Nov. 15, 2010 (Atlanta) -- People with lupus given the first in a new class of experimental drugs that target the disease process did better than patients given standard treatment, according to one-year results of a large clinical trial.
Longer follow-up of the patients suggests that over time, the difference in response rates between people given the new drug, Benlysta, plus standard therapy and patients given standard therapy alone becomes less pronounced, suggests research reported here at the annual meeting of the American College of Rheumatology (ACR).
Still, the study investigators and makers of the drug hope the results of this and other research will lead to FDA approval of the drug for use in some adults with active lupus who are receiving standard therapy.
An FDA advisory panel of outside experts will meet Tuesday to discuss and vote on whether the benefits of Benlysta outweigh the drug's risks. The FDA is not required to follow the advice of its advisory committees, but typically does.
If approved, Benlysta would become the first new drug for lupus in five decades.
FDA Reviews Express Concern
In documents released on the FDA web site last week in advance of the advisory panel meeting, FDA reviewers expressed concern about whether the "somewhat marginal" effectiveness of the drug outweighs the potential increased risk of death, infection, and psychiatric effects, including suicide, associated with its use.
Researcher Joan T. Merrill, MD, medical director of the Lupus Foundation of America, tells WebMD that overall, Benlysta "has a very nice safety profile" and that its benefits clearly outweigh its risks.
In two studies being considered by the FDA panel, people given Benlysta did better on two different measures than people given standard treatment alone, she says.
About 1.5 million Americans have lupus, a complex disease in which the immune system inappropriately attacks a person’s own tissues, wreaking havoc on the joints, skin, and other organs. Benlysta dampens the abnormal immune signals, calming down the immune system.
Benlysta Reduces Lupus Flare-ups at 1 Year
The study presented at ACR involved more than 800 patients on standard therapy, including steroids, for lupus. One third were also given a high dose of Benlysta, one-third a low dose, and one-third got placebo.
One-year response rates -- the study's primary goal -- were 43% in the high-dose Benlysta group, compared with just 34% of those on standard treatment.
By 76 weeks, the gap had narrowed: 39% of patients on high-dose Benlysta responded vs. 32% of those on placebo, a difference that could have been due to chance.
Similarly, at one year, patients taking Benlysta had fewer disease flare-ups and fewer severe flare-ups. And they reported less fatigue. By 76 weeks, the figures between the high-dose Benlysta and standard treatment groups were similar, says researcher Richard Furie, MD, a rheumatologist from North Shore-Long Island Jewish Health System. He has received funding from for Human Genome Sciences Inc. and GlaxoSmithKline, which are developing the drug and funded the studies.
And although Benlysta was associated with a reduction in steroid use at one year, that advantage too seemed to wane at 76 weeks. One of the most important goals of treatment is to get patients off steroids, which cause many undesirable side effects, including bloating, weight gain, acne, and high blood pressure.
Merrill says, "It could be [patients] did very, very well on standard therapy. We don’t know how the drug would do against nothing. In any lupus treatment, when you get close to a 40% [response rate], you are doing very, very well.
"If [standard] treatment is in the 30%-40% range, you have a problem analyzing your data. ... The problem is the standard treatment group, not the drug," she says.
Benlysta for Lupus: Side Effect Profile
Nearly all patients in both the studies being considered by the FDA panel -- whether they were given Benlysta or placebo -- experienced some side effect, including headache, muscle pain, upper respiratory tract infection, urinary tract infection, and influenza.
However, "treatment with [Benlysta] appeared to be associated with an increase in death, serious adverse events, infections and serious infections, and neurologic and psychiatric adverse events/serious adverse events, including three suicides in Benlysta-treated patients," the FDA reviewers write.
Says Merrill, "In some of the areas where this drug was tested, those infections are not as uncommon as in the U.S. I looked at these data, and I thought they were low, terrific. ... The infections were well within the bounds of any other biologic [agent] and look better than most."
Although the number of deaths was numerically higher in the Benlysta group in the new study -- 11 vs. 3 in the standard treatment group -- the difference could have been due to chance.
"It is what you expect. It is less than 1% of patients," Merrill says. "You wouldn’t see an effect on mortality in one year."
Harvard Medical School's Elena Massarotti, MD, who moderated the session at which the most recent data were presented, tells WebMD that Benlysta may have a role in the treatment of lupus patients.
The drug met its primary goal in two major studies and seems to have a good safety profile, she says.
The FDA is expected to issue a final decision by Dec. 9.
Epratuzumab Also Shows Promise for Lupus
Also at the ACR meeting, researchers reported on the investigational drug epratuzumab, which is in earlier-stage testing.
In a study of 227 people with moderate to severe lupus, epratuzumab was associated with a meaningful reduction in disease activity compared with placebo, says study leader Daniel Wallace, MD, of the David Geffen School of Medicine at UCLA.
In the 12-week study, the rate of serious side effects, including infections, appeared to be similar among both groups, he says.
Reduced disease activity was seen in as little as eight weeks, according to findings of the study, which tested a variety of doses of epratuzumab.
Epratuzumab is a monoclonal antibody that targets the CD22 molecule, which is thought to be a regulator of B cells that contribute to lupus by producing antibodies against the body's own tissues. This, in turn, causes the immune system to turn on itself, resulting in inflammation and tissue damage.
Commenting on the findings, Merrill says, "This was a very important study" that tells researchers the best dose to use as they move into large-scale testing required for FDA approval.
Future research, she adds, will include finding out whether the treatment can help spare the use of steroids in patients.
This study was presented at a medical conference. The findings should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.