COLUMN ONE : A Lottery With Very High Stakes : Two friends united by MS are among patients seeking a scarce but promising new drug. Sharon drew No. 319, Alison 59,814. Such inequities frustrate both the lucky ones and those who can only wait and hope.

By SHERYL STOLBERG

Jan. 6, 1994 12 AM PT

TIMES MEDICAL WRITER

They are sisters in spirit, Sharon Fuhrman and Alison Caldow. They guard one another’s fears and secrets, finish one another’s sentences. They giggle at quirky British television shows, grow melancholy at poignant ballads and share a zest for what Sharon calls “artsy, intellectual kind of stuff.”

But common likes and dislikes are not what brought these women together. Sadly, their friendship is rooted in a crippling disease--multiple sclerosis--that is slowly stripping them of control over their bodies and minds. Already, MS has pushed Sharon into a wheelchair. It takes all of Alison’s strength just to walk.

Now, fate binds them in another way: the lottery.

This was no ordinary lottery, nothing as simple as spinning the Fantasy Five or as serendipitous as a quick pick from the computer at 7-Eleven. No, this was a gamble with much higher stakes, a drawing for a brand-new drug--the first new treatment for multiple sclerosis in a quarter-century, and the first ever to attack the disease itself, rather than simply easing its symptoms.

The drug is called Betaseron. It is not a miracle worker. It won’t cure multiple sclerosis. It won’t reverse damage already done. But it does seem to keep MS patients from getting worse--something no other medicine has done.

But Betaseron is expensive--$10,000 a year--and the government-funded Medicare program, as well as some private health insurance plans, won’t cover it. More critically at the moment, there is not enough of it to go around.

Thus, the lottery, run by Berlex Laboratories, a Richmond, Calif.-based company that created Betaseron. The rules were simple: The first 12,000 would get the drug right away, and another 55,000 would wait until more supplies become available.

The results came back a couple of months ago, and the close friends could not have been further apart.

Sharon’s number is 319. She started taking Betaseron the week before Christmas. Alison drew 59,814; she must wait at least until mid-1995. Kismet had dealt these women a bittersweet hand, and the lucky one found herself grieving.

“I felt so bad for her,” Sharon says. “I know how much it means to her to stop this thing while she can still walk. Every time she gets a new twinge, I hurt for her. I remember when I went from her stage to this stage, and I hate to see that happen to her. I almost at one point thought maybe it would be better if she got it. But I can’t fix that.”

If Alison is jealous or disappointed, she refuses to show it. “Just because I have a high number I am not going to give up my positive attitude,” she insists. “Life goes on. It went on before Betaseron. It will go on after it. . . . I just feel for the person who has a higher number than I do, and who needs it more.”

The story of these women, who befriended one another through a support group in the Southern California high desert town of Hesperia, illustrates the plight of thousands of multiple sclerosis patients across America who are pinning their dreams on a drug that, either because of high cost or limited supply, is tantalizingly beyond their grasp.

One angry father organized a massive letter-writing campaign when his 16-year-old son drew a number above 50,000; he is threatening to sue Berlex if the teen-ager doesn’t get the drug by April. Says one tearful, frustrated patient: “They have produced this wonderful drug and are hanging it out in front of our noses, like a carrot in front of a donkey.”

This is also the story of high-tech medicine, and how a pharmaceutical company poured 10 years into developing a drug that it now must price high enough for shareholders to see a return. Without dramatic advances in genetic engineering and the willingness of investors to risk hundreds of millions of dollars, Betaseron would never have been possible. Now, Berlex officials say, it is time to pay these people back.

“This is not an unreasonable mechanism for funding research,” says Dr. Jeffrey Latts, the company’s vice president for clinical research. “That’s how it works.”

And finally, it’s the story of the nation’s quirky, patchwork health care system--a system fraught with loopholes.

Berlex is offering financial aid to low-income people who entered the lottery but lack insurance, and in some cases is even giving away Betaseron. But that doesn’t help people who are insured but whose carriers won’t cover the drug. (Sharon’s does.) Medicaid, the federal insurance program for the poor, pays for Betaseron. Medicare, which provides coverage for an estimated 50,000 elderly and disabled MS patients--including Alison--does not.

The reason? Betaseron is taken by self-administered injection, in much the way diabetics give themselves insulin. That makes it an outpatient drug, and Medicare does not cover outpatient prescriptions. But if a doctor gave the shots, they would be covered.

“In truth, our big problem is the terrible, outrageous, abominable state of health insurance in this country,” says Martha Keys, chief spokeswoman for the National Multiple Sclerosis Society. “This is why we so desperately need comprehensive health reform.”

As a former congresswoman from Kansas, Keys once had a hand in shaping health policy. Now, she is on the other side of the fence, lobbying her former colleagues to make an exception to the Medicare rule about Betaseron.

