Healthcare Industry News: CLL
News Release - May 31, 2006
Vion Pharmaceuticals Provides Update for Clinical and Preclinical Programs
Company Also Reports on Initial Commercialization Efforts for Cloretazine(R)NEW HAVEN, Conn., May 31 (HSMN NewsFeed) -- VION
PHARMACEUTICALS, INC. (Nasdaq: VION) today provided an update on its
clinical and preclinical programs, and its initial commercialization
efforts for Cloretazine(R) (VNP40101M).
Conference Call Notification
Vion will host a conference call today at 8:45 a.m. eastern time. The
conference can be accessed by dialing (800) 510-0178 in the U.S. ((617)
614-3450 for international callers), pass code 56955938 at least fifteen
minutes before the start of the call. The conference call will also be
webcast simultaneously and will be accessible on Vion's website,
http://www.vionpharm.com. A replay of the call will be available at (888) 286-8010
in the U.S. ((617) 801-6888 for international callers), pass code 72021198
through June 26, 2006.
Cloretazine(R) (VNP40101M) in Acute Myelogenous Leukemia
Vion's lead anticancer agent, the novel alkylating agent Cloretazine(R)
(VNP40101M), is now being evaluated in two pivotal trials in acute
myelogenous (AML). Last week, the Company announced that it had initiated a
pivotal Phase II trial of single agent Cloretazine(R) (VNP40101M) in
elderly patients with de novo poor-risk AML. This trial is in addition to
the ongoing Phase III study of Cloretazine(R) (VNP40101M) in combination
with Ara-C for patients with relapsed AML.
Phase III Trial in Patients with Relapsed AML
The Company's randomized placebo-controlled Phase III trial (CLI-037)
of Cloretazine(R) (VNP40101M) is being conducted in relapsed AML, in
patients of any age with initial remissions of at least three months and
not more than twenty-four months. The trial randomizes patients in a 2:1
fashion (experimental arm : control arm). Patients are also stratified
according to (x) age (greater than or less than 60 years of age) and (y)
the length of their first remission (greater than or less than one year).
Patients receive either (i) 1.5 grams of Ara-C in a continuous infusion
over three days and 600 mg/m(2) of Cloretazine(R) (VNP40101M) or (ii) 1.5
grams of Ara-C in a continuous infusion over three days and placebo.
Patients may receive a second course of induction therapy if their disease
is improving but they have not achieved a complete remission. If they
achieve remission, patients may also receive consolidation therapy. The
primary endpoint for this study is the complete remission rate including
CRp (a complete remission with incomplete recovery of platelet count);
secondary endpoints are time-to-progression, duration of response, overall
survival and toxicity. The study is designed to demonstrate with sufficient
power a 15% higher complete remission rate in the experimental arm over the
control arm (i.e., a 45% remission rate in the experimental arm versus 30%
in the control arm).
The Company reported that there are over 140 patients enrolled on this
Phase III study, which is now open in 65 sites in North America and Europe.
An interim analysis is planned when 210 patients have been evaluated for
response. This accrual milestone is expected to be reached in the second
half of 2006. The data will be made available to the Data Safety and
Monitoring Board as soon as possible thereafter. The trial is designed to
accrue 420 patients in total, which the Company expects to be completed in
2007.
Phase II Trial in Elderly Patients with De Novo Poor-Risk AML
Last week, the Company initiated a pivotal Phase II trial (CLI-043) in
elderly patients with de novo poor-risk AML. This trial is expected to be
conducted in approximately 20 sites in North America and Europe. Full
accrual of the targeted 85 patients is expected to take up to one year.
De novo AML has not resulted from a prior documented myelodysplastic
syndrome nor from a previous exposure to chemotherapy or radiotherapy.
Elderly poor-risk AML is associated with certain risk factors in an older
patient that make it unlikely that the patient will respond to or tolerate
standard induction therapy. In CLI-043, patients are required to be over
the age of 60 with previously untreated de novo AML and at least one
additional risk factor from the following list: (i) ECOG performance status
of 2 or greater; (ii) unfavorable cytogenetics; and (iii) significant
cardiac, pulmonary, or hepatic dysfunction such that patients could not
receive standard induction therapy. Alternatively, patients must be 70
years of age or older with previously untreated de novo AML and without
favorable cytogenetics.
