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). In addition, the
Company reported preliminary results from its Phase 1/2 study of
FOLOTYN in combination with gemcitabine in patients with relapsed
or refractory lymphoproliferative malignancies. These data were
presented during a poster session at the 51st Annual Meeting of the
American Society of Hematology (ASH) in New Orleans, LA.
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).
FOLOTYN is the first and only drug approved by the FDA for this
indication and represents a new treatment option for 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.
The PROPEL posters included an update of overall response rate
for FOLOTYN as evaluated by independent central review using
International Workshop Criteria (IWC). Treatment with FOLOTYN
achieved an overall response rate of 29% (32 of 109 evaluable
patients). Sixty-three percent (63%) of patients responded within
the first cycle of therapy. Responses were durable with a median
duration of response of 10.1 months. Median overall survival was
14.5 months.
“FOLOTYN is an important new therapy for patients with relapsed
or refractory PTCL and for physicians who treat patients afflicted
with this very aggressive cancer,” said Owen A. O'Connor, M.D.,
Ph.D., principal 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. “We continue to be encouraged by the
observed responses in relapsed or refractory patients, including
those whose cancer never responded to a wide range of prior
therapies, including stem cell transplant therapy.”
Below is a summary of conclusions and key findings from the
poster presentations. To view the complete posters, go to the
Company’s web site and look under the “Presentations” tab of the
“Investor Relations” section of the website (www.allos.com).
PROPEL Poster Presentations
Abstract #1678 Pralatrexate Induces Responses in Patients with
Highly Refractory Peripheral T-Cell Lymphoma (PTCL)
A poster presentation by Dr. Kerry Savage, of the British
Columbia Cancer Agency, Vancouver, BC, Canada, characterized the
response to FOLOTYN among patients with peripheral T-cell lymphoma
in the PROPEL study who were considered to have refractory disease,
defined as no evidence of response to their most recent treatment
or to any prior therapies. Patients enrolled in PROPEL were a
heavily pretreated population who had a median of 3 prior systemic
therapies, with the most common being CHOP-based chemotherapy and
other multi-agent chemotherapy regimens. Eighteen patients (17%)
received autologous stem cell transplant prior to inclusion in the
study. The results of this analysis showed FOLOTYN produced durable
responses in patients with relapsed or refractory PTCL who had no
response to prior therapies, including the subpopulation of
patients who had no response to their most recent therapy as well
as patients who were refractory to all prior therapies.
- Of the 109 evaluable patients,
69 patients (63%) had no evidence of response to the most recent
prior therapy.
- According to central review,
these patients achieved a 25% (17/69) overall response rate, with a
duration of response ranging from 41 to 673 days. A 36% (25/69)
overall response rate was observed in these patients according to
investigator review.
- Among the 69 patients, 26
patients (24%) had no evidence of response to any prior therapy
before initiating FOLOTYN.
- According to central review, 5
(19%) of these patients responded to FOLOTYN with a duration
ranging from 54 to 306 days. Seven of these patients (27%)
responded according to investigator review.
- Additionally, 76 patients (68%)
received full dose FOLOTYN therapy at 30 mg/m2 despite heavy
pretreatment. Forty-six patients (67%) who had no response to their
most recent therapy received full-dose therapy at 30 mg/m2.
Abstract #1675 Safety and Management of Pralatrexate Treatment
in Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL)
A poster presentation by Dr. Lauren Pinter-Brown, of the
University of California at Los Angeles, CA, assessed the safety of
the patients included in PROPEL over three clinically important
parameters: duration of FOLOTYN treatment, early- and late-onset
FOLOTYN toxicities, and the impact of FOLOTYN dose modification on
toxicities. Overall, 115 patients were enrolled in the study. The
baseline and safety population included 111 patients who received
≥1 dose of FOLOTYN and excluded 4 patients not receiving therapy.
In the PROPEL trial overall safety population, the safety results
indicate that FOLOTYN was found to be well tolerated in patients
with PTCL.
- The 4 most commonly observed
adverse events were mucosal inflammation, nausea, thrombocytopenia
and fatigue.
- Despite a median of 3 prior
systemic therapies with potentially associated organ toxicities,
the majority of patients tolerated the full dose FOLOTYN of 30
mg/m2.
- The protocol-specified dose
modification schema effectively reduced the occurrence of mucosal
inflammation. Adherence to the FOLOTYN dose-modification guidelines
permitted continued FOLOTYN therapy.
- The most common Grade 3-4 AEs
for patients who initiated cycle 3 were observed at similar or
lower rates compared to those observed in cycles 1-2. These data
suggest that there is no cumulative-dose toxicity with FOLOTYN,
which permits continued therapy for patients who derive benefit
from FOLOTYN.
Abstract #1681 Correlation Between Baseline Methylmalonic Acid
Status and Mucositis Severity in the PROPEL Study: Implications for
Vitamin Prophylaxis
A poster presentation by Dr. Barbara Pro, of the University of
Texas M.D. Anderson Cancer Center, Houston, TX, assessed baseline
methylmalonic acid (MMA) status, homocysteine (HCY), and red blood
cell (RBC) folate levels in patients enrolled in PROPEL. This
baseline and safety population included 111 patients who received
≥1 dose of FOLOTYN and excluded 4 patients not receiving therapy.
