New Analysis from FOLOTYN® PROPEL Trial Demonstrates Activity in Relapsed or Refractory Transformed Mycosis Fungoides

Allos Therapeutics, Inc. (NASDAQ:ALTH) today reported new analysis of data from the Company's pivotal PROPEL trial of FOLOTYN® (pralatrexate injection) in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) at the 52nd American Society of Hematology (ASH) Annual Meeting in Orlando, Florida. The objective of this retrospective subgroup analysis was to assess the activity and safety of single-agent FOLOTYN in patients enrolled in PROPEL who were diagnosed with histologically confirmed relapsed or refractory transformed mycosis fungoides (tMF), which is an aggressive and difficult to treat T-cell lymphoma.

"The activity observed in this analysis is extremely encouraging for patients with relapsed or refractory transformed mycosis fungoides, which is a difficult to treat and an aggressive form of T-cell lymphoma often associated with poor prognosis," said Francine Foss, M.D., professor of medicine (hematology) and of dermatology, Yale School of Medicine.

This analysis was based on assessment using International Workshop Criteria (IWC) by an independent central review as well as local investigator review. Of the 12 patients included in this analysis, objective responses were observed in three patients (25%) based on independent central review and in seven patients (58%) based on local investigator review. The median duration of response was 2.2 months based on independent central review and 4.4 months based on local investigator review. Prior to enrollment, patients with tMF received a median of 3 systemic therapies – eight patients (67%) had received prior treatment with a CHOP-based regimen (cyclophosphamide/doxorubicin/vincristine/prednisone).

The most common Grade 3-4 adverse events were mucositis (8%), fatigue (8%), and nausea (8%). The most common Grade 2 adverse events were mucositis (33%), fatigue (17%), nausea (8%), and pyrexia (8%). No patients discontinued therapy due to an adverse event.

“This analysis of the data from PROPEL provides important information about the clinical activity of FOLOTYN in patients with relapsed or refractory transformed mycosis fungoides. Results of this subgroup analysis demonstrated the activity and safety of single-agent FOLOTYN and its utility in patients with relapsed or refractory transformed mycosis fungoides,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics.

FOLOTYN is the first and only drug approved by the FDA for the treatment of 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.

About PROPEL

PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma), an open-label, single-arm, multicenter, international Phase 2 clinical trial, enrolled 115 patients with relapsed or refractory PTCL, 109 of whom were considered evaluable for efficacy according to the trial protocol. Patients were considered evaluable if they received at least one dose of FOLOTYN, their diagnosis of PTCL was confirmed by independent pathology review, and they had relapsed or refractory disease after at least one prior treatment. Patients were treated with FOLOTYN at 30 mg/m2 once weekly by IV push over 3-5 minutes for 6 weeks in 7-week cycles until disease progression or unacceptable toxicity. In addition, patients received 1mg of vitamin B12 intramuscularly every 8-10 weeks and 1.0-1.25 mg of folic acid orally on a daily basis.

The primary efficacy endpoint was overall response rate (ORR) – defined as complete response (CR), unconfirmed complete responses (CRu), and partial response (PR) – as assessed by International Workshop Criteria (IWC). The key secondary efficacy endpoint was duration of response. Response assessments were scheduled at the end of cycle 1 and then every other cycle (every 14 weeks). Duration of response was measured from the first day of documented response to disease progression or death. Response and disease progression were evaluated by independent central review using the IWC.

About Peripheral T-Cell Lymphoma

T-cell lymphomas comprise a biologically diverse group of blood cancers that account for approximately 10% to 15% of all cases of non-Hodgkin lymphoma (NHL) in the United States.1-3 The American Cancer Society estimated that approximately 66,000 new cases of NHL were expected to be diagnosed in the U.S. in 2010. The Company estimates the current annual incidence of PTCL in the U.S. to be approximately 5,900 patients. The outcome of patients with PTCL is poor and the majority of patients ultimately have refractory disease to a variety of agents, including multi-agent chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP-like regimens. The 5-year overall survival rate in these patients is 25% to 40%, depending on sub-type.4-5

About Transformed Mycosis Fungoides

Mycosis fungoides (MF) is a type of cutaneous T-cell lymphoma (CTCL)6 that first appears as a red, scaly rash. Generally, CTCLs are slow-growing and less aggressive than other T-cell lymphomas. However, in 11 to 23 percent of cases, MF transforms into a more difficult to treat disease referred to as transformed mycosis fungoides (tMF)7. tMF is an aggressive disease which is generally associated with poor prognosis for patients; the median overall survival in patients with tMF is 12-22 months from the time of diagnosis8. Based on the aggressive nature of tMF, these patients were eligible for the PROPEL study.

