Friday, February 23, 2007

Avastin/Lucentis Update 12: The Controversy Makes the Front Page of the WSJ

On February 22nd, Marilyn Chase of the Wall Street Journal’s staff, in a front page article, reported on the controversy both within Genentech and outside, between retinal specialists, on the use of either the high-priced, FDA approved for AMD Lucentis, and the much lower-priced but off-label use of the FDA approved (for colorectal cancer) Avastin for treating "wet" age-related macular degeneration. I would like to claim at least a little credit for the story, as I urged Ms. Chase (and a number of other investigative reporters) to take a look behind the rumors that some medical and pharmaceutical companies were trying to stop the upcoming NEI/NIH trial to compare the effectiveness of Avastin versus Lucentis, after posting my Update No. 9: A Disturbing Report... on December 2nd.

Following Ms. Chase’s story on Genentech that appeared in the Journal on January 11th, I wrote her with a link to my posting above. Then following the posting of the White Paper, Why Avastin vs Lucentis Matters, prepared by a group of retinal specialists alarmed by the public health implications of the high cost of Lucentis to society (Update No. 11 – published February 10th), I again urged Ms. Chase to pursue the cause. The result was yesterday’s story.

Because of Copyright laws, I will only publish excerpts of Ms. Chase’s story. Anyone wishing to see the complete article can go to http://www.wsj.com/ (if you are a subscriber to the online edition of the Journal), or send me an email and I will be happy to respond with a copy of the story.

BLIND AMBITION

Genentech's Big Drug For Eyes Faces a Rival

Intended for Other Use, Cheaper Injection Is One of Its Own Products

By MARILYN CHASE (February 22, 2007; [WSJ] Page A1)

SAN FRANCISCO -- For some of her patients at risk of blindness, retinal specialist Anne Fung injects the drug Lucentis, which costs nearly $2,000 a shot. For those who have less health coverage, she offers a shot of another drug, Avastin, that costs around $40.

The two drugs are both made by Genentech Inc. They work similarly. Doctors say both can be effective in preventing or even reversing vision loss. But only Lucentis is approved by the Food and Drug Administration to treat eye problems.

...The Lucentis-Avastin showdown has thrown the pharmaceutical world into a tizzy. Genentech, fearful that a potential billion-dollar-a-year product could be headed down the tubes, is urging doctors to stick to Lucentis and its proven efficacy in treating age-related macular degeneration. Doctors are weighing benefit and cost -- and often choosing to roll the dice with Avastin, although it is approved only as a cancer treatment, to ensure that less well-off patients get treatment.

Now the federal government is hoping to settle the dispute by funding a head-to-head comparison of the two biotechnology drugs, the first such trial by the National Institutes of Health. If Avastin works as well as Lucentis, the government's Medicare program for the elderly could save $1 billion or more a year, officials say.

The mutiny by doctors nationwide against a high-priced drug -- and Washington's willingness to go to bat for them -- is triggering alarms in the drug industry. "Industry doesn't want an equivalency trial where there could be decisions on coverage. They are terrified," says William L. Rich, director of health policy at the American Academy of Ophthalmology, which backs the NIH trial.

...For Genentech, the world's second-largest biotechnology company by revenue after Amgen Inc., the stakes are high. Lucentis was a surprise hit after its June 30 launch, logging $10 million in sales on its first day and $371 million in the second half of 2006. Eric Schmidt, an analyst at Cowen & Co., estimates the figure could reach $900 million this year and rise to $1.3 billion by 2011.

Genentech has refused to provide any funding or drugs for the NIH trial, scheduled to start in April. The Biotech Industry Organization says the NIH should be studying cutting-edge science, not comparing two approved drugs. Genentech's head of business development, Joseph McCracken, adds: "If I were trying to decide how to spend NIH's money, I might not think this is the best way."

...Doctors are using Lucentis and Avastin to treat "wet AMD," a type of the disease in which overgrowth of blood vessels and leakage of fluid cause gross swelling of the macula, a part of the retina.

...Avastin fights cancer by halting the growth of blood vessels that sustain tumors. The FDA approved it as a cancer treatment (for colorectal cancer) in 2004.

