About Cutaneous Lymphoma

Allos Therapeutics Reports New Analyses of FOLOTYN® Data from PROPEL trial in Relapsed or Refractory Peripheral T-Cell Lymphoma

Sat, 12/04/2010

Allos Therapeutics Reports New Analyses of FOLOTYN® Data from PROPEL trial in Relapsed or Refractory Peripheral T-Cell Lymphoma
 
- Data presented at 52nd American Society of Hematology Annual Meeting -
 
ORLANDO, Fla., & WESTMINSTER, Colo., – December 4, 2010 – 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) at the 52nd American Society of Hematology (ASH) Annual Meeting held in Orlando, Florida.
 
Results from three new retrospective analyses of single-agent FOLOTYN showed:  
 Of the patients who received prior „ICE‟ or similar aggressive combinations (primarily used for salvage treatment of PTCL) (n=20), objective responses were observed in eight patients (40%) treated with FOLOTYN as assessed by independent central review.  These results indicate activity of FOLOTYN in patients with relapsed or refractory PTCL who received prior ICE-based chemotherapy.   

 
 Of the patients whose disease progressed following treatment with first-line „CHOP‟ therapy (n=15), objective responses were observed in seven patients (47%) treated with FOLOTYN as assessed by independent central review.  These results indicate activity of FOLOTYN in the second-line treatment setting following CHOP for patients with relapsed or refractory PTCL.  

 
 Of the patients who received three or more systemic therapies prior to enrolling in the PROPEL trial (n=57), objective responses and progression-free survival decreased with each line of therapy prior to FOLOTYN.  Following treatment with FOLOTYN, responses and progression-free survival increased relative to the immediate prior line of therapy, thus reversing the trend of progressive resistance.  

 
“These analyses demonstrate the ability of FOLOTYN to achieve responses in patients in the second-line treatment setting immediately following treatment with CHOP, and indicate that FOLOTYN may be an effective treatment option in patients who have progressed after aggressive chemotherapy regimens such as ICE,” said Owen A. O’Connor, M.D., Ph.D., principal investigator in the PROPEL study; 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. “These analyses also suggest that FOLOTYN may reverse the pattern of progressive resistance in patients with drug-resistant peripheral T-cell lymphoma.”  
 
“Allos is pleased that PROPEL has and continues to provide important insights into the role of FOLOTYN to treat patients with relapsed or refractory peripheral T-cell lymphoma – which is a devastating disease,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics.  
Below is a summary of conclusions and key findings from the new analyses of data from the pivotal PROPEL trial– which enrolled 115 patients, 109 of whom were considered evaluable for efficacy according to the trial protocol.  Study endpoints included overall response rate (ORR) – defined as complete response, unconfirmed complete response, and partial response – as well as duration of response (DoR), progression-free survival (PFS), and overall survival (OS).  ORR, DoR and PFS were evaluated by independent central review using International Workshop Criteria (IWC).   
Poster #1753: Pralatrexate is Effective in Patients with Relapsed/Refractory Peripheral T-cell Lymphoma (PTCL) After Progression Following Prior Ifosfamide, Carboplatin, and Etoposide (ICE)-based Regimens
 
A poster presentation by Dr. Andre Goy of The John Theurer Cancer Center at Hackensack University Medical Center assessed the efficacy of FOLOTYN in patients with PTCL whose disease progressed following prior treatment with an ICE-based regimen (n=20).  Results of this analysis indicate activity of FOLOTYN in patients with relapsed or refractory PTCL who received prior ICE-based chemotherapy.   
 
