There hasn't been a new drug approved to treat lupus in 40 years.

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There hasn't been a new drug approved to treat lupus in 40 years.

And when LymphoStat-B looked like a failure in a recent clinical

trial, people with the painful disease braced for another in a long

line of disappointments. But the FDA is urging companies to better

target patients who will benefit from their drugs. And Human Genome

Sciences Inc. is poised to revive LymphoStat-B, on the hunch it knows

which lupus sufferers it will help. Will that gamble add millions to

the drug's research price, and are investors willing to take that risk?

By Diedtra , Globe Staff | November 14, 2005

The safe thing for Human Genome Sciences would be to walk away from

LymphoStat-B.

When the Rockville, Md., company that focuses on protein and antibody

drugs reported last month that its lupus treatment failed to meet

clinical goals, investors bolted and the company's stock plunged 30

percent.

Yet despite the dwindling support from the investment community,

Human Genome Sciences is taking a calculated bet that LymphoStat-B

will actually work in a more narrowly targeted group of lupus

sufferers -- based on, of all things, the results of the failed phase

II trial.

The company appears ready to spend millions of dollars to do a much

larger phase III study of LymphoStat-B, only this time on a subset of

lupus patients who are more likely to respond to the treatment. Just

assembling the right group of a few thousand lupus patients for the

next round of testing will be a considerable undertaking.

As risky as it sounds, Human Genome Sciences is actually following a

course recently charted by federal drug regulators. The Food and Drug

Administration has been championing personalized medicine. And, in a

few closely watched cases, regulators approved drugs whose

manufacturers clearly defined which kind of patients were most likely

to benefit from the potential treatment, and then spent their time

testing whether the drug would actually work on just that subset of

people.

NitroMed Inc. won FDA approval for its drug, BiDil, doing just that.

The Lexington company tested the heart failure treatment in just

African-American patients, a group that had more marked benefits in

early trials. Within a large study containing other ethnic groups,

those benefits would not have been so obvious.

The FDA has also signaled to companies making cancer drugs that it is

comfortable having them use genetic tests to determine which are the

optimal patients to receive treatment. This could ultimately increase

the number of people who benefit while reducing side effects and

expensive treatments on patients unlikely to respond.

Moreover, the agency is eager to provide more options for the up to

500,000 Americans who suffer from systemic lupus erythematosus, a

form of the disease that can affect many different parts of the body.

Lupus is a painful autoimmune disease in which patients can suffer a

range of symptoms, including fatigue, fever, skin rash, swollen

joints and, in severe cases, kidney and central nervous system problems.

Proving a drug is responsible when there are changes in that wide a

range of symptoms is one of the reasons why there hasn't been a new

treatment approved for lupus in four decades. After a different

experimental lupus drug failed late in development, the FDA issued a

regulatory road map that it hoped would lead drug companies to

produce successful treatments.

The phase II trial of LymphoStat-B showed promising results on a

subset of lupus patients: those who are seropositive, or whose blood

tests show they are actively under attack by the disease. While the

overall trial results fell short, seropositive patients reported

reduced symptoms of systemic lupus erythematosus at 52 weeks of

treatment. The trial's goal for LymphoStat-B was reduced symptoms at

24 weeks.

So Human Genome Sciences will screen patients for the phase III trial

to confirm they are seropositive. But the company has not said what

tests it will use to ensure patients in the next trial have signs of

lupus in their blood.

LymphoStat-B works pretty well among lupus patients who are slightly

sicker, said Dr. Joan T. Merrill, a medical professor at the

University of Oklahoma Health Sciences Center and medical director

for the Lupus Foundation of America.

That offers Human Genome Sciences a good head start, maybe, but it

doesn't guarantee a sure finish.

''To really do the right kind of trial, it's going to be a lot more

expensive. And we're not sure whether investors are going to go for

these kinds of ideas, " Merrill said. ''It becomes an enormous problem

to get a rationally designed clinical trial that is also practical. "

The blood tests add a step and another expense, among the ways a

beefed-up trial could add millions to the price tag, no small

endeavor for the many small biotech firms developing therapies today.

The dilemma for the investment community is gauging how much weight

to give to the company's next approach, since Human Genome has

revealed few specifics about how it would proceed.

''What they've been keeping sort of secret is what do they mean by

seropositive, " said J. , a W. Baird & Co.

analyst.

Jerry Parrott, Human Genome's corporate communications vice

president, said the company's next opportunity to provide these

details will come at a scientific meeting in June.

''At this point, all we could say is that we've identified a patient

population that we would study, " Parrot said. ''We know what the

active dose is. And we can see the design of the trial. "

The shortcoming of the earlier trial was that it accepted virtually

any lupus patient walking into a rheumatologist's office, he said. A

patient is diagnosed with lupus -- and qualified for the trial -- by

meeting four of 11 criteria.

''We did not, however, specify that they had to be seropositives, "

Parrot said.

Once the company completes its data analysis, meets with its partner,

GlaxoKline Plc., and the FDA, Parrot expects it can begin to

enroll patients in the phase III trial. That could be as early as

mid-2006 with Glaxo sharing the expenses.

Right now, lupus patients are treated with drugs borrowed from the

tool kits of doctors who handle diseases such as cancer.

For DeWilde, a Haverhill woman diagnosed with systemic lupus

while a high school sophomore, that meant deciding whether she wanted

relief from symptoms more than the opportunity to have a child later

in life. The powerful cancer treatment she was offered would rule out

having children. As it turned out, the doctors were wrong and

DeWilde, 24, is now six months pregnant.

The array of drugs she has used caused her hair to fall out and her

weight to fluctuate. She has been hospitalized for hypertension, high

blood pressure, and kidney infections.

She's currently in remission and, likely, would not test seropositive

for lupus. Still, she is thrilled Human Genome Sciences appears to be

moving forward on bringing the drug to market.

''It's just great they're moving ahead trying to find new

medications, trying to help people like us. "

Diedtra can be reached at dhenderson@.... 

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there_hasnt_been_a_new_drug_approved_to_treat_lupus_in_40_years/