SAN FRANCISCO In the wake of bad news about Xcytrin (motexafin gadolinium), which missed its co-primary endpoints in a Phase III trial for brain cancer metastasis, Pharmacyclics Inc. offered a closer look at the results that showed promise in those patients with lung cancer whose disease has spread to the brain.
That sector makes up 60 percent of the total market for the brain metastatic disease, the company noted. Based on the results, Sunnyvale, Calif.-based Pharmacyclics will be meeting with the FDA (while continuing to analyze the data), with an eye toward filing a new drug application as soon as possible, said Richard Miller, president and CEO.
Miller outlined for the first time the Phase III data in a slide show for attendees of the JPMorgan H&Q Healthcare Conference here. The trial was designed to compare the safety and efficacy of standard whole-brain radiation therapy to standard WBRT plus Xcytrin.
“The stratification is [according to] lung, breast or other other’ being a collection of a bunch of different tumors,” he said. “The prespecified data analysis plan calls for comparing survival and time to neurologic progression in all 401 patients.”
Xcytrin, one of a new class of drugs called texaphyrins, selectively accumulates in cancer cells and disrupts cellular metabolism by blocking the flow of energy in cancer cells, thus preventing them from repairing damage caused by the effects of radiation and chemotherapy.
At least for lung cancer patients, it seems to work.
“These curves come down in parallel over the first couple of months and then they separate, with an advantage in the Xcytrin-treated group,” Miller told a packed conference room, pointing to a slide of the Sunnyvale, Calif.-based company’s computer readout regarding 251 lung cancer patients in the study.
“The median time to neurologic progression in the control arm is 7.4 months, and the median time to neurologic progression in Xcytrin-treated patients has not been reached,” he said. “In other words, at 12 months, it hasn’t reached the 50 percent level.”
Miller also offered data for 214 recursive partitioning and amalgamation (RPA) Class II lung cancer patients, “the kind of lung cancer patient that walks in the door, 86 percent of lung cancer patients. Again the curves come down in parallel, and then they separate at about two to three months. There’s an advantage in the Xcytrin arm compared to the control arm the median time to neurologic progression in the control was 6.3 months [and in the Xcytrin arm] has not been reached at 12 months.”
In December, Pharmacyclics disclosed less than happy overall news from the study, which had co-primary efficacy endpoints of survival and time to neurologic progression. The data showed median survival to be 5.2 months for all patients treated with Xcytrin plus radiation therapy, compared to 4.9 months for control patients given only radiation. Median time to neurologic progression for all patients treated with Xcytrin plus radiation therapy was 9.5 months, compared to 8.3 months for those patients receiving radiation alone. (See BioWorld Today, Dec. 17, 2001.)
The company noted at the time that lung cancer patient results might turn out to be better, but Wall Street still brought punishment, knocking down Pharmacyclics’ stock (NASDAQ:PCYC) by 56.7 percent, to close at $9.39. Tuesday’s news provided a revival of sorts, with the shares ending the day at $10.33, up 67 cents, after trading as high as $10.94.
Xcytrin also is being studied for glioblastoma multiforme (GBM), a primary tumor of the brain. Results from a National Cancer Institute study, reported earlier at a scientific meeting, showed a median survival rate of 16.8 months for 28 patients. Miller also spoke to conference attendees about Pharmacyclics’ study, investigating safety and pharmacokinetics of Xcytrin in GBM patients.
“What you see here are very good results, with only a couple of deaths,” he said. “We have about 80 percent of patients alive past four months,” he said, adding that an abstract of the results has been submitted for the American Society of Clinical Oncology meeting, which will be held in May.
“We’ll be continuing to follow these patients on out,” Miller said, noting the follow-up has been shorter than that in the NCI study.
Meanwhile, in the next three to six months, the firm will complete the data analysis (probably in about one month), meet with the FDA and begin a Phase III trial in GBM (in the first half of this year). At the ASCO meeting, the company will be reporting on GBM, pancreatic cancer and the Phase III brain metastasis trial. Xcytrin also is being studied by the NCI in GBM, pediatric brain tumors, primary lung cancer and pancreatic carcinoma.
In the company’s Phase III data reported Tuesday, 75 patients had breast cancer and 75 had other types. Miller, swept from his conference presentation toward a breakout session in another room, noted to BioWorld Today that breast cancers and others are “very different” from lung cancer.
“Lung cancer patients have their tumor, they get brain [metastases], and they die, unfortunately,” he said. “Breast cancer gets brain [metastases], they go on hormones, they go on chemo, they go on this, they go on that. A lot of salvage therapies are available, a lot more treatment options. It muddies [the clinical picture].”
Miller said he has “no reason to think it wouldn’t work in breast cancer. In fact, most of the animal data we have is in breast cancer.” More definitive answers will come out of the analysis of the Phase III data, he added.