per injection as compared to about $50 for each injection of off-label Avastin, the IG would like Medicare to ask Congress for more power over pricing, particularly with costly biologics like Lucentis. CMS currently has no power to mandate price concessions or rebates from drug companies.

However, cost concerns are not the only issue in play when comparing Lucentis to Avastin. Two recent incidents in which tainted Avastin caused a total of 16 endophthalmitis infections in south Florida and in a VA facility in Nashville have raised new safety issues related to the role of compounding pharmacies in breaking down Avastin into single-dose syringes for use in the eye. The Department of Veterans Affairs dropped its use of Avastin in response to the outbreak.

Lucentis has also been touted as the safer drug by some who argue that a Johns Hopkins study of mortality figures and also the CATT study data reveal a lower incidence of serious adverse events for Lucentis. “Any action CMS takes to encourage the use of Avastin to treat wet AMD could be controversial,” the IG commented in its report.

Philip Rosenfeld, MD, PhD, of Bascom Palmer Eye Institute, who pioneered the use of Avastin in the treatment of wet AMD in 2005, defended the continued use of Avastin despite the two recent incidents.

“It took six years for something like this to happen,” he told the New York Times, noting that there have been more than two million injections of Avastin into eyes in the United States alone since the practice began in 2005. He said careless procedures at compounding pharmacies were the most likely cause of the two incidents.

A month prior to the reports of the infections from tainted Avastin, Dr. Rosenfeld had testified before the Senate Special Committee on Aging as to the history of Avastin as a treatment for wet AMD and the large cost savings generated by using this alternative treatment.

He also criticized the existence of incentive programs, including rebates paid by Genentech for volume use of Lucentis and cash-back programs for credit card purchases of Lucentis.

“The current system has many attractive incentives that encourage the use of Lucentis,” Dr. Rosenfeld told the committee. “When added up, a busy clinical practice can make 6% on the average selling price, another 1% to 2% by using a credit card, and an unknown amount if the rebate program exists. For a private practice, these incentives amount to a healthy return on a $2,000 investment every month. In a Disproportionate Share Hospital designated hospital-based practice, the incentives are even greater” because of the up to 20% discounton medication purchases given to hospitals that provide a disproportionate amount of indigent care attheir facility.

“As a clinician, I don't want CMS telling me which drug to use, and I don't want patients worrying that the decision to inject their eye is being influenced by financial incentives,” asserted Dr. Rosenfeld in his testimony. “By addressing the financial incentives that currently promote the use of the most costly alternative, CMS could level the playing field and allow physicians and patients to focus on efficacy, safety and cost when deciding between drugs.”

Release of the two-year CATT data in 2012 will likely prompt further reevaluation of the anti-VEGF landscape as more is learned about the drugs' relative efficacy in patients switched to PRN regimens for the second year, as well as providing additional safety data for both Lucentis and Avastin.

IMT Shown to Improve Quality of Life

Study: End-stage AMD patients benefit greatly.

■ Significant vision improvement enabled by an implantable miniature telescope (IMT) can make a major positive difference in the quality of life of some patients with end-stage AMD. Findings of a two-year study were recently reported in Ophthalmology.

In related IMT news, CMS has granted transitional pass-through payment status and established a billing code for the IMT under the Hospital Outpatient Prospective Payment System. The new passthrough code, C1840, became effective on Oct. 1, 2011 and will enable outpatient facilities to obtain reimbursement for the telescope implant for covered procedures. The telescope implant was approved by the FDA in 2010 as a way to improve vision in patients with end-stage AMD.

Eligible patients must have associated central vision blindness and either stopped responding to AMD medications, or have a form of the disease for which no treatment is currently available.

By the end of the two-year study of 76 patients, whose average age was 75, vision improved from a mean of 20/326 to 20/141 in patients who received the 3x model IMT. Most patients could once again see people's faces rather than just blurry outlines, and could get around the market or their backyard on their own. Overall, the study found that these IMT patients' lives improved substantially and at a reasonable cost. Quality of life was measured using a system called human value gain, with standards based on the actual experiences of people with vision loss. The study was led by Gary C. Brown, MD, MBA, of the Center for Value-Based Medicine.

“Only by ‘walking a mile in a patient's shoes' can we understand the true impact of vision loss and the value of restored sight,” Dr. Brown said.

The FDA approved the IMT in 2010. Only patients who meet strict criteria, pass pre-surgery tests with an external eye telescope and agree to vision training afterward are eligible. The FDA plans to follow IMT patients for at least five years to check for long-term effectiveness and safety.

IMT surgery and related care cost $18,494 per patient. But restoring vision often eliminates the need for other medical services. Dr. Brown's team subtracted costs that these patients would probably not incur, such as treatment for depression and vision-related injuries, skilled nursing care, nursing home facilities and other costs; this brought IMT treatment down to $14,389. Medicare covers IMT treatment in some states.

The report also compared IMT treatment to several widely accepted medical treatments in terms of how much each improved both length and quality of life. The IMT scored better than treatments for high blood pressure, enlarged prostate, osteoporosis and other common illnesses.