“Just think about trying to get $10,000 out of your income next year,” she says. “We have people who have called in and said, ‘Look, I’ve increased the mortgage on my house so I can get Betaseron for a year, but what am I going to do after that?’ ”

Betaseron means so much to people with multiple sclerosis because it is their greatest hope yet in battling an illness that strikes quietly, often slowly, but ultimately with devastation.

An estimated 350,000 Americans are afflicted with MS. It most often hits between the ages of 20 and 40, and strikes twice as many women as men. Sharon, who just turned 50, has had MS since she was 33. Alison, 36, received the diagnosis seven years ago.

The disease is not considered fatal, but it is insidious, wearing the body down over time. Its symptoms are debilitating--blindness, paralysis, bladder dysfunction, fatigue, loss of memory, slurred speech, muscle spasms--and they vary greatly from patient to patient.

MS is like a thief. It has a ruthless way of robbing people of what they cherish most.

Sharon once had a beautiful singing voice; as recently as three years ago, she had a job delivering singing telegrams. Now she speaks in a computer-like monotone, the words trickling out at an achingly slow pace. She is fond of baking, but following recipes is difficult; her mind can’t accumulate information. She loved to write, especially letters, but she can’t string sentences together quite the way she used to.

She misses being able to plan. She is a widow whose children are grown, and she had designs on moving north, to Washington, where the air is finer and the scenery prettier. Then reality hit.

“I don’t know what I’m going to be like in a year,” she says. “If I can’t take care of myself, what am I going to do way up there among strangers? You don’t want to think the worst, but it would be nice to know what’s in store. That’s the trouble with this stupid disease. You can’t plan.”

At a glance, Alison looks healthier than Sharon. But appearances deceive. Her gait is unsteady; she must hold onto walls and furniture when she does not use her cane. Her hand quivers when she writes a check. She wears a size six shoe, but her sneakers are sevens; she buys them big so she can slip them on without having to fiddle with the laces. Her shirt is a pullover; like most people with MS, her fingers lack the dexterity for buttons.

Alison’s passion was riding horseback, but multiple sclerosis forced her to give it up. She couldn’t get up on her horse anymore, and she didn’t have the energy to groom her. Recently, she sold the animal, a Morgan Arabian named Sable, to a rancher who planned to offer rides to disabled children. Thinking about it makes her cry. But her real regret is that she and her fiance will never have children; she says having a mother with MS would be too big a burden on a child.

“I grieve an awful lot,” she says, wiping her eyes, “for things I have no control over.”

Why she and Sharon are ill is a mystery. Nobody knows what causes multiple sclerosis.

Along with rheumatoid arthritis and lupus, MS is one of a series of “autoimmune disorders” in which the immune system runs amok, mistakenly attacking the body. In MS, the central nervous system--the brain and spinal cord--is the target.

The disease destroys myelin, the protective sheath surrounding nerve fibers that transmit messages to the body. Myelin works like insulation on an electrical wire. Without myelin, nerves short-circuit. Their messages get scrambled, and the brain can’t tell the body what to do.

MS wreaks its havoc in sudden flare-ups, or “exacerbations”--episodes in which the symptoms become excruciatingly severe. These attacks have no pattern; they may happen every three months or every three years. Alison had her last one in September. She woke up choking, unable to control her ability to swallow.

With each flare-up, patients lose a little more ground. They often talk wistfully about “coming back” from an attack, as though they have gone on a voyage and left a part of themselves behind.

“When I come back,” Alison says, “there is always something different wrong with me. Prior to this one, predominantly my left side was affected. Now it is both the left and the right.”

There are drugs on the market that ease the symptoms of MS, and most patients can rattle off their tongue-twister names: Baclofin for muscle tightness and spasms. Amantadine for fatigue. Pro-Banthine for bladder control. Carbamazepine for the burning, shooting pain that comes with MS. Methylprednesilone and other steroid treatments to make walking easier and relieve double vision.

But there has never been a drug that attacked MS directly, one that actually prevents exacerbations from occurring. Until Betaseron.

“This is the first drug ever that has changed the natural history of this disease,” declares Dr. Kenneth Johnson, a University of Maryland neurologist who participated in the clinical trials of Betaseron. “This is very promising.”

But the discovery did not happen overnight.

The drug is a genetically-engineered form of beta interferon, a naturally occurring protein that the immune system uses to fend off viruses. Because of its immune properties, scientists had high hopes for Betaseron. But they fumbled around for a decade before they figured out a good use for it.

Berlex tried the drug on just about everything--on cancer of the kidney, colon, lung and brain, on hepatitis and on viral infections, as well as on multiple sclerosis. There have been 75 clinical studies of the drug. All flopped except two--the ones involving MS patients.

“There were a lot of people who were very frustrated by the process,” says Latts, the company’s director of clinical research. “These products don’t come out of the laboratory with a sign on them saying, ‘This is good for multiple sclerosis.’ ”

In 1988, after a small pilot study, Berlex began testing Betaseron on 372 MS patients in the United States and Canada. All were still walking, and all suffered from “relapsing remitting” as opposed to “chronic progressive MS,” an extremely disabling, late stage of the disease.

