Allos Therapeutics Announces Top Line Results from Pivotal Phase 2 PROPEL Trial of Pralatrexate in Patients with Relapsed or ...
December 07 2008 - 10:03AM
Business Wire
Allos Therapeutics, Inc. (Nasdaq:ALTH) today announced preliminary
top line results from PROPEL, the Company's pivotal Phase 2 trial
of pralatrexate (PDX) in patients with relapsed or refractory
peripheral T-cell lymphoma (PTCL), at the 50th Annual Meeting of
the American Society of Hematology (abstract 261). The results
according to central independent oncology review at the time of
this analysis are as follows: 29 of 109 evaluable patients (27%)
achieved either a complete or partial response 11 evaluable
patients had a complete response or complete response unconfirmed
18 evaluable patients had a partial response 23 evaluable patients
had stable disease as best response 3 patients had insufficient
data to assess response and 14 patients could not be assessed for
response because they discontinued treatment prior to completion of
cycle one. These patients are included in the evaluable patient
population for all efficacy analyses. The results according to the
PROPEL investigators at the time of this analysis are as follows:
42 of 109 evaluable patients (39%) achieved either a complete or
partial response 18 evaluable patients had a complete response or
complete response unconfirmed 24 evaluable patients had a partial
response 21 evaluable patients had stable disease as best response
Importantly, PROPEL patients received a median of three prior
systemic treatment regimens (range of 1-12), including 18 patients
(16%) who had previously undergone an autologous stem cell
transplant. Patient response evaluations will continue and all
patients will be followed for long-term survival. �The results of
the PROPEL trial demonstrate that pralatrexate produced durable,
complete responses in heavily pre-treated patients,� said Owen
O�Connor, M.D., Ph.D., the Principal Investigator of the PROPEL
trial and the Director of the Lymphoid Development and Malignancy
Program and Chief of the Lymphoma Service at the Herbert Irving
Comprehensive Cancer Center at New York-Presbyterian
Hospital/Columbia University Medical Center, and Associate
Professor of Medicine at Columbia University College of Physicians
and Surgeons. �Presently, there are no FDA-approved treatments for
patients with PTCL, either in the first-line or relapsed or
refractory setting. This underscores the need for new therapies to
treat this challenging disease. Pralatrexate has the potential to
play a clinically meaningful role in the treatment of these
patients.� �We are very excited by these results. Following our
review of the final results of the trial, we intend to submit an
NDA for pralatrexate for the treatment of patients with relapsed or
refractory PTCL in the first half of 2009. If approved, the launch
of pralatrexate will represent a first to market opportunity for
Allos,� said Paul L. Berns, President and Chief Executive Officer
of Allos. �We would like to extend our appreciation to the patients
who participated in the PROPEL trial, as well as to their families,
for helping us to identify a potential new treatment option for
this disease. I would also like to acknowledge our investigators
and employees for their commitment to this important study.� In the
trial, 69% of the patients who responded did so after cycle one of
therapy. The median duration of treatment in responding patients
was 179 days at the time of this analysis. The duration of response
exceeded three months in 17 of 29 responders (59%), including 6 of
the 17 patients who continued on treatment. An accurate estimate of
the median duration of response cannot be reported at this time due
to the current length of follow up. Patients will continue to be
followed until the median duration of response can be accurately
estimated. Following review of the final results of the trial, the
Company intends to submit a New Drug Application (NDA) to the U.S.
Food and Drug Administration (FDA) in the first half of 2009 to
seek marketing approval for pralatrexate for the treatment of
patients with relapsed or refractory PTCL. The most common grade
3/4 adverse events were thrombocytopenia, which was observed in 32%
of patients; mucosal inflammation in 21% of patients; neutropenia
in 20% of patients; and anemia in 18% of patients. �We are pleased
to share these data with the medical community. The results show
that pralatrexate, a novel targeted antifolate designed to
accumulate preferentially in cancer cells, achieved durable
responses, including complete responses, in patients with relapsed
or refractory peripheral T-cell lymphoma,� said Pablo J. Cagnoni,
M.D., Chief Medical Officer of Allos. �We believe pralatrexate has
the potential to offer a new treatment option for patients with
this devastating disease for which there are currently no approved
agents.� About PROPEL PROPEL (Pralatrexate in patients with
Relapsed Or refractory PEripheral T-cell Lymphoma) is a pivotal
Phase 2, international, multi-center, open-label, single-arm trial
that enrolled a total of 115 patients with relapsed or refractory
PTCL, 109 of whom are considered evaluable for response according
to the trial protocol. To the Company�s knowledge, the PROPEL trial
represents the largest prospectively designed single-agent trial
conducted to date in PTCL. To be eligible for the trial, patients
had to have progressed after at least one prior treatment. Patients
are considered evaluable if they received at least one dose of
pralatrexate and their diagnosis of PTCL was confirmed by
independent review. Patients receive 30 mg/m2 of pralatrexate
intravenously once every week for six weeks followed by one week of
rest per cycle of treatment. Patients also receive vitamin B12 and
folic acid supplementation. The primary endpoint of the trial is
objective response rate (complete and partial response), as
assessed by central independent oncology review using International
Workshop Criteria (IWC). Duration of response is the key secondary
endpoint. All patients enrolled in the trial will continue to be
followed for long-term survival. The PROPEL trial was initiated in
August 2006. In accordance with the PROPEL trial protocol, three
pre-planned interim analyses of safety data were previously
conducted. In January, September and December 2007, the Company
announced that an independent data monitoring committee (DMC)
completed interim analyses of safety data from the first 10, 35 and
65 evaluable patients who completed at least one cycle of treatment
with pralatrexate, respectively, and recommended that the trial
continue per the protocol at each analysis. The PROPEL trial is
being conducted under an agreement reached with the FDA under its
Special Protocol Assessment (SPA) process. The SPA process allows
for FDA evaluation of a clinical trial protocol intended to form
the primary basis of an efficacy claim in support of a NDA, and
provides an agreement that the trial design, including trial size,
clinical endpoints and/or data analyses are acceptable to the FDA.