More than a decade ago, research suggested that taming vessel overgrowth might also be used to treat diseases of the eye. But based on early tests in monkeys using a similarly sized molecule, Genentech thought the Avastin molecule was too big to penetrate the retina. Its scientists spent two years re-engineering it to create Lucentis, which then underwent seven years of testing.

...In July 2005, Genentech reported the results of a big Phase III study of Lucentis before a hushed crowd of 2,000 at a medical meeting in Montreal. The studies showed it halted blindness in 90% of people with AMD and improved vision in 30%.

"There was an audible gasp," recalls George Williams, chairman of ophthalmology at the Beaumont Eye Institute in Royal Oak, Mich. Lucentis "was so much better than anything else." Previously the disease was treated with less-effective drugs, photodynamic therapy and lasers -- "like using a blowtorch to stop weeds," says Dr. Fung in San Francisco.

The only problem: Approval would take another year.

Then came an apparent solution: At the same meeting, Philip Rosenfeld, a professor at the Bascom Palmer Eye Institute of the University of Miami Medical School, presented a case of a patient who had been going blind and was injected with Avastin. The patient's retinal scans dramatically improved a week after treatment and vision began to regain sharpness over six months.

It was a review of this meeting, the July 2005 American Society of Retina Specialists held in Montreal, by Lynne Peterson in her Trends-in-Medicine newsletter, that piqued my interest, and started my journey in reporting on the Avastin (and later Lucentis) phenomenon, beginning with my posting of January 31, 2006, Avastin: A New Hope for Treating AMD.

Over the following year plus, that initial posting was followed by an additional 12 reports on the status of the two drugs in treating wet AMD. See the Author’s Notes at the end of this posting for a complete listing and links to each story.

...Rather than wait until Lucentis was approved by the FDA, many doctors grasped at the next best thing. With the help of compounding pharmacists who siphoned tiny doses of Avastin into small syringes, eye doctors tried it in thousands of patients. In large doses for cancer, Avastin costs $55,000 a year. The dose used in the eye costs just $20 to $100.

"People thought we were cowboys, but we were doing it in our patients' interests," says Robert Avery, an ophthalmologist in Santa Barbara, Calif. "When people are going blind, they're willing to take risks."

Even after Lucentis received FDA approval last year (June 30, 2006), many doctors stuck to Avastin because a comparable Lucentis injection costs $1,950. "This is a public-health issue," says Dr. Rosenfeld of Miami. "I believe in profit but things are out of proportion."

See also the above mentioned White Paper: Why Avastin vs Lucentis Matters, for more discussion on the public health issues on the costs to society of the continued use of the high-priced Lucentis.

...Last month, the American Society of Retina Specialists found in a survey that doctors preferred Avastin over Lucentis 76% to 9% for their Medicare patients. Even when patients had supplemental insurance policies that covered the patient's cost, the margin was 51% to 43%.

Genentech argues Lucentis is the only product shown to safely restore vision and Avastin remains unproven as an eye treatment. "I've seen anecdotal reports. They're impressive. But they're still single-case reports," says Susan Desmond-Hellmann, the company's president of product development. She cites the mom test: "If my mom had [AMD], I'd want her to get the drug that is safe and effective."

...Genentech, in justifying the cost of Lucentis, says its trials of the drug included more than 6,000 patients who received vision tests, retinal scans and monthly doctor checkups. It was "one of the more expensive clinical trials we've run," says Ronald Park, team leader for pricing. He notes that older drugs for AMD cost nearly $1,000 a dose without improving vision. Lucentis "is a breakthrough drug for a very bad disease," says Dr. Park.

The company also reasons that Lucentis could prevent disability, falls, broken hips and depression associated with blindness. The elderly blind "become more dependent on those they love to drive, get food, help around the house. Until you've seen someone who was independent go blind -- and I've treated these folks -- you don't understand how terrible this can be," Dr. Park says. The American Academy of Ophthalmology this month said blindness costs the health-care system more than $2 billion a year including nursing-home care.

Finally, Genentech says it is happy to help those who can't afford Lucentis. Since Lucentis's approval last summer, 15,000 patients have called the company's assistance programs asking about the drug, a spokeswoman says.

...With billions of dollars at stake and medical questions unanswered, the National Eye Institute plans to start a two-year trial in May or June to compare safety and efficacy of Avastin versus Lucentis. While the NIH has previously run tests comparing newer brand-name drugs against older and cheaper generics, this is the first time it is pitting two brand-name biotech drugs against each other, says Dr. Ferris, the eye institute's clinical director. He says the government must conduct the study because it needs to ensure that the widespread use of Avastin is safe.