About FOLOTYN

FOLOTYN, a folate analogue metabolic inhibitor, was discovered by Sloan-Kettering Institute for Cancer Research, SRI International and Southern Research Institute and developed by Allos Therapeutics. 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). 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.

About Allos Therapeutics

Allos Therapeutics, Inc. (Nasdaq: ALTH) is a biopharmaceutical company committed to the development and commercialization of innovative anti-cancer therapeutics. Allos is currently focused on the development and commercialization of FOLOTYN® (pralatrexate injection), a folate analogue metabolic inhibitor. FOLOTYN is the first and only drug approved in the U.S. for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. Allos is also developing FOLOTYN in other hematologic malignancies and solid tumors. Allos retains exclusive worldwide rights to FOLOTYN for all indications. Allos is headquartered in Westminster, CO. For additional information, please visit www.allos.com.

IMPORTANT SAFETY INFORMATION

Warnings and Precautions

FOLOTYN may suppress bone marrow function, manifested by thrombocytopenia, neutropenia, and anemia. Monitor blood counts and omit or modify dose for hematologic toxicities.

Mucositis may occur. If ≥Grade 2 mucositis is observed, omit or modify dose. Patients should be instructed to take folic acid and receive vitamin B12 to potentially reduce treatment-related hematological toxicity and mucositis.

FOLOTYN can cause fetal harm. Women should avoid becoming pregnant while being treated with FOLOTYN and pregnant women should be informed of the potential harm to the fetus.

Use caution and monitor patients when administering FOLOTYN to patients with moderate to severe renal function impairment.

Elevated liver function test abnormalities may occur and require monitoring. If liver function test abnormalities are ≥Grade 3, omit or modify dose.

Dermatologic reactions may occur. Patients with dermatologic reactions should be monitored closely, and if skin reactions are severe, FOLOTYN should be withheld or discontinued.

Adverse Reactions

The most common adverse reactions were mucositis (70%), thrombocytopenia (41%), nausea (40%), and fatigue (36%). The most common serious adverse events are pyrexia, mucositis, sepsis, febrile neutropenia, dehydration, dyspnea, and thrombocytopenia.

Use in Specific Patient Population

Nursing mothers should be advised to discontinue nursing or the drug, taking into consideration the importance of the drug to the mother.

Drug Interactions

Co-administration of drugs subject to renal clearance (e.g., probenecid, NSAIDs, and trimethoprim/sulfamethoxazole) may result in delayed renal clearance.

Please see FOLOTYN Full Prescribing Information at www.FOLOTYN.com.

Note: The Allos logo and FOLOTYN name are trademarks of Allos Therapeutics, Inc.

References:

Savage KJ. Peripheral T-cell Lymphomas. Blood Rev. 2007; 21:201-216.
Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update [review]. Lancet Oncol. 2004;5(6):341-353.
O'Leary HM, Savage KJ. Novel therapies in peripheral T-cell lymphomas [review]. Curr Oncol Rep. 2008;134(5):202-207.
Savage KJ, Chhanabhai M, Gascoyne RD, et al. Characterization of peripheral T-cell lymphomas in a single North American institution by the WHO classification. Ann Oncol 2004;15(10):1467-75.
The Non-Hodgkin's Lymphoma Classification Project. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. Blood. 1997;89(11):3909-3908.
Cutaneous T-Cell Lymphoma Fact Sheet. Lymphoma Research Foundation. http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=6300151. Accessed: November 10, 2010.
Pralatrexate Is An Effective Treatment for Heavily Pretreated Patients with Relapsed/Refractory Transformed Mycosis Fungoides (tMF). Abstract. Accessed: November 18, 2010.
Arulogun, SO et al. Long-term outcomes of patients with advanced-stage cutaneous T-cell lymphoma and large cell transformation. Blood. 2008; 112:3082-7.