GUEST EDITORIAL

The Public's Distorted Views on CATT Data

Neither storyline taking shape in the Avastin vs. Lucentis showdown should be given credence.

By Pravin U. Dugel, MD

Truth holds a unique place in the lives of physicians. Every day we go to work in a profession with a built-in truth detector: the scientific method. Each of our professional beliefs gets double checked against this apparatus repeatedly. And despite plenty of debate, consensus even tually emerges, truth is distinguished from falsehood, and progress occurs.

It's easy to forget that most of the rest of the world does not always apprehend reality in this fashion. For many in the general public, truth arises from a series of competing narratives, each telling a story about life that may or may not correlate with facts. Unfortunately, the “truth” that emerges in the public's mind is not always the storyline that adheres closest to reality, but often the one that is most compelling, easy to understand or that flatters existing beliefs and prejudices.

Since the publication of the oneyear CATT data in May, two such narratives, divergent and seemingly contradictory, have begun taking shape in the public arena. In one, to save a few bucks, ophthalmologists are seeking to push a dangerous and untested off-label drug (Avastin) on an unsuspecting public. In the other, unscrupulous ophthalmologists are colluding with big pharma to push a needlessly expensive drug (Lucentis), lining our pockets, fleecing seniors and Medicare, while ignoring a far cheaper therapy of equal efficacy.

Though neither scenario offers much basis in reality, they have already influenced policy-makers, caught the attention of Congress, the insurance in dustry, the media, Wall Street and—depending on which version prevails—could very well culminate in restricting our patients' access to either of these drugs.

To retain optimal treatment flexibility, we first need to understand how these narratives evolved. Then we must articulate why patient well-being depends on continued access to both bevacizumab and ranibizumab, at least until far more is known about their safety and efficacy. Finally, we can make changes in our professional conduct that curtail the appearance of impropriety.

HUGE NUMBERS

The rise in anti-VEGF therapy, while enormously beneficial to so many patients, has also strained the bottom lines of health insurers, Medicare and household budgets. Last month, the department of Health and Human Services issued a report stating that in 2008 and 2009 Medicare paid $40 million for 936,382 Avastin injections and $1.1 billion for 696,927 Lucentis injections. Had physicians relied exclu sively on Avastin during those years, Medicare would have saved $1.1 billion and patients would have saved $275 million in co-payments, according to the report. Had Lucentis been prescribed exclusively, Medicare would have spent an extra $1.5 billion and patients an additional $370 million.

In other words, the numbers involved are huge. According to the Wall Street Journal, Lucentis is now the single biggest expense in the pharma budget of Medicare Part B, which covers injectables and biologics (Medicare Part D covers ordinary prescription drugs).

This summer, Senator Herb Kohl (D-Wisconsin) chaired a hearing of the Special Committee on Aging that focused on CATT results and the potential cost savings of Avastin. Philip J. Rosenfeld, MD, PhD, who pioneered the off-label use of bevacizumab, gave excellent testimony on how CMS and Genentech provide cost incentives that discourage the use of Avastin.

For example, CMS provides an additional payment of 6% of the average sales price of the drug, which for Lucentis amounts to $115 per injection; CMS decreased reimbursement of Avastin for hospital-based practices from $50 to $7, and threatened to do the same for private practices, which caused many to switch to Lucentis as a precautionary measure; and he cited a 2010 New York Times exposé detailing bulk rebates on Lucentis offered by Genentech that could net practices as much as $58,000 per quarter. Aside from the ethical dilemma they pose, Dr. Rosenfeld wondered why such rebates should go to physicians.

“After all, isn't CMS paying for the drug?” Dr. Rosenfeld asked.

In addition, some prominent hospitals have been designated “disproportionate share hospitals” (DSH) by Medicare, meaning that these hospitals serve a “disproportionate” percentage of indigent patients. As an incentive, DSH hospitals are allowed to buy drugs at a 20% discount and get reimbursed at market price. With this designation alone, such hospitals make a $400 profit on each vial of Lucentis. Staff physicians who use Lucentis regularly in such hospitals are huge profit centers. Such physicians may benefit directly or indirectly for using, and propagating the use of, Lucentis.