Daniel Martin, chair of ophthalmology at Emory University School of Medicine, is leading the NIH trial and has selected 45 test sites for it. He offers his own mom test. "If I were treating your mom, you'd want me to know which drug is better," he says. "And if they're equal, why not use the less-expensive one?"

However, funding for the trial remains uncertain. In part because the government has to purchase all of its Lucentis and Avastin supplies, the eye institute says it can't afford to fund the trial on its own and is seeking help from Medicare.

Barry Straube, chief medical officer of the Center for Medicare and Medicaid Services, says he welcomes the trial as a guide for reimbursement policy, but lawyers for the agency have said it lacks legal authority to use the Medicare trust fund for such research expenses. Dr. Martin says the NIH has awarded $16.2 million for the trial and he'll seek additional funds elsewhere if needed.

Officials at the center, which administers Medicare, project that Lucentis could over time cost taxpayers more than $1 billion a year and possibly as much as $3 billion annually. Dr. Straube says he would be pleased if that figure can be reduced. "Not only are we interested in preserving the Medicare trust fund, but we're sensitive to the higher co-insurance payment Medicare beneficiaries would have to pay," he says.

Genentech says some of the projections of the Medicare impact are too high, noting analysts' estimates that this year's total sales will fall short of $1 billion.

For the moment, the company's data suggest Lucentis has captured about 55% of the market in new cases of AMD. Doctors' surveys suggest Avastin has captured much of the rest. That "unique situation," Executive Vice President Ian Clark recently told analysts, "will challenge our rate of growth of Lucentis in 2007."

Author’s Note on Avastin

Since posting the original article on January 31, 2006, I have now added twelve updates on this important drug for treating age-related macular degeneration. In addition to the posting you are reading, here is a listing (with links) to the others:

posted by Irv Arons @ 12:49 PM   8 comments

Wednesday, February 14, 2007

NeoVista Epi-retinal Strontium 90 Treatment for Wet AMD

In my attempt to keep readers of this web site apprised of potential new treatments for age-related macular degeneration, I would like to present early positive results for a brand new treatment for AMD. The new vice president of sales & marketing at NeoVista, Tony Moses, an old friend, sent me a copy of the presentation of the recently presented first results for using strontium 90 in combination with a VEGF drug to alleviate vision loss in wet AMD. With his permission, here are the facts to date.

On January 16, 2007, Dr. Andrew Schachat, Vice Chair for Clinical Affairs, Vitreoretinal Department of the Cole Eye Institute, presented the first data on NeoVista’s Epi-Rad 90 Ophthalmic System at the Hawaiian Eye meeting (RHEM). The procedure involves the epi-retinal application of strontium 90 radiation for the treatment of wet AMD. A review of some of the early findings from his presentation are reported below.

Radiation treatment for AMD

NeoVista, Inc., of Fremont, Calif, released data demonstrating a potential benefit of treating wet AMD with radiation using the company's Epi-Rad 90 Ophthalmic System. Clinical data was presented from 2 separate feasibility studies that utilized the NeoVista product. The first study, involving a total of 24 patients, comprised 2 different doses of radiation (15 Gy and 24 Gy) delivered to the retina. The second study, which involved 20 patients, utilized a concomitant approach of 24 Gy radiation plus Avastin, where an injection of the drug was administered at the time of radiation treatment and an additional injection administered 30 days later. This is the approach the company plans to follow when it begins its pivotal 450-patient CABERNET trial this year. The company will utilize Lucentis instead of Avastin in this trial.

The Procedure and Early Results

The procedure involves performing a partial vitrectomy under local anesthesia. The delivery of the radiation takes between 3 and 5 minutes, depending on the calibration certification for the device being used, while the total procedure takes about approximately 40 minutes. The focal radiation penetration is about 3 mm into the choroid. The company claims that the ionizing radiation has a toxic effect on local pro-inflammatory and fibroblast cell populations, permanently disabling the proliferating CNV Cells.