Trade-offs required by the IMT include sacrifice of some peripheral vision that must be compensated for in the fellow eye, disruption of the central visual field and the inability to adjust the magnification level after implantation, low vision specialist Donald Fletcher, MD, pointed out in Retinal Physician's October 2010 issue.

“By trapping the low vision enhancement device in the patient's eye, a solution that works well initially may present a problem when it is no longer optimal with progression of the disease,” Dr. Fletcher noted.

IN BRIEF
Questions you can ask a compounding pharmacy. In the wake of two recent incidents of tainted Avastin that caused serious eye infections, the Ophthalmic Mutual Insurance Company has posted on its Web site at www.omic.com a number of questions that you can ask a compounding pharmacy to ensure that it is properly credentialed and following the recommended safety guidelines for the compounding of drugs. Go to the “blog” icon on the right and scroll down to the post of August 11 for the relevant questions that can help you determine whether a compounding pharmacy is operating at maximum safety levels.
Sterility testing for Avastin. Vanderbilt Eye Institute, which has its own compounding pharmacy, has added an additional safety step in the wake of incidents involving infections caused by tainted Avastin. Though not having any previous problems with the drug, Vanderbilt told the Nashville Tennessean that it has introduced a sterility test that is conducted prior to the drug being sent to the clinic for use in treatment.
Waiting for HARBOR trial data. Much-awaited data from Genentech's HARBOR trial using a 2 mg dose of Lucentis in wet AMD is due to be released at this month's AAO meeting. One major question to be answered is whether a regimen employing a 2 mg dose of Lucentis could equal or approach the efficacy of a 2 mg dose of Eylea (formerly VEGF Trap).
When Regeneron released its phase 3 results for Eylea as a treatment for wet AMD earlier this year, the basic comparison was between a 2 mg dose of Eylea and a 0.5 mg dose of Lucentis, a comparison which benefited the Regeneron drug.
Retina specialists are eager to see if the HARBOR trial results will somewhat level the playing field.
Opko sells imaging business. Opko Health is selling its ophthalmic instrumentation business to Optos, Inc., a subsidiary of Optos plc, a medical technology company engaged in the design, development, manufacture and marketing of devices to image the retina of the eye. Optos will pay Opko $17.5 million in cash at closing, plus future royalties.
Optos is acquiring Opko's worldwide activities for the development and commercialization of ophthalmic diagnostic imaging systems and says it will combine Opko's OCT SLO technology with Optos' widefield technology to provide an advanced tool to diagnose and manage diseases of the eye.
Drug for LCA/RP is fast-tracked. QLT Inc. said the company's oral synthetic retinoid for retinal diseases, QLT091001, has been granted two Fast Track designations by the FDA for the treatment of Leber's Congenital Amaurosis due to inherited mutations in LRAT and RPE65 genes and for the treatment of autosomal recessive retinitis pigmentosa due to inherited mutations in LRAT and RPE65 genes.
Sirolimus in phase 3 uveitis study. Santen Inc. is initiating a global phase 3 clinical study evaluating its investigational drug sirolimus (formerly rapamycin) for the treatment of noninfectious posterior uveitis.
The SAKURA study is a multinational, multicenter, randomized, double-masked study assessing the safety and efficacy of three different doses of sirolimus
The doses will be administered every two months in subjects with active, non-infectious uveitis of the posterior segment. Approximately 500 subjects with posterior, intermediate or panuveitis will be enrolled at approximately 150 sites.

Letter to the Editor

I read the article “Trying to ‘End Run' New OCT Coding? A Bad Idea You Should Not Pursue” (Retinal Physician, April 2011) and am concerned.
The issue of OCT and fundus photos being mutually exclusive by Medicare stems not from science but from the time when glaucoma doctors took photos of the optic nerve and performed an OCT at the same visit. Medicare determined that one did not give more information than the other. However, in the case of evaluating the macula, the OCT and fundus photographs (which in my office includes color, red-free and autofluorescence images) give different, complementary information.
The fundus photo is taken for two reasons: one is to document accurately what exists today, and the second is to use the photo as a comparison to determine change at the next visit. Both are important in clinical decision making to determine whether an injection is needed today or if the treatment interval can be extended. Memory or fundus drawings are not as accurate as a photograph. A speck of new blood, lipid or subtle pigment change strongly suggests progressive disease, which will change the management of the patient.
In these cases the OCT may not show a change or even the presence of fluid, and of course does not readily depict a fleck of lipid, a small dot hemorrhage or pigment changes. It is well documented that a fluorescein angiogram, which shows leaking and growing vessels, may co-exist with an OCT, which shows no fluid. Both are important tests to adequately evaluate the macula.
It is a shame that the AAO and retina specialty societies have tolerated this lumping of photos with OCT tests and have not vigorously challenged this bundling decision. Whether paid for or not, it is good medical care to obtain both fundus photos and an OCT. If the government determines one or the other is unnecessary and refuses to pay for it is not my issue, it is in my patient's best interest to do both. If the government determines to pay more for one test than the other is not my issue either, it is in my patient's best interest to do both. We must never forget we are the patient's advocate and keep their best interests in mind.
Paul E. Tornambe, MD, Poway, Ca.


Retinal Physician, Issue: October 2011