Healthy Skepticism Library item: 14320

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Publication type: news

Herper M.
Patient Power
Forbes Magazine 2008 Sep 15
http://www.forbes.com/healthcare/forbes/2008/0915/070.html

Full text:

If you are told you have an incurable disease, you might be motivated to help find a cure.
Every crash and thump of Emily Schaller’s drumsticks is a medical victory. The 26-year-old rock ‘n’ roller suffers from cystic fibrosis, which fills her lungs with bacteria-infested mucus. If she had been born 30 years earlier, she probably would have died before she finished high school. Instead, she’s “playing my guts out,” she says, hammering out licks she learned from listening to Mötley Crüe and AC/DC. Her all-woman band, Hellen, has played at almost every club in Detroit since she and four friends taught themselves to play five years ago.

Schaller keeps up a grueling daily regimen. She runs 25 miles a week, spends hours doing physical therapy and swallows 40 pills a day. But she gives much of the credit for her active life not to her diligence but to a 53-year-old patient advocacy group, the Cystic Fibrosis Foundation. “They’re the reason I’m alive,” she says.

The CF Foundation was the first patient charity to do something radical: pay for drugs to be invented and tested in people. It funded the first clinical trials of an aerosolized antibiotic Schaller has been breathing in for a decade. It has been testing a saltwater mist that Schaller says is “the best thing ever” for clearing out her lungs. Last year she was in a study of a promising experimental drug the CF Foundation paid to invent. Approval of another CF Foundation-backed drug, from Gilead Sciences, is expected any day. Over the past 20 years the CFF has put $188 million into research at drug companies, and it is currently involved in human studies of 33 drugs.

“The impact is huge,” says Norbert Bischofberger, chief scientific officer at Gilead Sciences, the third-biggest biotech by market capitalization. Gilead bought a CFF-backed company in 2006 for $365 million, and he says the foundation’s stamp of approval gives companies more credibility with investors. “If they have looked at it, and they have funded it, it must be something worthwhile.”

Inspired by the CFF’s success, patient groups with an entrepreneurial bent have become the drug industry’s new power brokers. Medicines for blood and bone cancers have reached the market faster because of their efforts. A hundred more patient-group-backed drugs, one-twentieth of all the medicines in development, are in human clinical trials for Parkinson’s, diabetes, muscular dystrophy and a litany of cancers. These patient power brokers will give drug companies $90 million this year, 13 times as much as in 2000, according to Thomson CenterWatch, a research firm that analyzes clinical trials. The Leukemia & Lymphoma Society has 50 drugs in development, including 11 in clinical trials. The Multiple Myeloma Research Foundation is working with 30 drugs, up from none in 2000, and just recruited a cancer-drug executive from Bayer to help run its effort. The Juvenile Diabetes Research Foundation is testing 18 drugs with biotech companies.

Patient power brokers assemble teams of academic scientists to help identify the best medicines to fund. They pay for the invention of new drugs and for clinical trials of medicines making their way to the market. They grease the skids for clinical trials, too, by assembling networks of doctors and patients who want to participate. By becoming a one-stop source for expertise and research about their disease, these patient groups can use as little as a few million dollars in funding to shift the priorities of the drug industry.

The patient groups are filling a void in drug research created by the industry’s legitimate fear of failure. Biotech executives dread what they call “the valley of death,” the period of time between a drug’s conception in a lab and its first clinical trial. For every 10,000 would-be medicines chemists create, only one makes it to market. But if a drug has already been through enough tests in cell cultures and lab animals to justify starting clinical trials, the odds of success have risen to one in nine. Put the substance through early clinical trials with a few dozen patients, and the odds jump to one in six. At some point a drug for even the most uncommon disease becomes every bit as appealing to drug companies as an untested potential heart treatment or impotence pill.

“If pharma doesn’t do it anymore, somebody else has got to do it,” says Rainer Fuchs, a vice president at Biogen Idec who runs its in-house biotech incubator.

Patient advocacy burst onto the national scene in the late 1980s when protesters demanded and got faster approval of hiv drugs, earlier access to experimental medicines and more government research money. But that success required sustained efforts from thousands of disease advocates. More typical today: small groups engaging in quiet lobbying.

Most of the thousands of patient advocacy groups in the U.S. still focus on raising awareness or begging for more federal money. Susan G. Komen for the Cure has spent $629 million on education about and screening for breast cancer since 1982, twice as much as on basic research. In the last year Komen, taking a page from the patient power brokers, has refocused its research efforts to try to get treatments to market faster.

Some patient groups can take their mission a little too far, or get too cozy with drugmakers. An analysis in the Journal of the American Medical Association of 44 groups that argued for the approval of new treatments at Food & Drug Administration meetings found that 73% received funding from drug companies. “It has evolved into just another way for the industry to get its message across,” says Peter Lurie of Public Citizen, which conducted the study. In 2007 the Boston Globe reported that the Breast Cancer Resource Committee was giving a third of every dollar raised to its chief executive. Most of the money came from corporate donors; the group, which no longer has a Web site, spoke out in favor of silicone breast implants and was quoted in a Pfizer press release.