The results were impressive but not overwhelming.

Patients who got the drug had 35% fewer attacks than those who got a placebo and half as many serious exacerbations. But what Johnson and other neurologists found particularly compelling were the magnetic resonance images of the subjects’ brains.

MRI scans of placebo patients showed a 20% increase in damaged myelin. Patients who got Betaseron showed no new damage at all. “That is the promise of this drug,” Johnson says, “that it is going to make a difference in the accumulating neurological damage, in the need for canes and wheelchairs.”

There were some troubling findings as well. The drug causes flu-like side effects and produces reactions, such as welts and swelling, where it is injected. Moreover, one person who got Betaseron committed suicide, and three more attempted to kill themselves. Experts say there is no way to assess whether Betaseron played a role; MS often makes patients depressed, yet there were no suicide attempts in the control group.

The positives about Betaseron clearly outweighed the negatives in the eyes of the U.S. Food and Drug Administration, which approved Betaseron for multiple sclerosis in July. The approval, which Johnson and other experts believe was influenced heavily by the MRI test results, was unusually quick; FDA officials normally take up to three years to review new drug applications, but Betaseron was approved in just one year.

That was the good news. The bad news was that Berlex wasn’t ready.

The company Berlex contracted to manufacture Betaseron, Chiron Corp. in Emeryville, Calif., had been making the drug in tiny quantities, just enough for experimental use. Now there was a huge demand, and Chiron--which had planned to build new manufacturing facilities while the FDA took its time pondering Betaseron’s approval--couldn’t meet it.

Berlex was in a quandary.

Simply putting the drug out on the market and letting people scramble for it would do no good; Betaseron must be taken every other day, and patients needed to be assured a continuous supply. Nor, Latts says, did company officials want to put themselves in the position of picking people who might benefit the most from Betaseron; that seemed a little too much like playing God, and in any event there is not enough research to support such a determination.

So they settled on the lottery--a term the company dislikes, for it implies there are losers. The deadline for what Berlex has termed the “open registration” for Betaseron was Sept. 15.

Across America, nearly 67,000 people whose doctors believed they were good candidates for Betaseron registered with Berlex for the computerized drawing. And then the waiting began.

In Hesperia, a fast-growing town on the road to Las Vegas, where Joshua trees and fast-food restaurants dot the landscape, the High Desert MS Support Group was watching closely. The group meets every other week for comfort and laughter.

There is Clint, a retired peace officer and the only Republican of the clan, who takes endless grief for being a Rush Limbaugh devotee. There is Deborah, a former athlete, and Michele, the group’s founder. There is David, the “baby” of the group at age 25, who sometimes brings his mom to meetings. And Don, who arrived a year ago with a chip on his shoulder and now pointedly tells a visitor: “If you’re looking for a bunch of people wallowing in self-pity, you’ve come to the wrong place.”

And, of course, Sharon and Alison. They are the bookends, the lowest and highest lottery numbers in the group.

They have come to grips with this disparity quite neatly, in a way that spares their friendship any pain. Sharon, they have decided, is “the guinea pig.” All will be watching to see what this drug does for--or to--her.

After just three weeks of therapy, it is too soon to tell. While the friends are optimistic, they are realists as well. Years have passed with no new treatments for MS. During that time, they have watched themselves and the people they love deteriorate. In the back of their minds is a nagging fear that Betaseron might not live up to its promise. In the way that they have of finishing one another’s sentences, they offer this summation:

“We all started out . . . “ Sharon says, until Alison interjects: “A little more hopeful than we are right now.”

Making Progress

A new genetically-engineered drug, Betaseron, has been shown to slow the crippling effects of multiple sclerosis, a progressive disorder in which the immune system mistakenly attacks the body. Betaseron, expensive and in limited supply, is being distributed through a lottery system.

The disease

Multiple sclerosis targets the central nervous system--the brain and spinal cord. The disease destroys the myelin sheath, the protective cover that surrounds the nerve fibers that send messages to the body. Without myelin, nerve fibers cannot send messages properly. Thus the brain of an MS patient cannot tell the body what to do, leaving MS patients with a host of debilitating symptoms, among them blindness, paralysis, memory loss, bladder dysfunction and slurred speech.

Betaseron

Betaseron apparently slows the destruction of the myelin sheath, although scientists are not sure why. Some think myelin is destroyed when the body makes an excess of gamma interferon, a naturally occurring protein that may prompt the immune system to attack the myelin sheath.

Another kind of interferon--beta interferon--stifles gamma interferon. Betaseron, a genetically engineered form of beta interferon, is thought to suppress the immune system attacks. The drug does not reverse damage already done by the disease but appears to keep MS patients from getting worse.