sfgate.com
The dilemma of a dying man
Patient sues to get unproven drug that may help defeat disease that is slowly strangling him
Bernadette Tansey, Chronicle Staff Writer Sunday, February 16, 2003
--------------------------------------------------------
Joseph Stendig is slowly suffocating to death, and he can't understand why a Brisbane firm won't let him take an experimental drug on the chance it could beat the disease strangling his lungs.
At Intermune Inc., the last thing people want to do is cause Stendig's death. But they won't give him the drug until the clinical trials the company is conducting show it's not likely to make him worse.
As Intermune cites medicine's sacred creed, "First, do no harm," Stendig finds another principle equally strong -- a dying man's right to a last shot at hope.
Already on oxygen and running out of options, the wealthy former hotel chain developer is suing Intermune in San Francisco Superior Court for refusing to sell him the unproven drug pirfenidone. Stendig says he could die of a little-understood form of pulmonary fibrosis before clinical trials conclude. And he is convinced, after reading research abstracts, that pirfenidone is his key to surviving a disease that has few treatments and no known cure.
Stendig's lawsuit puts a new twist on a tragic plot woven through the history of medical progress in recent decades.
Thousands of desperately ill patients, hearing fragments of positive news about possible remedies for leukemia or breast cancer or AIDS, often implore drug companies to release unproven remedies before they run out of time.
Companies sometimes agree to such compassionate use programs. Whether they do or not, the decision can present a public minefield of questions about their motives, ethics, fairness, funding, scientific integrity and safety standards.
Intermune executives say they can't be sure from the early test data that pirfenidone is safe enough for individuals like Stendig outside controlled clinical trials. Or that it would even do him any good.
"The first thing we don't want to do is confer harm on these patients," said Scott Harkonen, Intermune's chief executive officer. "That would be unconscionable."
Intermune's safety concerns seem meaningless to Stendig, 75, whose planned retirement of travel, golf and reading by the pool at his home on Florida's Gulf Coast has turned into an anguished countdown as his oxygen tank slowly ticks off the seconds.
Patients like Stendig with the merciless syndrome called idiopathic pulmonary fibrosis (IPF), a lung disorder of unknown cause, die an average of three years after diagnosis. Stendig, who was diagnosed two years ago, says that even if he doesn't try an unproven drug, he's not going to be safe.
Stendig's campaign against Intermune could be a sign of things to come as patients become increasingly aware of potential remedies in the industry pipeline. The news pours out through a growing network of patient advocacy groups whose Web sites post the latest scientific papers.
Companies tout the progress of drug trials to encourage investors. Many patients like Stendig, who sense that cures may arrive soon, but not soon enough for them, feel personally involved in drug company decisions.
But few patients have the resources Stendig possesses.
As he battles his disease, Stendig is deploying every weapon he gained in more than 40 years of hard work -- drive, determination, connections and money.
Most patients receive experimental drugs through clinical trials, and they must meet eligibility criteria. But there are other routes of access, and Stendig has pursued most of them.
$80,000 ON ANOTHER DRUG
He has already spent $80,000 of his own money to try one experimental drug, Actimmune, rather than join a clinical trial in which he might have received a placebo. Actimmune is also an Intermune product, but Stendig didn't need Intermune's permission to get it outside clinical trials.
Actimmune has been available for commercial sale outside clinical trials for years because it already has Food and Drug Administration approval to treat other diseases. Physicians are free to prescribe it for IPF under a long- standing option known as an off-label use. Many do, relying on preliminary results from clinical tests that, while not conclusive, are more complete than the data on pirfenidone.
Unfortunately, Actimmune didn't work for Stendig.
To get pirfenidone, which as yet has no approved use, Stendig has to rely on FDA regulations. In recent years, the FDA has accommodated demands for greater access to unapproved drugs for life-threatening diseases. Many credit the 1980s campaigns of AIDS activists for the rule changes.
