WESTMINSTER, Colo.--(BUSINESS WIRE)--Mar. 25, 2009--
Allos Therapeutics, Inc. (NASDAQ: ALTH) today announced that it has
submitted a New Drug Application (NDA) to the U.S. Food and Drug
Administration (FDA) for the use of pralatrexate for the treatment of
patients with relapsed or refractory peripheral T-cell lymphoma (PTCL).
The Company has requested a priority review of the application, which,
if granted, would give the FDA six months from receipt of the submission
to take action on the application. PTCL comprises a biologically diverse
group of hematologic malignancies that typically has a worse prognosis
than other types of lymphoma and is less responsive to traditional
chemotherapy regimens. There are currently no agents approved by the FDA
for the treatment of patients with PTCL.
“The NDA submission is based on the encouraging efficacy and safety data
we reported earlier this year with pralatrexate in patients with
relapsed or refractory PTCL,” said Paul L. Berns, president and chief
executive officer of Allos Therapeutics, Inc. “We plan to work closely
with the FDA to facilitate the completion of their review as
expeditiously as possible. There are currently no agents approved by the
FDA for the treatment of patients with PTCL, which demonstrates the
clear, high-unmet need for new therapies to treat patients with this
devastating disease. If approved, pralatrexate represents a potential
first-to-market opportunity for Allos and could be the first agent
approved by the FDA for the treatment of patients with relapsed or
refractory PTCL.”
The NDA is based on the results from the Company’s pivotal Phase 2 trial
known as PROPEL (Pralatrexate in patients with Relapsed Or
refractory PEripheral T-cell Lymphoma). The PROPEL trial
was conducted under an agreement reached with the FDA under its Special
Protocol Assessment, or SPA, process. Pralatrexate has orphan drug
designation and fast track designation in the U.S. for the treatment of
patients with T-cell lymphoma and orphan medicinal product designation
in Europe for the treatment of PTCL. The Company believes the PROPEL
trial is the largest prospectively designed single-agent trial conducted
to date in patients with relapsed or refractory PTCL.
About PROPEL
This pivotal Phase 2 international, multi-center, open-label, single-arm
trial 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 be eligible for the trial, patients’ disease must
have progressed after at least one prior treatment. Patients were
considered evaluable if they received at least one dose of pralatrexate
and their diagnosis of PTCL was confirmed by independent pathology
review. Patients received 30 mg/m2 of pralatrexate
intravenously once every week for six weeks followed by one week of rest
per cycle of treatment. Patients also received vitamin B12
and folic acid supplementation. The primary endpoint of the trial is
objective response rate, as assessed by central independent oncology
review using International Workshop Criteria (IWC). Duration of response
is the key secondary endpoint.
In February 2009, the Company announced final results from the PROPEL
trial. Twenty-nine of 109 evaluable patients, or 27 percent, achieved a
response as assessed by central independent oncology review, which is
the primary endpoint of the trial. The Kaplan-Meier estimate for the
median duration of response was 287 days, or 9.4 months. Duration of
response is the key secondary endpoint of the trial. The most common
grade 3/4 adverse events were thrombocytopenia, which was observed in 32
percent of patients; mucosal inflammation in 21 percent of patients;
neutropenia in 20 percent of patients; and anemia in 17 percent of
patients. The results of the trial will be submitted for presentation at
an upcoming scientific meeting and for publication in a peer-reviewed
journal.
Of the 29 patients who achieved a response according to central
independent oncology review, 7 patients had a complete response (CR), 2
patients had a complete response unconfirmed (CRu) and 20 patients had a
partial response (PR). Responses were also assessed by the PROPEL
investigators, who determined that 42 of 109 evaluable patients, or 39
percent, achieved a response. Of these, 15 patients had a CR, 4 patients
had a CRu and 23 patients had a PR. PROPEL patients received a median of
three prior systemic treatment regimens (range of 1-12), including 18
patients, or 16 percent, who had previously undergone an autologous stem
cell transplant. In the trial, 66 percent of the patients who responded
did so after cycle one of therapy. Patients will continue to be followed
for long-term survival.
The PROPEL trial is being conducted under an agreement reached with the
FDA under its 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 an 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. In addition, the median duration of response reported above is a
Kaplan-Meier estimate based on the length of follow up for all
responders at the time the PROPEL trial database was locked. As a
result, the median duration of response may change based on continued
patient follow-up.
About Peripheral T-cell Lymphoma
PTCL comprises a biologically diverse group of hematologic malignancies
that accounts for approximately 10 to 15 percent of non-Hodgkin’s
lymphoma, or NHL, cases in the U.S. The American Cancer Society
estimated that 66,000 new cases of NHL were diagnosed in the U.S. in
2008. The Company estimates the current annual prevalence of PTCL in the
U.S. to be approximately 9,500 patients. No pharmaceutical agents are
currently approved for use in the treatment of either first-line or
relapsed or refractory PTCL. In addition to those 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. According to the clinical literature, patients with
aggressive PTCL have an overall five-year survival rate of approximately
25 percent after first-line therapy.
About Pralatrexate
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 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, is a novel
targeted antifolate designed to accumulate preferentially in cancer
cells. In February 2009, the Company announced the final results from
PROPEL, the Company’s pivotal Phase 2 trial of pralatrexate in patients
with relapsed or refractory peripheral T-cell lymphoma (PTCL). The
PROPEL trial was conducted under an agreement reached with the U.S. Food
and Drug Administration (FDA) under its Special Protocol Assessment
process. Based on the results of the PROPEL trial, in March 2009 the
Company submitted a New Drug Application to the FDA for the use of
pralatrexate for the treatment of patients with relapsed or refractory
PTCL. The Company is investigating pralatrexate in patients with
peripheral T-cell lymphoma, non-small cell lung cancer, bladder cancer
and a range of lymphoma sub-types; and it currently retains exclusive
worldwide rights to pralatrexate for all indications. For additional
information, please visit 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 be first agent
approved by the FDA for the treatment of 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 design of
or data collected from the PROPEL trial may not be adequate to
demonstrate the safety and efficacy of pralatrexate for the treatment of
patients with relapsed or refractory PTCL, or otherwise be sufficient to
support FDA approval; that the Company’s New Drug Application may not be
accepted for priority review or at all by the FDA; that the FDA may
disagree with the Company’s interpretations of data from preclinical
studies and clinical trials involving pralatrexate, including the PROPEL
trial, or otherwise determine such data are not sufficient to support
approval; that the Company may experience difficulties or delays in the
initiation, progress or completion of its clinical trials, whether
caused by competition, adverse events, investigative site initiation
rates, patient enrollment rates, regulatory issues or other factors; and
that the Company may lack the financial resources and access to capital
to support its future operations, including the potential
commercialization of pralatrexate if approved for marketing. 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 Dec. 31,
2008, 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.
Source: Allos Therapeutics, Inc.
Allos Therapeutics, Inc.
Monique Greer, 303-426-6262
mgreer@allos.com
