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:

Avastin: A New Hope for Treating AMD (January 2006)

Avastin Update: Medicare not Likely to Cover its Use (March 2006)

Avastin Update II: AAO supports Medicare Coverage for Off-label Avastin Use (April 2006)

ARVO 2006: A Further Update on Both Avastin and Lucentis for Treating AMD (May 2006)

Avastin/Lucentis Update 4: FDA Approves Lucentis for Treating Wet AMD (July 2006)

Avastin Update 5: NIH Considers Comparing Lucentis and Avastin (August 2006)

Avastin/Lucentis Update 6: Latest Results Published in NEJM and Another Call for a Trial Between Them (October 2006)

Avastin/Lucentis Update 7: BREAKING NEWS – NEI/NIH Will Fund Comparative Study (October 2006)

Avastin/Lucentis Update 8: A Report of the Latest News from the 2006 AAO Meeting (November 2006)

Avastin/Lucentis Update 9: A Disturbing Report about the Upcoming Trial Between Avastin and Lucentis (December 2006)

Avastin/Lucentis Update 10: A Review of the Current Status of These Drugs for Treating AMD (January 2007)

Avastin/Lucentis Update 11: A White Paper on Why Avastin vs Lucentis Matters (February 2007)