The analysis was conducted to determine if there was an association
between these values and mucosal inflammation and thrombocytopenia
observed in the study.
- The maximum mucosal inflammation
grade experienced during FOLOTYN therapy (Grade 0 vs Grade 1-2 vs
Grade 3-4) and the baseline MMA value had a statistically
significant linear relationship (p=0.039).
- The analysis revealed no other
significant relationship; and baseline HCY and RBC folate values
were not predictive of the severity of mucositis or
thrombocytopenia in this assessment.
- There was also a trend toward a
relationship between increasing MMA and increasing severity of
thrombocytopenia but did not meet statistical significance
(p=0.267).
- Based on these results, vitamin
supplementation of folic acid and vitamin B12 is appropriate with
FOLOTYN administration for relapsed or refractory PTCL.
FOLOTYN and Gemcitabine Study Poster Presentation
Abstract #1674 Pralatrexate and Gemcitabine in Patients with
Relpased or Refractory Lymphoproliferative Malignancies: Phase 1
Results
A poster presentation by Dr. Steven M. Horwitz, of Memorial
Sloan-Kettering Cancer Center, New York, NY, reviewed preliminary
results from a Phase 1/2 study of FOLOTYN and gemcitabine in
patients with B-cell lymphoma, PTCL and Hodgkin’s disease. The
primary objective of the Phase 1 dose finding portion of this study
was to evaluate the safety and preliminary efficacy of the
combination of FOLOTYN and gemcitabine. The Phase 1 evaluation
determined the maximum tolerated dose (MTD) of the combination of
FOLOTYN and gemcitabine on sequential days and same day schedules.
Patients were administered a combination of FOLOTYN and gemcitabine
according to three regimens: on the same day every two weeks (q2w),
on sequential days q2w, or on sequential days once weekly for three
weeks of a four week cycle.
- These data demonstrated that
treatment with FOLOTYN and gemcitabine is feasible, with acceptable
toxicity, when administered on a q2w schedule.
- The dose administered of each
drug is higher when given on the same day schedule as compared to
treating on sequential day schedule.
- In this dose ranging study,
preliminary results showed activity of the combination of FOLOTYN
and gemcitabine in lymphoid malignancies with a 24% overall
response rate in this heavily pretreated population.
- The Phase 2 expansion at the MTD
will evaluate both sequential and same-day dosing of FOLOTYN in a
q2w schedule.
About PROPEL
The open-label, single-arm, multicenter, international Phase 2
clinical trial is the largest prospective study of its type ever
conducted in patients with relapsed or refractory PTCL. PROPEL
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
(complete response, complete response unconfirmed and partial
response) 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.
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 (1.0 -1.25 mg
orally on a daily basis) and receive vitamin B12 (1 mg
intramuscularly every 8-10 weeks) 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.
Adverse Reactions:The most common adverse reactions
observed in PROPEL were mucositis (70%), thrombocytopenia (41%),
nausea (40%), and fatigue (36%). The most common serious
adverse events (>3%), regardless of causality, were pyrexia,
mucositis, sepsis, febrile neutropenia, dehydration, dyspnea and
thrombocytopenia. Forty-four percent of patients experienced a
serious adverse event while on study or within 30 days after their
last dose of FOLOTYN. Twenty-three percent of patients discontinued
treatment due to adverse reactions.
Drug Interactions:Co-administration of drugs subject to
renal clearance (e.g., probenecid, NSAIDs, and
trimethoprim/sulfamethaxazole) may result in delayed renal
clearance.
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.
For additional important safety information, please see the full
prescribing information for
FOLOTYN at www.allos.com.
About Peripheral T-cell Lymphoma
Peripheral T-cell lymphomas (PTCL) are a diverse group of
aggressive T-cell and natural killer (NK)-cell non-Hodgkin’s
lymphomas (NHL) that account for approximately 10% to 15% of all
newly diagnosed cases of NHL in the United States.1-3 The American
Cancer Society estimates that approximately 66,000 new cases of NHL
were diagnosed in the U.S. in 2009. The Company estimates the
current annual incidence of PTCL in the U.S. to be approximately
5,600 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 for patients
with PTCL is 25% to 40%, depending on sub-type.4-5
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 exploring the potential of FOLOTYN in other
indications. Allos retains exclusive worldwide rights to FOLOTYN
for all indications. Allos is headquartered in Westminster, CO. 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 FOLOTYN
to play a clinically meaningful role in the treatment of patients
with relapsed or refractory PTCL; the potential for FOLOTYN to be
an effective treatment option 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. Important factors
that may cause actual results to differ materially include, but are
not limited to, the risks and uncertainties associated with
developing adequate sales, marketing and distribution capabilities;
the acceptance of FOLOTYN in the marketplace; the status of
reimbursement from third party payers; the Company’s dependence on
third party manufacturers; the Company’s compliance with applicable
regulatory requirements, including the healthcare fraud and abuse
laws and the Company’s post-marketing requirements; and the
Company’s access to capital to support its future operations,
including product development and commercialization plans 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, 2009, 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.
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.
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