Guilford Pharmaceuticals Inc. completed a follow-up assessment of long-term survival based on an earlier Phase III trial of its Gliadel Wafer for patients with high-grade malignant glioma, and the study showed the risk of dying over three to four years after wafer implantation was reduced by 27 percent.
The follow-up study was completed after Baltimore-based Guilford's supplemental new drug application seeking approval of the Gliadel Wafer as a first-line treatment for the brain cancer was rejected earlier this year by the FDA. (See BioWorld Today, March 21, 2002.)
"This is a significant achievement for our company," Craig Smith, chairman and CEO of Guilford, said in a conference call with analysts and media on Thursday.
The dime-sized wafers consist of polifeprosan 20 with carmustine and are implanted in the cavity left when a malignant brain tumor is surgically removed.
Smith said that to conduct the long-term analysis, Guilford got follow-up data from 239 patients out of 240 that were enrolled in the earlier Phase III trial. In August, 228 were known to have died, and of the 11 patients still alive, nine had received the Gliadel Wafer and two received placebo.
During the three to four years of follow-up, the hazard ratio for Gliadel Wafer-treated patients relative to placebo-treated patients was 0.73 (p=0.017, unstratified log-rank test), meaning a 27 percent reduction in the risk of dying during the trial.
"The FDA has indicated that data of this sort would be of interest and could form the basis of their reconsideration, although they have made no commitments," Smith said during the call. "We have provided the data to them, and we are going to be discussing it with them in a short period of time."
In March, the FDA issued a non-approvable letter in response to Guilford's sNDA for use in patients with newly diagnosed malignant glioma. Gliadel was approved in 1996 for use as an adjunct to surgery in patients with recurrent glioblastoma multiforme.
The primary endpoint in the Phase III trial was overall survival, and participating patients were adult men and women undergoing initial surgical resection of a high-grade malignant glioma. Gliadel Wafers or placebo wafers were implanted in the resection cavity and followed by radiation therapy.
In that trial, Guilford's analysis indicated that, relative to the placebo group, the wafer group had a hazard ratio of 0.71, or a 29 percent reduction in the risk of dying during the trial. The "p" value was 0.03 for that treatment effect, determined using the log rank test, stratified by the country in which the treatment was administered.
In 2001, U.S. sales of the wafer reached $20.4 million. (See BioWorld Today, March 21, 2002.)
Guilford's stock (NASDAQ:GLFD) rose 8 cents Thursday to close at $4.20.