Ms. Cahill stated, "We have designed CLI-043 to confirm the data from
our previous Phase II trial (CLI-033) in a prospectively defined elderly
poor-risk AML patient population. We are confident that the patient
inclusion criteria for this new trial define the unmet medical need patient
population in AML."
Patients will receive 600 mg/m(2) of Cloretazine(R) (VNP40101M) in a
30-60 minute infusion and may receive a second course of induction therapy
if their disease is improving but they have not achieved a remission.
Patients who respond will receive consolidation with Ara-C.
The primary endpoint for the trial is the complete remission rate
including CRp and the secondary endpoints are durability of response,
progression-free survival and overall survival. The trial is designed in
two stages. If 8 complete remissions are documented in the first 42
patients enrolled, the study will proceed to the second stage.
In conjunction with this trial, Vion will also conduct additional
correlative studies and collect health resource utilization data. The
correlative studies include molecular analysis of AML cells, levels of a
drug resistance enzyme, and appropriate pharmacokinetic data of
Cloretazine(R) (VNP40101M).
The Company will be presenting data from the recently completed CLI-033
on Cloretazine(R) (VNP40101M) in de novo AML in a poster discussion session
at the Annual Meeting of the American Society of Clinical Oncology (ASCO)
in Atlanta, Georgia on June 4, 2006.
Cloretazine(R) (VNP40101M) in Other Indications
In addition to its work in AML, the Company has been conducting trials
of Cloretazine(R) (VNP40101M) in small cell lung cancer (Phase II) and
chronic lymphocytic leukemia (CLL) (Phase I/II), as well as a trial (Phase
I) of Cloretazine(R) (VNP40101M) in combination with temozolomide in
advanced hematologic malignancies.
The Company announced that anti-tumor activity had been reported in the
Phase II trial in small cell lung cancer. Although no significant organ
toxicity has been reported, the protocol is being amended to reduce the
dose of Cloretazine(R) (VNP40101M) so that patients may be able to receive
multiple cycles without significant hematologic toxicity.
The Company announced that it was closing its trial in chronic
lymphocytic leukemia in order to focus on other ongoing trials.
Ms. Cahill remarked, "While early responses are not predictive of final
results, we have observed some responses to Cloretazine(R) (VNP40101M) in
relapsed and resistant small cell lung cancer. We are adjusting the dose of
Cloretazine(R) (VNP40101M) on that trial based on toxicities seen to date."
She added, "We made the decision to close the CLL trial at this time in
order to focus our efforts on small cell lung cancer the AML registration
pathway."
Ms. Cahill concluded, "We have both investigator-initiated and Vion-
sponsored studies underway in solid tumors. We look forward to preliminary
data from the small cell lung cancer trial by the end of the year. Also,
given the activity of alkylators in brain tumors and preclinical and
clinical data of Cloretazine(R) (VNP40101M) to date, we will continue our
work with brain tumor specialists to decide on future trials."
Triapine(R)
The Company's second clinical anticancer compound, Triapine(R), is a
potent inhibitor of ribonucleotide reductase, an enzyme necessary for DNA
synthesis and repair. Triapine(R) is being evaluated in several clinical
trials sponsored by the National Cancer Institute (NCI). Since commencement
of the NCI's Triapine(R) program, 13 clinical studies have been conducted
including 5 studies that are ongoing. In addition, up to 5 studies are
currently planned to commence in the coming months, including a study of an
oral formulation and Triapine(R) as a radio-sensitizer.
The Company has decided not to conduct its own study of oral
Triapine(R) at this time, to conserve resources and to focus its efforts on
the registration and life cycle extension of Cloretazine(R) (VNP40101M).
Ms. Cahill noted, "Our Triapine(R) program with the NCI continues. Data
from the first set of trials are expected to be presented this year. We
expect new trials to start shortly, including a trial of oral Triapine(R),
a Phase II trial of Triapine in combination with fludarabine in hematologic
malignancies, and trials of Triapine(R) in combination with radiation. We
continue to search for a registration pathway for Triapine(R), and are
pleased to be working with the NCI in this regard."
VNP40541
The Company plans to file an Investigational New Drug (IND) application
for VNP40541 in June. VNP40541 is a hypoxia-selective compound that
releases the same active agent as Cloretazine(R) (VNP40101M) in hypoxic
(low-oxygen) conditions. Preclinical data on this compound was presented at
the American Association of Cancer Research (AACR) Annual Meetings in 2005
and 2006. A Phase I clinical trial of VNP40541 is planned to commence in
the second half of 2006.