Though Dr. Rosenfeld stressed that no clinician, himself included, wanted CMS dictating which drugs to use, he believed addressing these financial incentives could save the government billions.

Meanwhile, CATT data has also influenced insurance companies. In my capacity as research and therapeutic chair for ASRS, I have helped to draft several letters refuting private insurance carriers seeking to mandate Avastin as a first-line drug—the so called “step therapy” requirement. A few small insurance companies have already instituted this requirement in some markets.

Circumstances seem ripe for heavy-handed government restrictions. Though the HHS report did not call outright for Medicare to drop its coverage of Lucentis, it did ask CMS to “consider the results of this report when evaluating coverage and reimbursement policies” and to “evaluate its current authorities and seek additional authorities as necessary to control Part B drug and biological expenditures more effectively” [emphasis mine].

COMPOUNDING PROBLEMS

Conversely, two recent outbreaks of endophthalmitis in Florida and Tennessee traced to contaminated batches of Avastin may tarnish the off-label therapy's reputation. Under the alarmist headline “Avastin Injections Are Reported to Cause Blindness” a recent New York Times story described 16 patients who suffered infections, some of whom were blinded. Although the article does eventually mention the compounding pharmacy, it gives the impression that the inexpensive nature of the drug somehow contributed to the infections.

Though these are the first serious problems reported with Avastin after six years and more than two million injections, a story like this might still have enormous consequences. It is telling that most of the newspaper's sources were lawyers. You can bet plaintiffs' attorneys nationwide are out beating the bushes for Avastin patients, hoping to link any health problems they may have to the drug. Indeed, the stock-picking Web site Seeking Alpha estimated that a competing therapy currently seeking FDA approval could have “a larger-than expected end market” because of the damage the infection outbreaks are likely to have on Avastin's standing.

MUDDY WATERS

It's easy to see how these two storylines could capture the public imagination. They contain just enough truth to be believable, while gleefully defenestrating humdrum subtlety and nuance.

Both depend on the misconception that CATT effectively made these drugs interchangeable. In fact, CATT only provided one-year data, and outcomes could easily diverge at year two or beyond. Additionally, safety problems may yet emerge with Avastin.

Moreover, patients sometimes respond to one drug but fail to respond to the other. Or an initial response to one drug wears off over time, only to be revived by substituting the other. No one is certain why such variable responses occur, but clinicians should be free to develop anecdotal theories and prescribe accordingly. Restricting one therapy at this point would squelch such freedom. We should also retain the ability to substitute Lucentis for patients with cardiovascular problems.

To avoid the appearance of impropriety, we as a profession should decline to participate in rebates offered by Genentech, or at least notify patients if we do. Rebates are not illegal, nor do I believe practitioners intentionally skew their therapy choices to obtain them. But when the price of the rebated drug dwarfs the alternative to the degree that it does in this case, we cannot hope to avoid public outcry if we take part. Similar ly, physicians who practice in a DSH-designated hospital should disclose their unique economic incentive to both their patients and colleagues.

On the Avastin front, we should take greater care in choosing compounding pharmacies, since we will be held responsible for their work. In 2004, the United States Pharmacopeia provided voluntary safety guidelines for compounding pharmacies, and compliance with them should be a determining factor in partnering with a pharmacy.

Despite the hit Avastin's reputation has recently taken due to the infection outbreak, bevacizumab remains my first-line drug. To my mind, all things being equal, why not save the patient and society money? This is a decision I'm happy to arrive at of my own volition. But I would never condone any CMS effort to deprive my colleagues of the opportunity to arrive at a different conclusion—provided they are forthright with patients and colleagues about any financial implications.

No matter what, we must do everything possible to retain our ability to chart a different course if it becomes necessary. RP