In the two feasibility studies, using radiation alone, the lower dosage test (15 Gy) was not impressive, showing a loss in visual acuity after 9 (-2.4 letters) and 12 months (-3.2 letters).The study utilizing a higher dosage of strontium 90 (24 Gy) had better results, showing an increase in visual acuity after 9 (+5.6 letters) and 12 months (+7.6 letters). This compared favorably with the MARINA study of Lucentis, which had an increase of +7.2 letters after 12 months.


However, the second study, which utilized a concomitant approach of 24 Gy radiation plus Avastin, where an injection of the drug was administered at the time of radiation treatment and an additional injection administered 30 days later, was even more impressive. After only 2 and 3 months followup, the 20 patients showed an increase in VA of +14.2 and +14.9 letters, beating the MARINA study results by a wide margin.


Eugene de Juan, Jr., MD, the Jean Kelly Stock Professor of Ophthalmology at the University of California San Francisco and the inventor of the NeoVista treatment approach, commented, "Although the follow-up period (3 months) is relatively short, the results observed from the concomitant trial are extremely encouraging. The percentage of patients who improved in visual acuity by greater than 3 lines was reported at 50%, which is far above the 34% that was reported in the Lucentis MARINA Study. Granted, the NeoVista sample size is much smaller than that garnered from MARINA, but the evidence does support a closer investigation of this concomitant approach."

"We continue to see vision stability, and in many cases, vision improvement after just one treatment," stated John Hendrick, President and CEO of NeoVista. "The potential impact of our technology will greatly benefit patients, physicians, and the overall health care system. We will soon begin our Pivotal Trial incorporating concomitant use of Lucentis and Epi-Rad 90 therapy. The encouraging results observed in our concomitant feasibility trial have us excited about the future of this approach."

CABERNET Trial Design

According to the company, the CABERNET trial will involve 450 patients, with 300 receiving the 24 Gy dosage of strontium 90 plus Lucentis, and the control arm of 150 patients will receive Lucentis only. The study, to begin later this year, is scheduled to be held at 30 sites worldwide, 20 in the U.S. and 10 OUS. We will keep you informed on more details of the new trial as we learn them.

Questions & Answers

After reviewing Dr. Schachat’s Powerpoint presentation, I asked several questions of the company’s Vice President of Marketing & Sales, Tony Moses. Here are my questions and his responses:

1. Isn't even a partial vitrectomy more invasive than just the injection used for Lucentis/Avastin?

Any vitrectomy is naturally more invasive than an injection. What is not known, and what concerns many physicians is the potential outcome of numerous intraocular injections over time.

2. The higher dose appears to work better than the lower dose (duh!), but with a higher percentage of adverse results. Are there other dangers from the higher radiation dosage to the retina?

The only noticeable adverse effects in either group is the number of cataracts caused by our procedure, which is still in line with that reported by Lucentis in their MARINA data. To date (and we now go out to 18 months with some patients) there are no other significant adverse effects to report. Physicians are still concerned with the potential of causing radiation retinopathy, although we have seen no such cases yet.

3. How often does the treatment have to be repeated? (I don't think I saw that in looking quickly at the presentation.)

In our current data set, no patients have required a second procedure and we have strong belief in duration effect out past two years. We have this belief from reviewing the data from the initial sub-retinal approach to this procedure, first attempted by Dr. Eugene de Juan in 2003.

4. Your results with using both strontium 90 + Avastin appear to be additive. Perhaps that is the way to go?

You are absolutely correct! This is our approach going forward in our CABERNET Trial. Surgery plus one Lucentis injection at the time of surgery and then one booster injection at day 30 post-op.

5. Do you have an estimate of the cost? How will it compare, say, to a year's treatment with Avastin?

We estimate that our procedure will cost roughly $6,000 over a two year period, exclusive of the drug cost. To compare it to Avastin will be difficult since we have no data on the number of annual injections required to temper the disease. If we use Phil Rosenfeld's data from PrONTO, the number is roughly 6 per year. At $50 per injection (typically paid by the patient) plus the cost of injecting the drug ($200 for 2007) the Avastin cost will total ~$1,500 per year, not counting the cost of all exams. Please keep in mind that even though the patient may not require monthly injections, they must still be seen every 4 to 6 weeks to confirm disease stability. And, since the drug is not curing the disease, patients will likely have to continue this approach on an ongoing basis. This is one of our potential benefits - less burden on both the patient and the physician.

posted by Irv Arons @ 4:06 PM   1 comments

Saturday, February 10, 2007

Avastin/Lucentis Update 11: A White Paper on Why Avastin vs Lucentis Matters

This White Paper was written by a group of retinal specialists (listed at the end), who are alarmed by the public health implications of the high cost of Lucentis. They have been trying to gather grassroots interest within their profession, with hopes of eventually getting the ear of legislators. Attached is their essay that summarizes the medical issues involved, their concerns, and their recommendations.