Prior to enrolling in PROPEL, response to ICE-based therapy was observed in five of 20 patients (25%).  Of those patients whose disease progressed following prior ICE-based chemotherapy, objective responses with FOLOTYN were observed in eight of 20 patients (40%), including several patients who did not respond to ICE-based therapy; these results were consistent across independent central review and local investigator review.  Three of the 20 patients (15%), based on independent central review, and five of the 20 patients (25%), based on local investigator review, experienced complete response; two patients went on to receive a stem cell transplant, which may result in long-term remissions in some patients.  The median duration of response to FOLOTYN was 13.1 months per independent central review and 16.2 per local investigator review.  The safety profile observed in these patients was consistent with that observed in the overall PROPEL study.  The most common non-hematologic Grade 3-4 adverse event observed in these patients was mucositis (30%); the most common hematologic Grade 3-4 adverse events were anemia (45%) and thrombocytopenia (40%).  
 
Abstract #4882: Pralatrexate is Effective as Second-line Treatment Following Cyclophosphamide/Doxorubicin/Vincristine/Prednisone (CHOP) Failure in Patients with Relapsed or Refractory Peripheral T-cell Lymphoma (PTCL)
 
This analysis by Dr. Andrei Shustov of Seattle Cancer Care assessed the efficacy of FOLOTYN as a second-line treatment in patients with PTCL whose disease progressed following first-line treatment with CHOP.   Although CHOP is the most common therapy for first-line treatment of PTCL, most patients progress within 6 to 12 months and there is no standard of care for second-line treatment.   Results of this analysis indicate activity of FOLOTYN in the second-line treatment setting following CHOP for patients with relapsed or refractory PTCL.     
 
Of the 15 evaluable patients in the PROPEL study whose disease progressed following first-line treatment with CHOP, objective responses with FOLOTYN were observed in seven patients (47%) as assessed by independent central review and in six patients (40%) as assessed by local investigators.  Three of the 15 patients (20%), based on independent central review, and four of the 15 patients (27%), based on local investigator review, experienced a complete response; two of these patients went on to receive a stem cell transplant and sustain complete responses for 20.1 and 21.7 months.  The median duration of response to FOLOTYN was 12.5 months per local investigator review; by independent central review, the median duration of response had not yet been reached.    
 
Abstract #4881: Pralatrexate Reverses the Trend to Progressive Resistance to Successive Systemic Treatment Regimens in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL)
 
This analysis by Dr. Owen O‟Connor of the NYU Langone Medical Center was conducted to determine whether a trend of progressive resistance is observed in patients with relapsed or refractory PTCL, as well as to assess the potential ability of FOLOTYN to overcome drug resistance.   Progressive resistance – characterized by a continual decrease of responses and progression-free survival in patients in the second-line treatment setting and then with each subsequent therapy – is often observed in hematologic malignancies and solid tumors.  Results of this analysis demonstrated, for the first time, that patients with PTCL exhibit the same pattern of progressive drug resistance observed in other tumor types.  This analysis also showed that following treatment with FOLOTYN, response rates and progression-free survival increased relative to the immediate prior line of therapy, thus reversing the trend of progressive resistance.
 
Of the 57 patients who received three lines of therapy or more prior to enrolling in the PROPEL trial, objective responses and progression-free survival decreased with each line of treatment – with response rates decreasing from 56 percent (32 of 57 patients) to 30 percent (17 of 57 patients) and progression-free survival decreasing from 213 days to 95 days.  Following treatment with FOLOTYN, response rates and progression-free survival increased to 40 percent (23 of 57 patients) and 134 days, respectively.    
 
As principal investigator of the PROPEL study, Dr. O‟Connor receives research funding for studies of FOLOTYN from Allos Therapeutics.  
 
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.1-3The 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 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.  
 
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 future development of FOLOTYN for the treatment of patients with T-cell lymphoma or any other type of cancer; 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 preclinical studies and 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 patients with T-cell lymphoma or any other type of cancer; 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.
 
# # #
 
References:
 
1. Savage KJ. Peripheral T-cell Lymphomas. Blood Rev. 2007; 21:201-216.
2. Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update [review]. Lancet Oncol. 2004;5(6):341-353.
3. O'Leary HM, Savage KJ. Novel therapies in peripheral T-cell lymphomas [review]. Curr Oncol Rep. 2008;134(5):202-207.
4. 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.
5. 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.