Initial Commercialization Efforts for Cloretazine(R) (VNP40101M)
The Company also reported on its initial efforts to prepare for the
commercialization of Cloretazine(R) (VNP40101M) if and when its pivotal
trials are successfully completed and regulatory approval is obtained.
With respect to validation of the manufacturing process for
Cloretazine(R) (VNP40101M), the Company has completed the manufacturing of
three consecutive lots of active pharmaceutical ingredient (API) and is
working with its contract manufacturer to finalize the related
documentation. Manufacturing lots for validation of the finished product
are planned for this summer.
The Company has completed several additional preclinical studies
necessary for registration, and more studies are underway or scheduled.
In addition, the Company has initiated or completed work related to
market analysis (including targeting, pricing and competitive positioning)
of Cloretazine(R) (VNP40101M) in AML, its initial registration pathway.
Discussions with several contract sales organizations have been conducted
to evaluate requirements for a sales force and product distribution in the
United States.
The Company also announced its plans to meet with the European
Medicines Agency (EMEA) in 2006 to discuss the requirements for
registration of Cloretazine(R) (VNP40101M) in the European Union. The
Company will also hold an Advisory Board Meeting with leading European
leukemia physicians at the Annual Congress of the European Hematology
Association meeting in Amsterdam June 15-18, 2006.
Meghan Fitzgerald, Chief Business Officer, stated, "Even though we are
still in trials and we would not expect a commercial launch prior to 2008,
we are continually evaluating all of our commercialization options for
Cloretazine(R) (VNP40101M) in the United States and the rest of the world,
and will continue to do so as our pivotal trials get closer to completion.
Whether we commercialize Cloretazine(R) (VNP40101M) in the United States,
or choose to partner, we are doing the work necessary to ensure a
successful product launch." She concluded, "Our efforts to find a partner
in the rest-of-the- world are ongoing, and are expected to accelerate as we
establish and meet the requirements for foreign registration."
Vion Pharmaceuticals, Inc. is committed to extending the lives and
improving the quality of life of cancer patients worldwide by developing
and commercializing innovative cancer therapeutics. Vion has two agents in
clinical trials: Cloretazine(R) (VNP40101M), a unique alkylating agent, is
being evaluated in: (i) a Phase III trial in combination with cytarabine in
relapsed acute myelogenous leukemia and (ii) a Phase II pivotal trial as a
single agent in elderly patients with previously untreated de novo
poor-risk acute myelogenous leukemia. Additional trials of Cloretazine(R)
(VNP40101M) as a single agent in adult and pediatric brain tumors, small
cell lung cancer and chronic lymphocytic leukemia, and in combination with
temozolomide in hematologic malignancies, are also underway. Triapine(R), a
potent inhibitor of a key step in DNA synthesis, is being evaluated in
trials sponsored by the National Cancer Institute. In preclinical studies,
Vion is also evaluating VNP40541, a hypoxia-selective compound, and
hydrazone compounds. The Company also is seeking development partners for
TAPET(R), its modified Salmonella vector used to deliver anticancer agents
directly to tumors. For additional information on Vion and its product
development programs, visit the Company's Internet web site at
http://www.vionpharm.com .
This news release contains forward-looking statements. Such statements
are subject to certain risk factors which may cause Vion's plans to differ
or results to vary from those expected, including Vion's ability to secure
external sources of funding to continue its operations, the inability to
access capital and funding on favorable terms, continued operating losses
and the inability to continue operations as a result, its dependence on
regulatory approval for its products, delayed or unfavorable results of
drug trials, the possibility that favorable results of earlier clinical
trials are not predictive of safety and efficacy results in later clinical
trials, the need for additional research and testing, and a variety of
other risks set forth from time to time in Vion's filings with the
Securities and Exchange Commission, including but not limited to the risks
discussed in Vion's Annual Report on Form 10-K for the year ended December
31, 2005. Except in special circumstances in which a duty to update arises
under law when prior disclosure becomes materially misleading in light of
subsequent events, Vion does not intend to update any of these
forward-looking statements to reflect events or circumstances after the
date hereof or to reflect the occurrence of unanticipated events.
Source: Vion Pharmaceuticals
Issuer of this News Release is solely responsible for its
content.
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