This paper is reproduced with permission of the authors.

Avastin versus Lucentis: Why It Matters

Although Lucentis is a remarkably safe and effective treatment for exudative macular degeneration, it could cost our health care system billions of dollars annually, which will be a significant burden on our strained health care system. Fortunately, it appears that Avastin is roughly equal to Lucentis in safety and efficacy, and Avastin’s far lower cost makes it an attractive alternative. We encourage wider use of Avastin, which can help sustain the health care system that has benefited our patients medically and ourselves professionally.

Growing health care expenses (to which rapidly rising drug costs have contributed heavily) are unsustainable. In response to these growing costs, Medicare has been attempting to reduce all physician fees, a move Congress blocked at the last minute in 2006. Right now, ophthalmology faces annual cuts of 1% for four years, a 3% cut in 2007 for certain commonly used ophthalmology codes, and the prospect of further Medicare cuts in the future. Just as legislators targeted cataract fees as a way to reduce health care expenditures, it cannot serve ophthalmology well if huge pharmaceutical expenses result in an explosive growth in federal expenses for ophthalmic care. Fortunately, there are things all ophthalmologists can do to address these challenges.

How Might Lucentis Affect Physician Compensation?

Medicare Part B pays for physician services as well as drugs delivered in offices. In ophthalmology, Visudyne and Macugen have caused sharp increases in Medicare Part B expenses, and the impact of Lucentis is likely to far exceed that of Visudyne and Macugen combined. There are more than 200,000 new cases of exudative age-related macular degeneration (AMD) in the U.S. each year, (1) and we estimate that about 85% are treatable. The cost of Lucentis is about $2257 per injection, (2) and the MARINA study (3) showed benefit from monthly Lucentis injections for two years. Therefore, after one year of full market implementation, Lucentis costs in the U.S. could, in theory, exceed $9 billion.(4)

Several factors temper this figure, and, based on Lucentis sales data, it appears reasonable to anticipate at least $2-3 billion in annual U.S. sales under current conditions. Some patients require less than 24 treatments, and some retinal specialists use the PIER or PrONTO protocols. (5) Also, many providers currently treat exudative AMD primarily with Avastin. On the other hand, exudative AMD appears to be a recurrent condition, so many successfully treated patients may need additional rounds of therapy, just as many of our PDT patients have developed recurrences after initial closure of the choroidal neovascular membrane (CNVM).

To put this $2-3 billion figure in perspective, in 2006 the total Medicare Allowed Charges for all of ophthalmology was $4.77 billion. That total covers physician fees, practice expenses, malpractice Relative Value Units, and imaging. In 2004, total spending for all Medicare Part B drugs for all medical fields was about $12 billion. Compare the approximate $54,168 cost of treating one eye with Lucentis monthly for two years to the $46,326 median annual household income in the U.S. in 2005.

Avastin’s Benefits

In contrast to Lucentis’ cost, the drug cost for Avastin is only about $50 per dose. Further, many treating physicians have noted that Avastin seems to be longer-acting than Lucentis, perhaps because Avastin’s larger size impedes clearance from the eye. Consequently, many clinicians use a less frequent dosing regimen with Avastin than Lucentis.

Why Would Ophthalmologists Use Lucentis?

Although Avastin is a safe, effective, inexpensive treatment of exudative AMD, some ophthalmologists have offered the following reasons to use Lucentis:

1. Lucentis is FDA-approved for this indication.

2. Unlike Avastin, Lucentis has been studied with a randomized clinical trial, and the data for Lucentis are more long-term data than those of Avastin.

