Shares of the drug’s developer, Human Genome Sciences, were up more than 220 percent on Monday on the success of the trial. Almost all Wall Street analysts have been predicting the drug, known as Benlysta, would fail in the trial.
“For the one million people with lupus in the United States, this is nothing short of revolutionary,” said Dr. Daniel J. Wallace, a clinical professor of medicine at the University of California, Los Angeles, who was a consultant to Human Genome Sciences on the structure of the trial.
In the Human Genome Sciences study, a Phase 3 trial, 57.6 percent of patients on the higher dose of Benlysta and 51.7 percent of those on a lower dose had a meaningful improvement in their symptoms after one year. That compared with 43.6 percent of those taking a placebo.
There are caveats. The results have not yet been published or subjected to scrutiny by independent experts. The data suggests that the drug would help only 8 to 14 of every 100 patients treated. And the drug is likely to be far more expensive than the old generic immune suppressants and steroids now used to treat lupus.
Human Genome Sciences, based in Rockville, Md., is sharing development and marketing rights to the drug with GlaxoSmithKline. Results from a second Phase 3 trial are due in November. If that succeeds, the companies will apply for regulatory approval in the first half of next year.
Lupus is an autoimmune disease, in which the defense system against pathogens attacks the body’s own tissues. The disease, which primarily affects women of child-bearing age, can cause rashes, arthritis, mouth sores, kidney damage and other problems.
One recent study estimated that 322,000 Americans definitely or probably have systemic lupus erythematosus, the most common form of the disease and the one against which Benlysta was tested. The Lupus Foundation of America estimates that 1.5 million Americans have some form of lupus.
Because the disease’s symptoms wax and wane on their own and vary considerably from one patient to another, it has been hard to demonstrate the efficacy of drugs in clinical trials.
Among the companies that have had setbacks or outright failures in clinical trials are Roche and Biogen Idec with their drug Rituxan; La Jolla Pharmaceutical with Riquent; Bristol-Myers Squibb with Orencia; ZymoGenetics and Merck Serono with atacicept; Genelabs Technologies with Prestara; Teva Pharmaceutical Industries with edratide; and Aspreva Pharmaceuticals and Roche with CellCept.
Benlysta, which was previously called Lymphostat-B and is known generically as belimumab, also failed in its Phase 2, or midstage, trial.
But Human Genome Sciences, in consultation with the Food and Drug Administration, restricted the Phase 3 trials to a subset of patients who seemed to respond better to the drug in the earlier trial. It also changed the measurement of success and lengthened the trial to give the drug more time to work.
“We knew the drug was safe and biologically active,” H. Thomas Watkins, chief executive of the company, said in an interview. “The question was, ‘Can you prove in a very large trial what we’ve proven here?’ ”
The 865 patients in the trial, who were mainly in Asia, South America and Eastern Europe, received either Benlysta or a placebo in addition to the drugs they were already taking.
More patients on the drug had the required improvement in symptom severity. In addition, about 20 percent of patients taking Benlysta were able to reduce their use of the steroid prednisone by at least 25 percent, compared with about 12 percent of those on placebo.
Although the difference between the treated patients and those given the placebo in the trial might appear modest, Dr. Joan T. Merrill, a lupus expert at the Oklahoma Medical Research Foundation, said Benlysta’s safety and its ability to reduce steroid use would make it attractive to doctors. Steroids can cause severe weight gain, acne and the weakening of bones, among other side effects.
“I think it looks good,” Dr. Merrill said. “And we are in a field where we haven’t even had anything fair.”
Benlysta, which is given by infusion once every four weeks, inhibits the action of a protein in the body called B-lymphocyte stimulator, which helps B cells in the blood respond to infections. The company said high levels of the protein might spur the immune system to attach the body’s own tissues.
Human Genome, a pioneer in studying human genes, discovered the gene for the stimulator protein. If Benlysta gets to market, it will be the first drug from the company, and one of the first in the industry, to result from genomics.
In 2000, the company’s share price soared to over $100 on anticipation that understanding the human DNA blueprint — the human genome — would lead to a cornucopia of drugs. On Friday, it closed at $3.32 a share.
SOURCE: Andrew Pollock as reported on www.nytimes.com.