ALTH Allos Therapeutics, Inc. (MM)

Allos Therapeutics, Inc. (NASDAQ: ALTH) today announced that the Journal of Clinical Oncology has published data from the Company’s pivotal Phase 2 PROPEL study demonstrating clinical activity of FOLOTYN® (pralatrexate injection) in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). These published results are from an updated analysis of the PROPEL study, which was the basis of the September 2009 U.S. Food and Drug Administration (FDA) accelerated approval of FOLOTYN – the only single-agent approved 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.

PTCL is 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 PTCL is often initially treated with multi-agent systemic chemotherapy; however, the majority of patients ultimately develop relapsed or refractory disease.1 The prognosis for patients with PTCL is generally poor for most subtypes.2

“Data from PROPEL demonstrate the role of FOLOTYN as a single-agent treatment for patients with peripheral T-cell lymphoma whose disease is no longer responding to initial chemotherapy,” said Owen A. O’Connor, M.D., Ph.D., principle 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. “Although patients enrolled in this trial received a median of three – and up to 12 – prior therapies, it is particularly impressive that we still observed a compelling overall response rate, with durable responses – an important measure of activity for this agent.”

Results of the published PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) study show an overall response rate (complete response (CR), complete response unconfirmed (CRu), and partial response (PR)) of 29 percent (n=32) observed in patients treated with FOLOTYN, as assessed by independent central review using International Workshop Criteria (IWC); eleven percent (n=12) of patients treated with FOLOTYN experienced a CR or CRu, which means there was a complete disappearance of all signs of disease in response to treatment with FOLOTYN. Responses were also assessed by the PROPEL investigators.

         

 

 

Independent Central Review N=109 evaluable (percent)

 

Investigator Review N=109 evaluable (percent)

Overall response rate (CR+Cru+PR)   32 (29%)   43 (39%)

Complete response/complete response unconfirmed (CR/CRu)

  12 (11%)   20 (19%) Partial response (PR)   20 (18%)   23 (21%) Stable disease (SD)   21 (19%)   21 (19%) Median duration of response  

10.1 months; 306 days

  8.1 months; 246 days    

As assessed by the independent central review, of the 69 patients who did not have any evidence of response to their most recent prior therapy, 25 percent (n=17) responded to FOLOTYN; of the 26 patients who did not have evidence of response to any prior conventional therapy, 19 percent (n=5) responded to FOLOTYN. Sixty-three percent of all responses occurred within the first cycle of FOLOTYN. The median overall survival was 14.5 months with a range of one month to 24 months after a median follow-up of 18 months; median progression-free survival was 3.5 months with a range of one day to 23.9 months. 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.

The most common Grade 3-4 adverse events observed were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%). See below for Important Safety Information.

“As the only treatment approved for patients with relapsed or refractory peripheral T-cell lymphoma, FOLOTYN is an important addition to the treatment paradigm for this aggressive form of T-cell lymphoma,” said Charles Morris, MB ChB, MRCP, chief medical officer at Allos Therapeutics. “The strength of the results from the pivotal PROPEL study add to the growing body of data demonstrating that FOLOTYN is an effective treatment option for patients with relapsed or refractory peripheral T-cell lymphoma. As part of our ongoing commitment to the medical community and patients, we are exploring the potential of FOLOTYN as a single-agent and in combination with other therapies in a variety of hematologic malignancies, including first-line PTCL and relapsed or refractory cutaneous T-cell lymphoma.”

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 six weeks in 7-week cycles until disease progression or unacceptable toxicity. In addition, patients received 1 mg 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.

As principal investigator of the PROPEL study, Dr. O’Connor receives research funding for studies of FOLOTYN from Allos Therapeutics.

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.4-6 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.3-4

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.

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.

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

Source: Allos Therapeutics, Inc.

References

1.  

Getting the Facts, Peripheral T-Cell Lymphoma, Lymphoma Research Foundation, 2009. http://www.lymphoma.org/atf/cf/%7B0363cdd6-51b5-427b-be48-e6af871acec9%7D/PTCL09.PDF. Accessed 11/4/10.

2.

Transplantation for Non-Hodgkin Lymphoma: Auto-HCT for Peripheral T-cell Lymphoma. Medscape Today. http://www.medscape.com/viewarticle/708405_12. Accessed 11/4/2010.

3.

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.

4. Savage KJ. Peripheral T-cell Lymphomas. Blood Rev. 2007;21:201-216.

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.

5. Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin lymphoma: an update [review]. Lancet Oncol. 2004;5(6):341-353. 6. O'Leary HM, Savage KJ. Novel therapies in peripheral T-cell lymphomas [review]. Curr Oncol Rep. 2008;134(5):202-207.