Ride For Life: Diseases without clout

The disease slipped stealthily into Augusta Lodding's life about 12 years ago.

"It was a very gradual thing," said Lodding, 66, of Moriches. "I started noticing when I was combing my hair my head was turning to one side -- and I wasn't turning it."

After three years of pain and stiffness, Lodding consulted a doctor, who gave her a tongue- twisting diagnosis. She had spasmodic torticollis, a movement disorder that causes abnormal twitching and twisting of the muscles in the neck, making it list to one side.

Rakshand Nafisi of Brooklyn's Borough Park was forced to leave her pill-packing job in a warehouse in 2001 because of the disorder.

"My neck started moving to the right all by itself," said Nafisi, 43.

Spasmodic torticollis, a form of dystonia, or movement disorder, afflicts more than 90,000 people in the United States -- a relatively small number compared with more common illnesses, such as diabetes or heart disease. Because rare illnesses are often neglected by medical research, they are referred to as orphan diseases.

Trouble with funding

About 25 million Americans suffer from more than 6,000 such rare and puzzling diseases, each of which affects fewer than 200,000 people. Some cancers belong in the orphan category: One, mesothelioma, is often caused by asbestos contamination of the lungs. And some orphans are well-known disorders, such as Lou Gehrig's disease.

Finding treatment can be difficult because the diseases, with a small community of patients, don't have the clout and money-making potential to prompt pharmaceutical research.

But two years ago, Congress passed the 2002 Rare Diseases Orphan Product Development Act, authorizing $25 million in annual spending by the Food and Drug Administration on research for new drugs for these illnesses. Despite the spending authorization, Congress has yet to provide the money. And for 2004, the FDA's budget for orphan drug research stands at about $13.2 million.

Rep. Mark Foley (R-Fla.), sponsor of the 2002 law, said last week Congress has dragged its feet, concentrating on more prominent issues while neglecting funding for orphan drugs. Now, Foley said he's initiating "a full- court press" to persuade Congress to come up with the money.

Orphan disease advocates are speaking out, too, accusing Congress of reneging on its promise. Last week, Diane Dorman, vice president for public policy for the Connecticut-based National Organization for Rare Disorders, said Congress had broken an even-earlier promise.

"Congress made a commitment to the rare disease community 20 years ago when they passed the Orphan Drug Act to ensure that research would move forward and products would be developed for rare diseases," Dorman said. "And in my opinion, they have broken that promise."

Dr. Marlene Haffner, director of the FDA's orphan products development office, said more money allocated would mean more research for these diseases.

Without funding, she said, "we can't get as many drugs out. We worry that we're letting patients down."

High price to produce drugs

The drug companies are one target of the advocates' wrath.

"The pharmaceutical industry, when it decides where to put their money, they're going to look at very common diseases," said Abbey Meyers, president of the National Organization for Rare Disorders.

Jeff Trewhitt, a spokesman for the Pharmaceutical Research and Manufacturers of America, an industry group, said that cost has indeed contributed to the dearth of "orphan drugs."

"A pharmaceutical or biotechnological research company, as it decides its research portfolio, is always cognizant of the fact that the average cost of researching one new drug is on average more than $800 million," Trewhitt said, noting some companies never recoup the full cost of their research.

At last count, the FDA had approved 252 such orphan drugs. They're being used to treat about 12 million Americans, according to Haffner. About 50 percent of the drugs are geared for use in children.

To entice pharmaceutical companies to develop orphan drugs, the FDA gives them exclusive marketing rights for seven years, along with tax credits and other financial incentives. Such exclusivity can be important, especially to companies that develop biotech drugs, which often have a tough time being patented, Haffner said.

Additionally, if a company finds a rare-disease use for a drug whose basic structure was developed years ago for another purpose, the FDA can prevent other companies from marketing it to treat that rare disease, even if the company lacks patent protection.

Often, the price for orphan drugs can be high. Some patients pay as much as $200,000 a year, largely because the cost of research on drugs for a small number of people can't be spread over a large market.

'In good hands'

But once in a while, serendipity steps in.

Researchers weren't searching for an orphan drug when they began working with Alimta, an Eli Lilly and Co. product; they were testing it on various cancers. They were stunned to find that, when combined with another chemotherapy agent, it had a marked effect on malignant pleural mesothelioma, a rare lung cancer linked to exposure to asbestos.

