Washington Editor

Preliminary analysis of a pivotal Phase III trial of Allos Therapeutics Inc.'s RSR13 showed it failed to meet a statistical endpoint in patients with brain metastases, sending the stock tumbling. However, the 538-patient trial did demonstrate something else - a survival trend in breast cancer patients.

The median survival rate of breast cancer patients increased by 4.5 months to nine months, according to Allos, of Westminster, Colo.

"The metastatic breast cancer patients receiving RSR13 experienced almost a doubling in survival that was highly statistically significant," Michael Hart, Allos' president and CEO, said in a conference call Wednesday. "This is a remarkable observation and potentially a very promising development for these patients."

RSR14 (efaproxiral injection) is a synthetic small molecule that increases the release of oxygen from hemoglobin, which is important in treating hypoxia in connection with radiation treatments for cancerous tumors. RSR13 is designed to enhance radiation therapy by making it more effective. RSR13 has been issued fast-track and accelerated-approval status.

"The drug is being developed specifically to treat the tumor involvement in the brain. The hypothesis is that as physicians are treating the primary cancer that metastasized to the brain, if you can effectively treat the brain, the physician can use systemic therapy for a longer period of time, which leads to an increase in survival," Hart told BioWorld Today.

While the breast cancer outcome looks good, there was trouble with brain tumors, which explains the dive Allos' stock (NASDAQ:ALTH) took Wednesday. It closed at $1.90, down $1.50, or 44.1 percent.

"I think there's a bias in the biotechnology investor community that you only look at intent-to-treat groups and whether a trial reached statistical significance or not, and that's very unfortunate," Hart said. "It is important to note here that the reaction of the market probably has more to do with them trying to assess what the probability of approval is for RSR13 given this outcome. What we've tried to achieve here is to develop a drug for brain metastases independent of what the primary cancer was, and in oncology, that's unheard of."

Initiated in February 2000, the Phase III was a randomized, open-label study designed to compare the safety and efficacy of whole-brain radiation therapy (WBRT) combined with RSR13 to WBRT alone in patients with brain metastases. Of the 538 patients, 56 percent also had non-small-cell lung cancer (NSCLC), 21 percent had breast cancer and 23 percent had other cancers. The primary endpoint was overall survival. (Median survival in NSCLC patients increased three weeks.)

Patients receiving RSR13 plus WBRT experienced a 17.6 percent improvement in median survival compared to patients receiving WBRT alone (5.26 months vs. 4.47 months; p=0.17; n=538), Hart said. In the prospectively defined intent-to-treat group of patients with brain metastases from only breast cancer and NSCLC, patients receiving RSR13 had a 32.4 percent increase in median survival vs. control (5.91 months vs. 4.47 months; p=0.12; n=414).

Also, the company said there was a 48 percent increase in median survival among patients in the breast cancer and NSCLC intent-to-treat subgroup who were diagnosed with their original cancer before they were diagnosed with brain metastases and who were treated with RSR13 plus WBRT (6.60 months vs. 4.47 months; p=0.003; n=273.)

"When you peel the onion here, you see some very strong effects in breast cancer," Mark Monane, a senior biotechnology analyst with Needham & Company Inc. in New York, told BioWorld Today. "How much work the FDA will ask Allos to do to solidify that fact is the open question and it could range from the FDA saying this is a special exemption, it's a hard-to-treat population and the results are very dramatic to this is very impressive data and therefore you should use this as the basis for another trial."

Hart said his next step is to talk with the FDA and devise a plan for moving forward. "With such a larger heterogeneous population and data set, our opportunity now is to more specifically identify those patients who are most likely to benefit from adding RSR13 to standard radiation therapy and quite possibly certain chemotherapy," he told conference call listeners. "The results confirm our excitement about the potential survival benefit of RSR13 in patients with brain metastases, and it may represent a major breakthrough in patients with breast cancer."

Also, the company is considering its partnership options, Hart said.