“You get a broad range from hoaxes, charlatans and self-centered megalomaniacs to extraordinary altruism and everything in the middle,” says George Demetri, an oncologist at the Dana-Farber Cancer Institute in Boston, Mass.

The appearance of too much coziness can backfire for companies. The Max Foundation in Edmonds, Wash. was one of the biggest defenders of Novartis when the Indian government said last year that the cancer pill Gleevec doesn’t deserve patent protection. But the Max Foundation helps poor patients get the $3,000-a-month cancer pill, with generous support from Novartis itself. The defense fell on deaf ears. As part of his war with the drug industry, Senator Chuck Grassley (R—Iowa) has been pushing companies to disclose more about their payments to foundations. Eli Lilly and GlaxoSmithkline have voluntarily complied.

In May 2007 the FDA rejected Dendreon’s prostate cancer drug Provenge even though an advisory panel had voted to approve it. The FDA was swayed by some prominent cancer researchers who wrote letters saying the data were lousy. When the letters were leaked to Paul Goldberg, editor of The Cancer Letter, the doctors were so besieged by angry e-mails they took bodyguards to cancer meetings. One group, called CareToLive, sued the FDA. It tried to serve Goldberg with a subpoena and instead wound up confronting his teenage daughter. A judge said the group’s behavior was “meant to harass” and ordered that Goldberg should be paid $6,000 to cover legal costs. (The lawsuit against the FDA continues.) The group also organized a protest outside the FDA. It says its tactics are “much more tame” than those of previous disease advocacy groups. But the group has alienated doctors who research cancer treatments. Many of them still doubt Provenge.

“Especially in prostate cancer, I have seen a bunch of survivor groups that are not very interested in basing things on science and are basing things on emotion,” says Otis Brawley, chief medical officer of the American Cancer Society. Brawley has come to see how the better patient groups evolve. They often go from brashly demanding cures to learning that some treatments that seemed to help, like bone marrow transplants for breast cancer, turned out to do harm.

The new generation of patient power brokers sprang from the frustrated mind of CF Foundation President Robert Beall in the mid-1990s. A biochemist by training, Beall had been funding discoveries for a decade, including uncovering the CF gene itself. The gene makes a protein that helps move water and salt into and out of cells. Defects in it cause the pancreas to dissolve in infancy, necessitating a lifetime on pig-derived digestive enzymes and vitamins. Boys become infertile because they lack the tubes that carry sperm from the testes. Hardest hit are the lungs, which fill with mucus that can cause deadly pneumonia.

But only 70,000 people have CF worldwide, too few to lure drug companies to develop treatments. Beall decided to fund pharmaceutical firms directly to get them interested.

It started with an inhaled antibiotic called tobramycin. The CF Foundation spent $1.8 million on the initial clinical studies of the medicine, resulting in the creation of a biotech called PathoGenesis; Beall sold the company the foundation’s right to a royalty on the drug. PathoGenesis was bought for $700 million by Chiron in 2000, which was bought in turn by Novartis for $5 billion in 2005. Now tobramycin, approved in 1997, generates $270 million a year and is a bedrock of CF therapy for patients like Schaller. “We have a commercially available drug now because we took that early risk,” says Beall.

Beall was emboldened, but most companies he approached with funding weren’t interested. A tiny biotech called Aurora Biosciences took Beall up on his offer and tried to create a drug based on the CF gene.

Aurora got bought by Vertex Pharmaceuticals of Cambridge, Mass. in 2001 for $600 million. The CF drug wasn’t a big factor in the deal, but it became important to Vertex. Employees felt “part of this mission,” says Vertex Chief Executive Joshua Boger. “I couldn’t stop this program if I tried.”

Earlier this year the drug showed stunning preliminary results. Not only did it improve patients’ lung function, it lowered the amount of salt in their sweat, a sign that it may combat CF at its biological root. “If kids don’t have lung damage, they might take this and go their whole lives without any symptoms,” says William Elder, a 21-year-old patient in the study.

In 2005 doctors in Australia noticed that surfers with cystic fibrosis had a lot less muck in their lungs. Was salty ocean spray the reason? The CFF spent $1.2 million to test the theory. Now one in five cystic fibrosis patients inhales a supersalty mist.

The early successes of the Cystic Fibrosis Foundation were just about the only lifeline Kathryn Giusti had when she was diagnosed with multiple myeloma in 1996. At 37, she was a marketing executive at Searle (now part of Pfizer), planning the launch of the arthritis drug Celebrex, and she had a 1-year-old daughter, Nicole. Sixty percent of myeloma patients are dead within five years.

Giusti founded the Multiple Myeloma Research Foundation in 1998 with the goal of using her drug industry know-how to get treatments developed. “I wanted to go out fighting,” Giusti said in a speech to thousands of oncologists in 2003. “I just wanted Nicole to remember me. If I lived until she was 5, maybe she would.”

