About Cutaneous Lymphoma

Updated Results from FOLOTYN® Phase 1 Dose Finding Study Demonstrates Activity in Relapsed or Refractory Cutaneous T-Cell Lymphoma

Sun, 12/05/2010

Relapsed or Refractory Cutaneous T-Cell Lymphoma  
– Data presented at the 52nd American Society of Hematology Annual Meeting –
ORLANDO, Fla., & WESTMINSTER, Colo., December 5, 2010 – Allos Therapeutics, Inc. (NASDAQ: ALTH) today reported updated results from the Company’s Phase 1 dose-finding study of FOLOTYN® (pralatrexate injection) which supports the selection of 15 mg/m2 weekly for three weeks out of a four-week cycle as the optimal starting dose and schedule for further evaluation in patients with relapsed or refractory cutaneous T-cell lymphoma (CTCL).  Data were presented at the 52nd American Society of Hematology (ASH) Annual Meeting in Orlando, Florida.  
“We are continually seeking active and safe systemic therapies to improve the outcomes for our patients with CTCL,” said Steven Horwitz, M.D., assistant attending medical oncologist, Memorial Sloan-Kettering Cancer Center, who is serving as the study chair.  “The overall activity in this trial, including the high response rates, durability of response, and favorable safety profile is quite promising.  These results suggest that pralatrexate at this dose and schedule may be another important option for treating CTCL.”   
CTCL is a group of T-cell non-Hodgkin lymphomas.  In its early stages, CTCL primarily affects the skin, causing patches, plaques, and tumors, as well as redness and itching; however, as it progresses, CTCL can spread to the blood, lymph nodes, and internal organs.  For some patients, their disease will progress despite treatment with topical and skin directed therapies and will require systemic treatments, including chemotherapies.1-2  Even when CTCL is found in an early stage, it can be difficult to treat and usually returns after initial treatment.2   
This open-label, multi-center, dose-finding Phase 1 study enrolled 54 patients with relapsed or refractory CTCL who received at least one prior systemic therapy.  The first phase of the study employed a dose de-escalating strategy to determine an active, well-tolerated dose and schedule of FOLOTYN in this population.  Once the optimal starting dose and schedule was determined to be 15 mg/m2 weekly for three weeks out of a four-week cycle, this cohort was expanded to include a total of 29 patients.  The Company had previously announced interim results from this study.  
At ASH 2010, data were presented on the 29 patients treated at the optimal starting dose and schedule.  Results showed:

 Overall response rate – the percentage of patients whose cancer or tumor was reduced or disappeared after treatment with FOLOTYN – was 45 percent (13 out of 29 patients).

 At the optimal dose, responses were durable – with a Kaplan-Meier estimate for duration of response of 73 percent at six months.   

 Median progression-free survival had not been reached at the time of this analysis.  At the optimal dose, progression-free survival ranged from 1-429 days.    

Of the total 54 patients enrolled in the trial (which includes patients who received lower than the optimal dose), objective responses were observed in 22 patients (41%), including three complete responses (CR) and 19 partial responses.  In total, 41 of the 54 patients were treated at the optimal dose of FOLOTYN or higher; of these 41 patients, responses were observed in 21 patients (51%).  Responses to FOLOTYN were observed in patients whose disease failed to respond to key prior systemic therapies, including 46 percent of patients whose disease failed to respond to oral bexarotene, 46 percent whose disease failed to respond to methotrexate, 41 percent whose disease failed to respond to HDAC inhibitors, and 36 percent whose disease failed to respond to interferon.  Patients in the study were heavily pretreated, having received a median of 6.5 prior therapies (range 1-25) and 4.0 prior systemic therapies (range 1-11).
All 41 patients treated at the optimal dose or higher were evaluable for safety; of these patients, Grade 3-4 adverse events observed were mucositis (17%), thrombocytopenia (3%), and fatigue (3%); the most common Grade 1-2 adverse events observed were fatigue (34%), mucositis (31%), nausea (31%), epistaxis/nose bleeds (24%), edema (14%), and vomiting (14%).  There was no neutropenia reported in patients at the optimal dose or higher.  
“Allos is pleased with the results observed in this early study which demonstrated the activity of FOLOTYN in heavily pretreated patients with relapsed or refractory cutaneous T-cell lymphoma,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics.  “Based on these results, Allos intends to continue investigating the role of FOLOTYN as an option for patients with cutaneous T-cell lymphomas.”
About Cutaneous T-Cell Lymphoma
Cutaneous T-cell lymphoma, or CTCL, is comprised of indolent non-Hodgkin T-cell lymphomas which have their primary manifestations in the skin.  The most common CTCL subtypes are mycosis fungoides and Sézary syndrome.  According to the Lymphoma Research Foundation, CTCL accounts for approximately 2% to 3% of the estimated 66,000 new cases of non-Hodgkin's lymphoma diagnosed each year in the United States.  The estimated annual prevalence of CTCL in the United States is between 16,000 and 20,000 cases in the U.S.1
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.
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.  
Safe Harbor Statement This press release contains forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding the potential safety and efficacy of FOLOTYN for the treatment of patients with relapsed or refractory CTCL, the potential future development of FOLOTYN for the treatment of patients with relapsed or refractory CTCL; and other statements that are other than statements of historical facts. In some cases, you can identify forward-looking statements by terminology such as “may,” “will,” “should,” “expects,” “intends,” “plans,” anticipates,” “believes,” “estimates,” “predicts,” “projects,” “potential,” “continue,” and other similar terminology or the negative of these terms, but their absence does not mean that a particular statement is not forward-looking. Such forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that may cause actual results to differ materially from those anticipated by the forward-looking statements. These risks and uncertainties include, among others: that data from clinical trials may not necessarily be indicative of future clinical trial results; that the safety and/or efficacy profile for FOLOTYN may not support further clinical development in relapsed or refractory CTCL; and the risk that the Company may lack the financial resources and access to capital to fund future clinical trials for FOLOTYN. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Quarterly Report on Form 10-Q for the quarter ended September 30, 2010, and in the Company's other periodic reports and filings with the Securities and Exchange Commission. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this press release. All forward-looking statements are based on information currently available to the Company on the date hereof, and the Company undertakes no obligation to revise or update these forward-looking statements to reflect events or
circumstances after the date of this presentation, except as required by law.  
Note: The Allos logo and FOLOTYN name are trademarks of Allos Therapeutics, Inc.  
 Source: Allos Therapeutics, Inc.

1. Cutaneous Lymphoma Foundation. CTCL-MF fast facts.  Accessed November 14, 2010.

2. Romidepsin Reduces Disease Burden and Skin Symptoms in Patients with Previously Treated Cutaneous T-Cell Lymphoma. National Cancer Institute. Click here to read more. Accessed November 18, 2010.
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