3. Lucentis may be safer than Avastin.

4. Lucentis has greater activity in vitro and Lucentis is a smaller molecule designed for better retinal penetration.

5. Physicians receive substantially more income by using Lucentis.

We’ll address each of these reasons in turn. First, most prescriptions written in the U.S. are for off-label uses. There is compelling evidence of Avastin’s safety and efficacy for CNVM in AMD based on published reports (6) and current widespread clinical use. Consequently, the federal Medicare program offers coverage for intraocular Avastin for this indication.

Second, Avastin and Lucentis are structurally very similar, and ophthalmologists’ collective short-term experience with Avastin has shown results comparable to those with Lucentis. The planned two-year National Eye Institute head-to-head study should clarify this issue.

Third, after thousands of applications, the ocular safety of both Lucentis and Avastin has been well demonstrated. In terms of systemic safety, thromboembolic events (such as angina, heart attacks, and strokes) have been the main concern. Preliminary long-term data indicate that Lucentis in the ocular dose of .5 mg (as currently prescribed) has a four-fold increased risk of stroke compared to a .3 mg dose, and this risk seems to involve primarily people with a history of prior stroke. (7) There is less long-term data on ocular use of Avastin. Among patients using Avastin systemically for metastatic colon cancer, 4.4% who had Avastin in combination with other colon cancer chemotherapies had thromboembolic events, compared to 1.9% who received various colon cancer chemotherapies and no Avastin. However, this finding is of doubtful relevance to ocular use of Avastin. The ocular dose (1.25 mg) is about 1/300th of the systemic dose (5 mg/kg) used to treat metastatic colon cancer. Colon cancer patients receive treatment every two weeks, while intraocular injections of Avastin are generally at least 6 weeks apart. Therefore, ocular Avastin results in approximately 1/1000th of the systemic exposure compared to intravenous use. The increased risk of thromboembolic events occurred only in colon cancer patients who concurrently used other chemotherapies, so the increased risk may reflect drug interactions. Finally, colon cancer often leads to a hypercoagulable state, which predisposes the patient to thromboembolic events. As a smaller molecule, Lucentis has a shorter systemic half-life than Avastin, but it is unknown whether Lucentis has less systemic toxicity. (8)

Fourth, in practice Lucentis does not appear to be more effective than Avastin. It may be that the 1.25 mg Avastin dose effectively blocks all VEGF receptors, and any additional potency of Lucentis does not confer additional effect. Lucentis’ smaller size may turn out to be a drawback, because Lucentis may clear the eye too quickly to work as well as, or as long as, Avastin.

Fifth, Medicare reimburses ophthalmologists 6% over the Average Wholesale Cost of Lucentis. Consequently, ophthalmologists who pay $1950 for Lucentis receive $2067 from Medicare, for a profit of $117 per dose given. In contrast, there is little, if any, profit generated by the $50 Medicare reimbursement for Avastin. A retinal specialist treating only 72 patients with monthly Lucentis injections, rather than treating these same patients with Avastin, will be paid an additional $100,000/yr by Medicare for the Lucentis drug. Further, retina specialist treating monthly with Lucentis, rather than treating patients with Avastin every 6-12 weeks, will likely generate additional income through injection fees.

Retinal specialists typically treat hundreds of exudative macular degeneration patients per year. While there are strong financial incentives to use Lucentis, we don’t know whether these incentives influence treatment recommendations. We do know that, for every $100,000 of “profit” paid to ophthalmologists by the 6% “margin” from Lucentis sales, the cost of the drug to Medicare, insurers, and patients is $1.76 million. The 80% Medicare portion of this $1.76 million comes from the same Medicare Part B “pot” that also pays for physicians’ medical services.

Are Medicolegal Concerns with Avastin Reasonable?

We see no reason to infer that ocular use of Avastin poses significant risk of systemic toxicity or more such risk than other anti-VEGF ocular drugs. While some providers avoid Avastin in patients with a recent thromboembolic event, (9) ocular Avastin has become a standard of care for most exudative AMD patients. A January 2007 Internet survey of the American Society of Retinal Specialists (ASRS) with 276 respondents found that 58.76% usually recommend Avastin for patients with subfoveal CNVM due to AMD when these patients have both Medicare and secondary insurance coverage (9.97% of these recommend Avastin plus PDT for such patients). For patients without secondary coverage, for whom the co-payment on Lucentis treatment is substantial, 79.20% of ASRS respondents usually recommend Avastin (2.77% of these recommend Avastin plus PDT).

