Allos Therapeutics: Promising Data

Allos Therapeutics, Inc. (NASDAQ: ALTH) announced safety results from its Phase I/II trial of Pralatrexate (PDX) in patients with non-Hodgkin's lymphoma and Hodgkin's disease, and from its Phase II study of efaproxyn in patients with unresectable non-small cell lung cancer receiving sequential chemoradiotherapy (S-CRT).

Results of the PDX sudy indicate a higher incidence of stomatitis was observed in patients with elevations in pre-treatment homocysteine (Hcy) and methylmalonic acid (MMA). Little to no increase in stomatitis occurred in patients with Hcy and MMA less than 10 mM and 200 nM respectively. Patients with elevated Hcy and MMA who developed stomatitis with PDX did not develop advanced grade stomatitis after normalization of their Hcy and MMA with folic acid and vitamin B12 supplementation. Subsequent to this finding, all enrolled patients have received pre-treatment with vitamin B12 and folic acid, and normalization of Hcy and MMA levels has mitigated the incidence of stomatitis.

In July 2006, the FDA awarded orphan drug designation to PDX for the treatment of patients with T-cell lymphoma. PDX is a novel, small molecule chemotherapeutic agent that inhibits dihdrofolate reductase (DHRF), a folic acid dependent enzyme involved in the building of DNA and other processes. PDX was rationally designed for improved transport into tumor cells via the reduced folate carrier (RFC-1), and greater intracellular drug retention. These biochemical features, together with preclinical data in a variety of tumors, suggest that PDX has an enhanced potency and improved toxicity profile relative to methotrexate and other related DHFR inhibitors.

The efaproxyn study compared the safety and efficacy of efyaproxyn when administered with S-CRT in patients with unresectable NSCLC compared to data from a Phase III, Radiation Therapy Oncology Group (RTOG) study. Results of a 5-year survival analysis indicated that patients in the efaproxyn study exhibited superior survival to patients with similar characteristics in the RTOG study. Median survival of patients treated in the efaproxyn study was 20.6 months as compared to a median survival of 13.3 months for matched cases in the S-CRT arm of the RTOG study and 16.9 months in the concurrent chemoradiotherapy (C-CRT) arm of the RTOG study. The Kaplan-Meier estimates of 5-year survival rates for matched cases were 19% in the efaproxyn study and 10% in both the S-CRT and C-CRT arms of the RTOG study.

Efaproxyn is the first synthetic small molecule designed to sensitize hypoxic or oxygen-deprived areas of tumors during radiation therapy by facilitating the release of oxygen from hemoglobin, and increasing the level of oxygen in tumors. The presence of oxygen in tumors is an essential element for the effectiveness of radiation therapy. By increasing tumor oxygenation, Allos believes that efaproxyn has the potential to enhance the efficacy of standard radiation therapy.