New analyses of data from Allos Therapeutics’ pivotal PROPEL trial of FOLOTYN reported

Allos Therapeutics, Inc. (Nasdaq: ALTH) today reported new analyses of data from the Company’s pivotal PROPEL trial of FOLOTYN™ (pralatrexate injection) in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). In addition, the Company reported preliminary results from its Phase 1/2 study of FOLOTYN in combination with gemcitabine in patients with relapsed or refractory lymphoproliferative malignancies. These data were presented during a poster session at the 51st Annual Meeting of the American Society of Hematology (ASH) in New Orleans, LA.

In September 2009, the U.S. Food and Drug Administration (FDA) granted accelerated approval for FOLOTYN for use as a single agent for the treatment of patients with relapsed or refractory (PTCL). FOLOTYN is the first and only drug approved by the FDA for this indication and represents a new treatment option for patients with relapsed or refractory PTCL. This indication is based on overall response rate. Clinical benefit such as improvement in progression free survival or overall survival has not been demonstrated. FOLOTYN has been available to patients in the U.S. since October 2009.

The PROPEL posters included an update of overall response rate for FOLOTYN as evaluated by independent central review using International Workshop Criteria (IWC). Treatment with FOLOTYN achieved an overall response rate of 29% (32 of 109 evaluable patients). Sixty-three percent (63%) of patients responded within the first cycle of therapy. Responses were durable with a median duration of response of 10.1 months. Median overall survival was 14.5 months.

“FOLOTYN is an important new therapy for patients with relapsed or refractory PTCL and for physicians who treat patients afflicted with this very aggressive cancer,” said Owen A. O'Connor, M.D., Ph.D., principal investigator in the PROPEL study of FOLOTYN; deputy director for Clinical Research and Cancer Treatment, NYU Cancer Institute; chief, Division of Hematologic Malignancies and Medical Oncology; professor of Medicine and Pharmacology at the NYU Langone Medical Center. “We continue to be encouraged by the observed responses in relapsed or refractory patients, including those whose cancer never responded to a wide range of prior therapies, including stem cell transplant therapy.”

Below is a summary of conclusions and key findings from the poster presentations. To view the complete posters, go to the Company’s web site and look under the “Presentations” tab of the “Investor Relations” section of the website (www.allos.com).

PROPEL Poster Presentations

Abstract #1678 Pralatrexate Induces Responses in Patients with Highly Refractory Peripheral T-Cell Lymphoma (PTCL)

A poster presentation by Dr. Kerry Savage, of the British Columbia Cancer Agency, Vancouver, BC, Canada, characterized the response to FOLOTYN among patients with peripheral T-cell lymphoma in the PROPEL study who were considered to have refractory disease, defined as no evidence of response to their most recent treatment or to any prior therapies. Patients enrolled in PROPEL were a heavily pretreated population who had a median of 3 prior systemic therapies, with the most common being CHOP-based chemotherapy and other multi-agent chemotherapy regimens. Eighteen patients (17%) received autologous stem cell transplant prior to inclusion in the study. The results of this analysis showed FOLOTYN produced durable responses in patients with relapsed or refractory PTCL who had no response to prior therapies, including the subpopulation of patients who had no response to their most recent therapy as well as patients who were refractory to all prior therapies.

• Of the 109 evaluable patients, 69 patients (63%) had no evidence of response to the most recent prior therapy.
  • According to central review, these patients achieved a 25% (17/69) overall response rate, with a duration of response ranging from 41 to 673 days. A 36% (25/69) overall response rate was observed in these patients according to investigator review.
• Among the 69 patients, 26 patients (24%) had no evidence of response to any prior therapy before initiating FOLOTYN.
  • According to central review, 5 (19%) of these patients responded to FOLOTYN with a duration ranging from 54 to 306 days. Seven of these patients (27%) responded according to investigator review.
• Additionally, 76 patients (68%) received full dose FOLOTYN therapy at 30 mg/m² despite heavy pretreatment. Forty-six patients (67%) who had no response to their most recent therapy received full-dose therapy at 30 mg/m².

