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Data Shows Activity of FOLOTYN® in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma Following Treatment with CHOP

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LUGANO, Switzerland--(BUSINESS WIRE)--

Allos Therapeutics, Inc. (Nasdaq: ALTH) today reported results from a retrospective analysis of data from the Company's pivotal PROPEL trial, which assessed the safety and efficacy of single-agent FOLOTYN® (pralatrexate injection) as a second-line treatment in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who received CHOP as their first-line treatment. Data were presented at the 11th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (June 15-18).

CHOP (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) is the most common first-line therapy for PTCL. However, the majority of patients progress within 6-12 months following treatment with CHOP and there is currently no standard of care for second-line treatment.

“These results demonstrate the ability of FOLOTYN to achieve responses in a significant proportion of patients with peripheral T-cell lymphoma who have not responded to, or relapsed, following their initial treatment with CHOP,” said Andrei Shustov, M.D., Assistant Professor of Medicine at the University of Washington, investigator on the PROPEL trial. “Further research is warranted to assess whether the activity and responses observed in this exploratory analysis with FOLOTYN may lead to increased options for patients, including stem cell transplantation approaches – which are currently considered the only curative option for some T-cell lymphomas.”

PROPEL enrolled 115 patients, 109 of whom were considered evaluable for efficacy according to the trial protocol. Study endpoints included overall response rate – defined as complete response, unconfirmed complete response, and partial response – as well as duration of response, progression-free survival, and overall survival. Of the 15 evaluable patients who received FOLOTYN as a second-line treatment post-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.
  • Complete responses – meaning there was a complete regression of all signs of disease in response to treatment with FOLOTYN – were observed in three of the 15 patients (20%), based on independent central review, and four of the 15 patients (27%), based on local investigator review.
    • Two of these patients went on to receive a stem cell transplant after responding to FOLOTYN and sustained complete responses for 20.9 and 27.2 months through the time of last contact.
  • Median duration of response, by independent central review, had not yet been reached at the time of analysis; by local investigator review, the median duration of response was 12.5 months.
  • Progression-free survival was 8.1 months by independent central review and 7.4 months per local investigator review.
  • Median overall survival was not able to be estimated as 11 (75%) of the 15 patients were still alive at the time of last contact; the 12-month overall survival estimate was 73 percent.

The demographics and disease characteristics for this subgroup of 15 patients were reflective of the overall PROPEL patient population. FOLOTYN was well-tolerated in this patient population. The most common Grade 3 adverse events were mucositis (20%) and thrombocytopenia (27%). The most common Grade 2 adverse events were mucositis (40%), and nausea (7%). The only Grade 4 adverse event was sepsis occurring in 1 patient (7%). Two of the 15 patients discontinued treatment due to drug-related toxicity (1 due to mucositis; 1 due to pneumonitis).

“Subsequent analyses of data from the PROPEL trial continue to demonstrate that FOLOTYN is effective as a single agent and should be considered as a second-line therapeutic option for patients with relapsed or refractory peripheral T-cell lymphoma,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics. “Specifically, the activity of FOLOTYN observed in this analysis further supports the design of our planned Phase 3 trial – sequential FOLOTYN in previously untreated patients with peripheral T cell lymphoma following treatment with CHOP/CHOP-like regimen – which has the potential to expand the clinical utility of FOLOTYN into the first-line treatment setting.”

FOLOTYN, a folate analogue metabolic inhibitor, is the only drug approved in the U.S. for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (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. In December 2010, Allos announced that the Company's Marketing Authorisation Application (MAA), seeking approval of FOLOTYN for the treatment of patients with relapsed or refractory PTCL, was accepted for review by the European Medicines Agency (EMA).

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.

An updated analysis of data from PROPEL was recently published in the March 20, 2011 issue of the Journal of Clinical Oncology.

About Peripheral T-Cell Lymphoma

Peripheral T-cell lymphomas are a biologically diverse group of aggressive, mature T and NK (natural killer) cell non-Hodgkin lymphomas with similar outcomes, which include PTCL-NOS (PTCL not otherwise specified), AITL (angioimmunoblastic T-cell lymphoma), and ALCL (anaplastic large-cell lymphoma).1 The prognosis for patients with PTCL is generally poor for most subtypes.2

T-cell lymphomas account for approximately 10% to 15% of all cases of non-Hodgkin lymphomas (NHL).1-3 Allos estimates the current annual incidence of PTCL to be approximately 5,900 patients in the U.S. and approximately 6,000-7,000 patients in the top five European markets. 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 approved in the U.S. for the treatment of patients with relapsed or refractory PTCL. Allos is also developing FOLOTYN in other hematologic malignancies and solid tumors. 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.

Fatal dermatologic reactions may occur. Dermatologic reactions may be progressive and increase in severity with further treatment. Patients with dermatologic reactions should be monitored closely, and if severe, FOLOTYN should be withheld or discontinued.

Tumor lysis syndrome may occur. Monitor patients and treat if needed.

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.

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 peripheral 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 peripheral 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 March 31, 2011, 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.       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.
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. Savage KJ. Peripheral T-cell Lymphomas. Blood Rev. 2007; 21:201-216.

Allos Therapeutics
Monique Greer 720-540-5268
mgreer@allos.com
or
Madeline Malia, 609-454-0325
mmalia@allos.com

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