By Randall Osborne
Six months after reporting mixed preliminary findings from a Phase III trial of its lupus drug, Genelabs Technologies Inc. has released the study's final data.
Although the trial's outcome did not change, the company is more encouraged and is using some of the results to fine-tune its ongoing, second Phase III trial of the drug.
When Genelabs, of Redwood City, Calif., released its preliminary data in April, the company's stock dropped 27 percent. (See BioWorld Today, April 28, 1997, p. 1.)
But since the early peek at the first trial's data, much is different, said Irene Chow, president and CEO of Genelabs.
"At that time, we had not done all of our analysis," Chow said. "More important, we had not sat down with the FDA," which now has reviewed with the company its full report on the study.
"They said we could use it," Chow said.
The double-blind, randomized, placebo-controlled study of GL701, Genelabs' dehydroepiandrosterone (DHEA)-based drug, tested 191 women at 18 sites. DHEA is a naturally occurring hormone produced by the adrenal glands, and lupus patients usually show abnormally low levels.
All the patients in the trial were afflicted with mild to moderate cases of systemic lupus erythematosus, a chronic autoimmune disease that can be fatal. They received one of three daily treatments over the course of seven to nine months: 100 mg of GL701, 200 mg of the drug;,or a placebo.
The patients also were taking 10 to 30 mg daily of prednisone, a synthetic steroid. Because prednisone, commonly used as treatment for lupus, has many undesirable side effects, the study's endpoint was reduction of prednisone dose to 7.5 mg daily or less for at least two consecutive months.
The 7.5 mg steroid level is about the same as that which occurs normally.
Of the 137 patients in the study with "active" disease, 51 percent who received 200 mg of GL701 achieved the primary endpoint, compared with 29 percent of the placebo group — a statistically significant number.
Active disease is determined by using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), on which scores range from 0 to 22. Each patient was rated at enrollment, and those with scores of greater than 2 — which amounted to 72 percent of patients — were declared to have active lupus.
Whenever the patient's SLEDAI score did not increase from the previous visit, prednisone doses were reduced.
Patients With Inactive Lupus Affected Results
It was those patients below the score of 2 on the SLEDAI scale who, when added to the mix, diluted the statistical significance of the findings. But most of those patients, Chow said, have lupus only in their blood, with no outward symptoms.
"The data remained the same," Chow said. The completed trial shows that GL701 "is really only effective in terms of disease activity," which is where it counts, she said.
Knowledge gained from this trial will help with the ongoing Phase III study, begun in March 1996, Chow said. That trial, planned with 300 patients at 24 sites, has completed enrollment six months early. Its endpoint is modification of the disease, including clinical symptoms.
"We'll add more patients [to the second Phase III trial] whose SLEDAI score is greater than 2," Chow said, although she was not certain how many. "By the end of the third quarter next year, we should have no problem getting enough to detect statistical significance."
Talks with the FDA have gone well, Chow said. Ordinarily, two pivotal trials are required for each endpoint, but the agency has allowed Genelabs to proceed with one Phase III trial per endpoint. If results from the second Phase III trial are positive, they may be used with the data from the first, as part of the filing of a new drug application.
"Hopefully, [the two trials] are correlated," Chow said. "They should be."
The FDA promised to "work with" Genelabs to make data available as early as possible from the second Phase III trial, she said. "Can we achieve that? We don't know," Chow said. "The important thing is to get this onto the market and help the patients. We're on schedule."
Data from the first Phase III trial were presented at the meeting of the American College of Rheumatology in Washington, D.C.
Genelabs' stock (NASDAQ:GNLB) closed Wednesday at $3.812, down $0.125. *