Abstract #1675 Safety and Management of Pralatrexate Treatment in Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)

A poster presentation by Dr. Lauren Pinter-Brown, of the University of California at Los Angeles, CA, assessed the safety of the patients included in PROPEL over three clinically important parameters: duration of FOLOTYN treatment, early- and late-onset FOLOTYN toxicities, and the impact of FOLOTYN dose modification on toxicities. Overall, 115 patients were enrolled in the study. The baseline and safety population included 111 patients who received ≥1 dose of FOLOTYN and excluded 4 patients not receiving therapy. In the PROPEL trial overall safety population, the safety results indicate that FOLOTYN was found to be well tolerated in patients with PTCL.

• The 4 most commonly observed adverse events were mucosal inflammation, nausea, thrombocytopenia and fatigue.
• Despite a median of 3 prior systemic therapies with potentially associated organ toxicities, the majority of patients tolerated the full dose FOLOTYN of 30 mg/m².
• The protocol-specified dose modification schema effectively reduced the occurrence of mucosal inflammation. Adherence to the FOLOTYN dose-modification guidelines permitted continued FOLOTYN therapy.
• The most common Grade 3-4 AEs for patients who initiated cycle 3 were observed at similar or lower rates compared to those observed in cycles 1-2. These data suggest that there is no cumulative-dose toxicity with FOLOTYN, which permits continued therapy for patients who derive benefit from FOLOTYN.

Abstract #1681 Correlation Between Baseline Methylmalonic Acid Status and Mucositis Severity in the PROPEL Study: Implications for Vitamin Prophylaxis

A poster presentation by Dr. Barbara Pro, of the University of Texas M.D. Anderson Cancer Center, Houston, TX, assessed baseline methylmalonic acid (MMA) status, homocysteine (HCY), and red blood cell (RBC) folate levels in patients enrolled in PROPEL. This baseline and safety population included 111 patients who received ≥1 dose of FOLOTYN and excluded 4 patients not receiving therapy. The analysis was conducted to determine if there was an association between these values and mucosal inflammation and thrombocytopenia observed in the study.

• The maximum mucosal inflammation grade experienced during FOLOTYN therapy (Grade 0 vs Grade 1-2 vs Grade 3-4) and the baseline MMA value had a statistically significant linear relationship>
• The analysis revealed no other significant relationship; and baseline HCY and RBC folate values were not predictive of the severity of mucositis or thrombocytopenia in this assessment.
• There was also a trend toward a relationship between increasing MMA and increasing severity of thrombocytopenia but did not meet statistical significance>
• Based on these results, vitamin supplementation of folic acid and vitamin B₁₂ is appropriate with FOLOTYN administration for relapsed or refractory PTCL.

FOLOTYN and Gemcitabine Study Poster Presentation

Abstract #1674 Pralatrexate and Gemcitabine in Patients with Relpased or Refractory Lymphoproliferative Malignancies: Phase 1 Results

A poster presentation by Dr. Steven M. Horwitz, of Memorial Sloan-Kettering Cancer Center, New York, NY, reviewed preliminary results from a Phase 1/2 study of FOLOTYN and gemcitabine in patients with B-cell lymphoma, PTCL and Hodgkin’s disease. The primary objective of the Phase 1 dose finding portion of this study was to evaluate the safety and preliminary efficacy of the combination of FOLOTYN and gemcitabine. The Phase 1 evaluation determined the maximum tolerated dose (MTD) of the combination of FOLOTYN and gemcitabine on sequential days and same day schedules. Patients were administered a combination of FOLOTYN and gemcitabine according to three regimens: on the same day every two weeks (q2w), on sequential days q2w, or on sequential days once weekly for three weeks of a four week cycle.

• These data demonstrated that treatment with FOLOTYN and gemcitabine is feasible, with acceptable toxicity, when administered on a q2w schedule.
• The dose administered of each drug is higher when given on the same day schedule as compared to treating on sequential day schedule.
• In this dose ranging study, preliminary results showed activity of the combination of FOLOTYN and gemcitabine in lymphoid malignancies with a 24% overall response rate in this heavily pretreated population.
• The Phase 2 expansion at the MTD will evaluate both sequential and same-day dosing of FOLOTYN in a q2w schedule.

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