Last month the FDA approved Alimta as the first drug designated specifically for mesothelioma. When used with Cisplatin, another cancer drug, Alimta was found to inhibit enzymes that mesothelioma cells depend on and has extended the lives of some patients as much as three years beyond what could be expected with conventional chemotherapy, said Dr. Nicholas Vogelzang, who led the clinical trials and is director of the Nevada Cancer Institute.

"It's an unmet medical need," Vogelzang said. "There was no competition."

Frank Cettina, 80, of Center Moriches was diagnosed with mesothelioma in January and is the first Long Island patient to receive Alimta, according to his oncologist, Dr. Robert Weiner of Great Neck. Cettina was born in Astoria and worked as a general contractor in Queens and Brooklyn for years, tearing up old floor tiles, insulation and pipes that he said contained asbestos.

"I'm gung ho and I'm in good hands," said Cettina as he received his second dose of Alimta last week. The 15-minute intravenous Alimta drip was administered along with a six-hour drip of Cisplatin. Cettina said he experienced mild nausea after his first treatment.

Making financial sense

Alimta is "impressive because for the first time we have something that improves survival for this very difficult disease," said Dr. Bhoomi Mehrotra, a hematologist-oncologist at Long Island Jewish Medical Center who referred patients to the Alimta trials.

Lilly spokeswoman Judy Kay Moore said each combined treatment of Alimta and Cisplatin costs about $4,100 and that Medicare and insurance policies should cover most of it. Lilly provides the drug to patients who have neither the money nor the insurance to pay for it, Moore said.

Some companies, such as Genzyme Corp. of Cambridge, Mass., have decided that targeting orphan diseases could make sense financially. Genzyme anticipates total annual revenues of $2 billion in 2004.

Last year, the FDA approved one of Genzyme's orphan drugs: Fabrazyme, which can reverse kidney disease caused by Fabry disease, a metabolic genetic disorder that affects both men and women, although men usually suffer more severe symptoms, according to Genzyme spokesman Bo Piela.

Fabry disease usually reveals itself in the teenage years as burning sensations in the hands and feet. In the 30s and 40s, Fabry can cause kidney failure and early heart attack and strokes.

Piela said only about 5,000 people worldwide have Fabry disease and that Fabrazyme helps prevent its progression by replacing a missing enzyme with an artificial version. That helps remove a certain fat from blood vessels in the kidneys, preventing kidney failure, heart attacks and strokes.

But Fabrazyme costs about $180,000 annually for the intravenous infusions patients receive every two weeks -- for life. Most pay with medical insurance or Medicare, and Genzyme provides it free to those who can't afford it.

Dr. Richard Finkel, a pediatric neurologist at The Children's Hospital of Philadelphia, is enthusiastic about Fabrazyme but said its cost can be financially devastating.

"Suppose you have an insurance company that will pay up to 80 percent," Finkel said. "You still have to come up with 20 percent" of $180,000.

Finkel said Fabrazyme's side effects can range from itching, flushing and chills to severe breathing problems.

Orphan drug Botox

But there are some orphan drugs that have few side effects, don't cost a fortune and help make patients more comfortable.

Lodding, the Moriches woman with spasmodic torticollis, is receiving injections of Botox, an orphan drug more often heralded as a wrinkle eraser. Lodding said Botox helps relieve the pain and twisting in her neck.

"It's about 70 percent back to normal," she said.

Botox was originally used for spasmodic torticollis and blepharospasm, rare eye muscle twitching that can leadto blindness. Later doctors discovered Botox erased wrinkles, too. It was Dr. Andrew Feigin, director of the movement disorders center at North Shore University Hospital in Manhasset, who recommended botulinum toxin type A -- Botox is a brand name -- for Lodding.

Feigin said patient reaction varies. "Itdepends on the movement disorder the person has," Feigin said. "For blepharospasm and spasmodic torticollis, 90 percent of people have a positive response."

Botox contains the toxin that causes food poisoning but is safe when purified for medical use.

Ellen Flynn of Garden City South also sees Feigin for botulinum shots for torticollis.

"It made me much more functional with much less discomfort," Flynn said.

Botox injections can be costly -- hundreds or even thousands of dollars for a treatment, depending on the size of the muscle treated. Insurance generally covers the cost when the drug is used for noncosmetic reasons.

As for Nafisi, the Brooklyn woman who also suffers from spasmodic torticollis -- she too is getting Botox injections but is not yet back to work.

"The pain has not disappeared but it's a little bit less," Nafisi said. "My head doesn't tip over anymore."