An opportunity came in 2000. Julian Adams, a chemist at Millennium Pharmaceuticals, came to a foundation dinner meeting Giusti had organized at the Boston Hilton with stunning data on a drug he had invented. “I was blown away,” Giusti says. The other doctors in the room suggested canceling the event and turning it into a clinical-trial-planning session. The best minds fighting myeloma worked into the night in the Hilton ballroom and designed the clinical trial that got Velcade, a life-extending treatment, approved by the FDA in 2003. If Giusti hadn’t happened to have gathered all the experts in one room, that planning session would have required dozens of e-mails, phone calls and cross-country trips. Giusti took Velcade in 2005 but stopped after a bone marrow transplant.

Giusti’s group is now a force to be reckoned with. It has an annual budget of $23 million and has organized a network of 15 cancer centers that test myeloma drugs. In the past year it has started 15 clinical trials. It persuaded one company, Semafore Pharmaceuticals, to test a drug in myeloma by offering it access to the network. Earlier this year Giusti hired away Bayer executive Susan Kelley, who had overseen the development of the kidney and liver cancer pill Nexavar, which should have sales of $600 million this year. “I desperately wanted to attract high-level talent,” says Giusti. “It took me ten years to be at a point where a Susan Kelley would join this [foundation].”

In 1997 Chicago real estate investor Robert Rosen was diagnosed with something he’d never heard of: a myeloproliferative disorder. These blood malignancies afflict 200,000 Americans. They’re caused when blood-forming stem cells inside the bone marrow go into overdrive. Patients are at high risk for potentially deadly blood clots, often have itching all over their bodies and, in a small percentage of cases, develop killer leukemia. The main treatment is medieval: bloodletting.

Rosen heard through the grapevine at his clinic that Robert Pritzker, the Chicago billionaire industrialist, was also a patient there. He had met Pritzker a few times in business contexts. Rosen called him with trepidation.

Pritzker, it turned out, had almost been killed by his blood cell proliferation in 1989 when a clot blocked off a blood vessel that runs between the liver and the small intestine. He was hospitalized for his mysterious pain, and late at night fainted and hit his head. The medical resident caring for him got on the phone to his dean and insisted that his patient needed surgery right away. He was right. Much of Pritzker’s intestine was gangrenous and had to be removed. Pritzker named a professorship at the Pritzker School of Medicine after the medical resident.

Pritzker agreed to help Rosen found the MPD Foundation, offering up a five-figure sum. “At least I know we won’t do any harm,” he said. At first the foundation wasn’t quite sure what to do. Its early success was to use small grants to keep young scientists from abandoning their research on the disease.

One of the first grants was to find the gene that causes the malignancy. But the discovery came from elsewhere. Gary Gilliland, a hematologist at the Dana-Farber Cancer Institute, used a Web discussion board to recruit hundreds of patients willing to give him genetic samples. He found that an acquired mutation in a gene called JAK2 causes 90% of myeloproliferative cases. (Pritzker, ironically, is one of the 10% without this mutation.)

Two other researchers made the discovery at the same time. It was a triumph but also a waste. Why had all the smartest minds in myeloproliferative research been doing the same thing, without working together? “As an entrepreneur, I saw competitors work together,” says Rosen. “I didn’t see that in medical research.”

Rosen went to Gilliland and two of his rivals with a deal: He’d give them each $250,000 a year if they would share their data and focus on making new drugs. Gilliland said yes, but sharing his research before publication didn’t come easy. The first time the group of researchers met, he piped up with research showing that mutations in genes related to JAK2 could also cause the disease. That meant that JAK2-blocking drugs might work for patients like Pritzker, too. He was terrified as he showed his study of 50 patients to his teammates. But although one of them was able to replicate this work in an 1,100-patient database of tumor samples, Gilliland still got to publish first, keeping his scoop. The larger study followed in another scientific journal.

Now there are seven anti-JAK2 drugs in clinical trials. Gilliland, because he is funded by the Howard Hughes Medical Institute in Washington, D.C., isn’t allowed to take money from drug companies. But Rosen’s foundation can pay his lab for its work with companies such as Exelixis and TargeGen that are testing anti-JAK2 drugs.

Scott Johnson, a 52-year-old multiple sclerosis patient who served as chief executive of three startups, is influencing the direction of early drug research for his disease. He founded the Myelin Repair Foundation in 2001 to focus doctors on the idea that myelin, the coating that is stripped off nerves by ms, could be regrown. He says he can prove his theory for $25 million ($23 million raised to date), thereby laying the groundwork for a new generation of drugs. His foundation has come up with a plan to fund scientific projects that will identify biological targets on which drugs can be based.

“For the past 30 years I keep hearing about breakthroughs, but none of them pan out,” says Johnson. “Academics don’t have an appreciation of what it takes to take a discovery and move it into the clinic and to patients.”

Isis Pharmaceuticals in Carlsbad, Calif. is working to invent a drug for Huntington’s chorea. It wouldn’t be doing so were it not for the Cure Huntington’s Disease Initiative, a group that in 2004 turned itself into a biotech called CHDI. “The realization was you could do a better job having a biotech company,” says CHDI Chief Executive Robert Pacifici. “Although we’re interested in basic research, we want to see if we can solve this by preventing this disease.”