Those FDA rules still leave it up to drug companies to decide which unapproved remedies to make available. Such expanded access can benefit not only patients but also drug companies, because they create a constituency for the product among doctors and patient groups just before a drug is ready to be released commercially. Companies often provide the drug free for those group releases.
Industry leaders, however, have raised a host of concerns that can weigh against the early release of some experimental drugs. Barriers include potential liability, inconclusive data and the possibility that bad patient reactions outside a carefully controlled trial could raise unjustified safety concerns about the drug.
Also, companies may make only small batches, sufficient to support their clinical trials. Smaller biotech firms often post no profit while they pour funding into the long, expensive process of seeking FDA approval.
ONLY A QUARTER WORK WELL
Patients may suffer unnecessary anguish when they can't get an unproven drug, said FDA medical officer Richard Klein. No matter how encouraging early test results may be, Klein said, only 20 to 25 percent of experimental remedies that enter clinical trials are later shown to work well.
Pirfenidone, a small-molecule compound taken orally, is in the second of three stages of human trials required for FDA approval. Intermune is testing whether pirfenidone will help prevent the fibrous scars that make breathing a struggle for IPF patients.
Intermune has no group compassionate use program for pirfenidone, but Stendig was trying to get it through a little-known FDA rule that allows single patients to obtain experimental drugs. He offered to pay the full cost and sign an agreement not to sue Intermune if pirfenidone worsened his condition.
Such offers wouldn't have swayed Intermune even if it hadn't had have safety concerns, the company said. Government ethics rules don't permit experimental subjects to sign away their legal rights, and the FDA strictly limits payment for unproven drugs, when it allows payment at all.
"It's awfully hard to say no to individual patients," said Harkonen, Intermune's CEO. "We empathize with them and their families and what they're going through."
He said the company will consider creating a group access program for pirfenidone in mid-2003, when further data about its safety and effectiveness should be available. But such a program might not help Stendig.
"If the demand is there, we might do it on a lottery system," Harkonen said.
"But it has to be fair."
PUBLIC RELATIONS DEBACLE
The fairness issue turned one compassionate use program into a public relations debacle for a trouble-plagued biotech firm two years ago. The CBS newsmagazine "60 Minutes" aired wrenching accounts by dying patients who said New York's ImClone Systems Inc. arbitrarily gave some colon cancer victims its experimental drug Erbitux while denying it to others.
A congressional committee demanded testimony on the issue from ImClone's then-CEO Sam Waksal, who later pleaded guilty to insider trading in an investigation that also cast suspicion on his friend Martha Stewart.
ImClone, now starting to get its Erbitux trials back on track after regulatory setbacks, recently announced a limited compassionate use program that will select among eligible patients by lottery.
That's the system Genentech Inc. developed in 1996, when thousands of breast cancer patients sought the South San Francisco biotech firm's then- experimental drug Herceptin. Guided by patient groups who said fairness was key, Genentech now has a formal corporate policy forbidding special treatment for individual patients -- even those with links to the company, said Heather Schwartz of Genentech's patient advocacy office.
"Regardless of financial status or socioeconomic status, it's essential that you do not have any single-patient exceptions -- for the good of ensuring that you develop the drug as quickly as possible for everyone," Schwartz said.
Stendig is not the first seriously ill patient to become distraught after a company refused access to an unproven drug, said FDA spokesman Klein. But Stendig may be the only individual patient to go to court to force the issue, he said.
Stendig filed an unusual legal action last month that, if sustained, could allow a single patient to challenge a drug firm's research priorities.
PROFIT CLAIMED AS MOTIVE
In his court suit, Stendig claims that pure profit is behind Intermune's refusal to release pirfenidone. In Stendig's view, Intermune bought the licensing rights to pirfenidone last year after realizing the drug could become a competitor to Actimmune, the company's top revenue source.