The response rate, duration of response and safety profile required
to support FDA approval are not specified in the PROPEL trial
protocol and will be subject to FDA review. The FDA granted orphan
drug designation and fast track designation to pralatrexate for the
treatment of patients with T-cell lymphoma in July 2006 and
September 2006, respectively. In April 2007, the Commission of the
European Communities, with a favorable opinion of the Committee for
Orphan Medicinal Products of the European Medicines Agency, or
EMEA, granted orphan medicinal product designation to pralatrexate
for the treatment of patients with PTCL. About Pralatrexate (PDX)
Pralatrexate is a novel targeted antifolate designed to accumulate
preferentially in cancer cells. Based on preclinical studies, the
Company believes that pralatrexate selectively enters cells
expressing RFC-1, a protein that is over expressed on cancer cells
compared to normal cells. Once inside cancer cells, pralatrexate is
efficiently polyglutamylated, which leads to high intracellular
drug retention. Polyglutamylated pralatrexate essentially becomes
�trapped� inside cancer cells, making it less susceptible to
efflux-based drug resistance. Acting on the folate pathway,
pralatrexate interferes with DNA synthesis and triggers cancer cell
death.�The Company believes pralatrexate has the potential to be
delivered as a single agent or in combination therapy regimens.
About Peripheral T-cell Lymphoma Peripheral T-cell lymphomas, or
PTCLs, are a biologically diverse group of blood cancers that
account for approximately 10% to 15% of all cases of non-Hodgkin's
lymphoma (NHL) in the United States. According to the American
Cancer Society, approximately 66,000 patients are expected to be
diagnosed with NHL in the United States in 2008. The Company
estimates the current annual prevalence of PTCL at approximately
9,500 patients. There are currently no pharmaceutical agents
approved for use in the treatment of either first-line or relapsed
or refractory PTCL. In addition to the 30-50% of PTCL patients who
do not respond to first-line treatment, a significant number of
first-line multi-agent chemotherapy responders relapse or become
refractory after treatment. A study that included patients with
aggressive PTCL found that the average five-year survival for those
patients was approximately 25%. About Allos Therapeutics, Inc.
Allos Therapeutics is a biopharmaceutical company focused on
developing and commercializing innovative small molecule drugs for
the treatment of cancer.�The Company's lead product candidate,
pralatrexate (PDX), is a novel antifolate currently under
evaluation in a pivotal Phase 2 (PROPEL) trial in patients with
relapsed or refractory peripheral T-cell lymphoma. The Company
reported top line results from PROPEL in December 2008. Following
review of the final results of the trial, the Company intends to
submit a New Drug Application (NDA), for pralatrexate for the
treatment of patients with relapsed or refractory PTCL in the first
half of 2009. The PROPEL trial is being conducted under an
agreement reached with the U.S. Food and Drug Administration under
its special protocol assessment (SPA) process. The Company is also
investigating pralatrexate in patients with non-small cell lung
cancer, bladder cancer and a range of lymphoma sub-types.�The
Company's other product candidate�is RH1, a targeted
chemotherapeutic agent currently being evaluated in a Phase 1 trial
in patients with advanced solid tumors or non-Hodgkin�s lymphoma
(NHL). The Company currently retains exclusive worldwide rights to
pralatrexate and RH1 for all indications. For additional
information, please visit the Company�s website at www.allos.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 for pralatrexate to offer a new treatment option for
patients with relapsed or refractory PTCL, the Company�s intent and
projected timeline to submit a New Drug Application for
pralatrexate as a treatment for patients with relapsed or
refractory PTCL; 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 the PROPEL trial may not
demonstrate that pralatrexate is both safe and effective for the
treatment of patients with relapsed or refractory PTCL; that the
results of the PROPEL trial may not support an application for
marketing approval in the United States or any other country; that
an application for marketing approval may not be accepted for
priority review or at all by the FDA or any other regulatory
authority; and that the Company may lack the financial resources
and access to capital to fund future clinical trials for
pralatrexate or any of its other product candidates. 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 Annual Report on Form 10-K for the year
ended December 31, 2007 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.
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