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Results of Phase 3 Trial of Efaproxiral Fail to Demonstrate Significant Improvement in Overall Survival in Breast Cancer Patients
"I would like to acknowledge the patients and investigators for their participation in the ENRICH study," said Paul L. Berns, President and Chief Executive Officer of Allos. "We continue to move forward with focus and determination in advancing the clinical development of PDX and RH1, and look forward to providing future updates on our clinical progress."
Results of the ENRICH study indicated that patients who received Efaproxyn plus WBRT did not experience a statistically significant improvement in survival compared to patients who received WBRT alone, according to a stratified log rank analysis of overall survival (8.5 months vs. 7.5 months; hazard ratio 0.87, p-value = 0.23). All secondary efficacy endpoints also failed to achieve statistical significance. The study safety results demonstrated that Efaproxyn was generally well tolerated. The most common Grade 3-4 adverse events that occurred more often in the Efaproxyn arm included headache, hypoxia and vomiting. Adverse events in the study appeared to be similar to those observed in previous clinical studies with Efaproxyn.
"Although we are disappointed with the results of the ENRICH study, we are excited about the potential of our product pipeline," said Dr. Pablo J. Cagnoni, Allos' Chief Medical Officer. "We expect to provide the next update on our PDX PROPEL study later this year following completion of a pre- specified interim analysis of response data after 35 patients have completed at least one cycle of treatment with PDX."
PDX (pralatrexate) is a novel, small molecule chemotherapeutic agent that inhibits dihydrofolate reductase, or DHFR, a folic acid (folate)-dependent enzyme involved in the building of nucleic acid, or DNA, and other processes. PDX was rationally designed for efficient transport into tumor cells via the reduced folate carrier, or RFC-1, and effective intracellular drug retention. The Company believes these biochemical features, together with preclinical and clinical data in a variety of tumors, suggest that PDX may have a favorable potency and toxicity profile relative to methotrexate and certain other DHFR inhibitors. The Company believes PDX has the potential to be delivered as a single agent or in combination therapy regimens.
PROPEL is an international, multi-center, open-label, single-arm pivotal Phase 2 clinical trial of PDX in patients with relapsed or refractory PTCL. The trial will seek to enroll 100 evaluable patients at approximately 35 centers across the United States, Canada and Europe. The primary endpoint of the study is objective response rate (complete and partial response). Secondary endpoints include duration of response, progression-free survival and overall survival. In August 2006, the Company reached agreement with the FDA under the Special Protocol Assessment, or SPA, process on the design of this pivotal Phase 2 trial. According to the PROPEL trial protocol, the Company will conduct an interim analysis of efficacy data from the PROPEL trial after 35 patients have completed at least one cycle of treatment with PDX, and must observe at least four responses (complete or partial) out of the first 35 patients in order to continue the trial. The Company currently expects to conduct the 35 patient efficacy analysis in the second half of 2007 and complete patient enrollment in the trial by the third quarter of 2008, although the actual timing of the interim analysis or completion of enrollment may vary based on a number of factors, including site initiation and patient enrollment rates.
About Peripheral T-cell Lymphoma
Peripheral T-cell lymphomas, or PTCLs, are a biologically diverse group of blood cancers that account for approximately 10% to 15% of all cases of non- Hodgkin's lymphoma (NHL), or about 6,700 patients. The average five year survival rate for PTCL patients is approximately 25%. There are currently no pharmaceutical agents approved for the treatment of either first-line or relapsed or refractory PTCLs.
Efaproxyn (efaproxiral) is a synthetic small molecule designed to sensitize hypoxic, or oxygen-deprived, areas of tumors during radiation therapy by facilitating the release of oxygen from hemoglobin, the oxygen-carrying protein contained within red blood cells, and increasing the level of oxygen in tumors. The presence of oxygen in tumors is an essential element for the effectiveness of radiation therapy.
ENRICH was a randomized, open-label, multi-center Phase 3 study designed to evaluate the safety and efficacy of WBRT with supplemental oxygen with or without Efaproxyn in women with brain metastases originating from breast cancer. The trial enrolled 368 patients at 78 centers in the United States, Canada, Europe and South America. The primary endpoint of the study was overall survival. Secondary endpoints included response rate in the brain at three months, Karnofsky Performance Status, and neurologic signs and symptoms assessment.
Source: Allos Therapeutics