What Other Factors Influence Pharmaceutical Use?

Pharmaceutical companies have always been eager to court “opinion-shapers,” academic clinicians whom their colleagues trust to offer informed recommendations. The companies readily sponsor research by these academicians, hire them as consultants, and pay them for speaking engagements. These people deny that their objectivity has been compromised, but a general review of industry-sponsored research showed a bias in favor of the sponsoring company’s products. (10) Of course, many academicians do speak their minds, regardless of corporate relationships.

Who Is Paying for Lucentis?

For many years, growth in government expenditures for health care has exceeded the rate of inflation. Such growth is not sustainable. In an attempt to control rising costs, there are federally mandated restrictions on Medicare cost increases, effectively putting health care providers in direct economic competition with drug companies for limited Medicare Part B dollars. If we cannot control pharmaceutical costs, our patients will suffer, and we physicians will likely suffer as well. While it may be more politically expedient in the short term for Medicare to cut reimbursement to physicians than to reduce benefits, rising health care costs will eventually result in larger patient premiums, increased co-payments, or reduced access to care. Ultimately, our patients will suffer to the degree that the health care system is financially crippled.

What about Patients Who Demand Lucentis?

Genentech’s media blitz has encouraged many people to request Lucentis. We tell patients that Avastin appears roughly equal in safety and effectiveness. One reason we prefer Avastin is that it may require less frequent injections, which would help reduce the risks of anti-VEGF treatment. We also note that, for people without secondary insurance, the out-of-pocket cost of Lucentis is much higher. Then we leave the choice to our patients. When using Lucentis, we generally follow the PrONTO study guidelines. That protocol often results in significantly fewer than 24 treatments for each CNVM episode.

What Do We Recommend?

1. We think it is reasonable for general ophthalmologists to ask retinal specialists who use primarily Lucentis why they choose to do so.

2. Until the NEI’s study of Avastin versus Lucentis is completed (not before 2009), we need to carefully monitor outcomes.

3. As professionals, we have obligations to society-at-large as well as to our patients. In this new era of extremely (we think outrageously) expensive drugs for macular degeneration, we should be mindful of the public-health consequences of our practice patterns.

4) As public health advocates, we should encourage legislators and regulators to remove financial incentives that might encourage physicians to treat patients with more expensive drugs.


References:

1. Postgrad Med 1998;103(5):153-64.
2. $1950 (wholesale cost) + $117 (Average Wholesale Cost mark-up) + $190 (approximate injection fee).
3. New Eng J Med 2006;355:1419-31.
4. After one year, there could be 170,000 eyes receiving monthly treatments and another 170,000 added in the second year. Each eye would receive 12 treatments per year at $2257 per treatment.
5. Ophthalmol Clin North Am 2006;19(3):361-72.
6. Ophthalmol 2006;113:363-72; Am J Ophthalmol 2006;142:1-9; Retina 2006;26:383-90.
7. Genentech “Dear Health Care Provider” [physician advisory] 1/24/07.
8. New Eng J Med 2006;355:1409-12.
9. Ophthalmol 2006;113:363-72.
10. JAMA 2006;296:996-8; Br Med J 2006;333:782-6; Br Med J 2003;326:1167-70.


Authors (All authors are retinal specialists):

February 9, 2007

Leon A. Bynoe, MD, Fort Lauderdale, FL
Randy Dhaliwal, MD, FRCSC, FACS, Augusta, GA
Joel D. Eichler, MD, Belleville, NJ
Matthew E. Farber, MD, Ft. Wayne, IN
Steve Friedlander, MD, FACS, Reno, NV
Timothy Holekamp, MD, Columbia, MO
Stephen R. Kaufman, MD, Cleveland, OH
Mike Lahey, MD, Hayward, CA
Jeffrey M. Lehmer, MD, Union City, CA
James G. Randall, MD, Missoula, MT
Scott C. Richards, MD, Ogden, UT
J. Gregory Rosenthal, MD, Toledo, OH
J. Sebag, MD, FACS, FRCOphth, Huntington Beach, CA


Avastin versus Lucentis: Why It Matters
Physicians for Clinical Responsibility
pharmeval@yahoo.com
216-283-6702
P.O. Box 201791

posted by Irv Arons @ 11:22 PM   5 comments