Off-label Actimmune prescriptions for IPF patients brought in at least $85 million for Intermune last year, dwarfing the nearly $10 million from Actimmune's approved uses, according to company data. About 70 percent of all Actimmune purchases are covered by medical insurance.
Stendig claims Intermune is stifling research programs on pirfenidone to prolong Actimmune's hold on the market.
Intermune executives deny Stendig's claim.
"That couldn't be further from the truth," said Dr. James Pennington, Intermune's executive vice president of medical and scientific affairs. Pennington said the company has actually accelerated the schedule for clinical development of pirfenidone as a treatment for the fatal lung disease.
Stendig also complains that Intermune is withholding access to pirfenidone because, if it were available, the company would have a more difficult time signing up clinical trial subjects for either of its IPF drug candidates.
Stending has that right, said Intermune attorney Tom Scarlett. If Stendig's suit were to succeed, Scarlett said, it could undermine the system that medicine relies on for solid proof that drugs work. And that system benefits all patients.
"If you can go to court and get the drug, why would you enter a controlled drug study where you might get a placebo?" Scarlett said.
FEW CAN PAY THE PRICE
Stendig said that concern shouldn't trouble the drug industry because most people couldn't afford to pay out of pocket for an unapproved drug.
"If you are not one of the fortunate few, as I am, who can lay out $50,000 a year to buy the drug -- in a clinical trial, you've got a 50 percent chance of getting it, and a chance it will do you good -- you'll sign up," Stendig said.
In spite of his illness, Stendig speaks with the vigor of a man who was playing tennis five times a week before his diagnosis. From his home in Bonita Springs, Fla., where he lives with his wife, Eileen, Stendig has expanded his campaign for pirfenidone.
Since filing his suit, he has founded a not-for-profit foundation for IPF patients. Its Web site details his complaints against Intermune, which he has also distributed over a major business wire.
Although Stendig is convinced of pirfenidone's value, a Bay Area lung disorder specialist said the early studies so far show no dramatic improvements.
"It's not like the company is withholding a cure for this disease because the data are not there yet," said Dr. David Morris, an assistant professor of medicine at UCSF who has no financial ties to Intermune.
SUIT MAY BE DISMISSED
Stendig's suit, which charges Intermune with unfair business practices under the California Business and Professions Code, may be dismissed at an early stage, said Paul Lombardo, a former California health care attorney. Lombardo, a University of Virginia professor of research regulations, said he knows of no California provisions that would support Stendig's claim.
"I'm not sure what's in it for the plaintiff but publicity, but it's his money," Lombardo said.
Even if Stendig could show that Intermune sidelined a potential drug to avoid competition, he might lack standing to bring such a suit, Lombardo said. To win, he'd have to prove his claim that his health is declining because he can't get pirfenidone. To do that, he'd have to prove that the experimental drug works. That may only be possible if Intermune can complete controlled clinical trials.
If his suit fails, Stendig has a backup plan to get pirfenidone. Although Intermune controls U.S. and most worldwide rights to the drug, a Japanese firm has the license to sell it in Japan, Korea and Taiwan. That company is already applying for regulatory approval in Japan. Stendig hopes it'll come through this summer.
Would he fly there if he had to?
"Hell yes," Stendig said. "I'd be on a plane tomorrow morning."
--------------------------------------------------------------------------------
ROUTES TO PATIENT USE OF EXPERIMENTAL DRUGS
Clinical trials: Patients must meet eligibility criteria and may receive a placebo.
Off-label use: Doctors can prescribe a drug for use against one disease if the FDA has approved it to treat another. Safety has been studied, but effectiveness is not yet proven.
Group expanded access program: Experimental drug is made available to a limited group of patients, usually when tests for safety and efficacy are well advanced.
Single-patient access: Company may release an experimental drug to individuals whose doctors can follow safeguards similar to those in clinical trials.
E-mail Bernadette Tansey btansey@sfchronicle.com. |
