-- Plans to File "Fast Track" BLA --
WALTHAM, Mass., Jan. 24 /PRNewswire-FirstCall/--
AltaRex Corp. (AXO.TO, ALXFF.OTC) today announced positive clinical results
from a primary analysis of its 345-patient OvaRex(R) combined U.S. and
Canadian phase IIb trial in metastatic late stage ovarian cancer. Based on
these results, the Company is updating its plans to complete the OvaRex(R)
development program. Highlights are as follows:
(Photo: http://www.newscom.com/cgi-bin/prnh/20000831/ALTREXLOGO )
-- The phase IIb trial primary analysis demonstrates statistically
favorable results for a well-defined population in the U.S. study,
while non-significant in Canada with further analysis still ongoing.
The Company believes that the results, when combined with two other
well-controlled U.S. trials and two open trials, will provide the basis
for the filing of a "Fast Track" Biologics License Application (BLA)
with the U.S. Food and Drug Administration (FDA).
-- An amendment to the Company's Investigational New Drug submission has
been filed with the FDA to conduct a pharmacokinetic study to establish
the comparability of OvaRex(R) used in the clinical trials and the new
cell culture-based product. This 24-patient trial is planned to be
completed in the second quarter of this year.
-- Two additional U.S. trials will also be reported in the second quarter
and are expected to support the findings in the well-defined patient
population in the phase IIb trial.
-- The Company is also pursuing options for its manufacturing program, now
delayed, to ensure the timely completion of remaining steps required
for the BLA and to reduce cash requirements, as the Company's plans are
based on raising additional capital.
-- With these accomplishments, the BLA filing would commence on a rolling
basis in the third quarter of this year.
The phase IIb trial compared time to disease relapse (TTR) of OvaRex(R)
monotherapy with placebo following primary therapy (surgery and chemotherapy).
There is no drug approved for this stage of disease and placebo-controlled
trials of this type have not been previously conducted. Historically, this
study started as two separate phase II trials, one in Canada with patient
enrollment beginning in 1997, and a second in the U.S. starting in 1998. The
Company combined these separate trials into a single phase II/III study (i.e.
phase IIb) with the power to detect a 40% difference in median TTR between all
active and placebo patients, the defined primary endpoint. As the primary
endpoint was not met in the previously reported interim analysis (252 of the
345 patients) and now in the primary analysis, the Company's U.S. registration
plan has been and remains predicated on submitting results from multiple well-
controlled phase II trials for "Fast Track" review and "Accelerated Approval",
which is a typical route for approval of drugs or biologics in cancer. For
the primary analysis, an Endpoint Monitoring Board (EMB) evaluated individual
investigator determinations of TTR, and EMB determinations of TTR are
reported.
For a well-defined population accounting for roughly 33% (N=111) of the
treated patients (N=342), which is characterized by a sufficient level of
tumor antigen CA125 in the blood and having received at least four doses,
OvaRex(R) provides evidence of an overall positive treatment effect. In the
U.S. study, the median TTR for OvaRex(R) is statistically significant (15.5
months vs. 8.5 months, p=.05). However, in the Canadian study, the result is
non-significant (8.2 months vs. 10.3 months for placebo). In this same well-
defined population, an analysis of relapse-free survival (at 12 months from
initiation of treatment) favors OvaRex(R) on an overall basis (46% vs. 30%,
p=.082). The U.S. study result in this case is highly statistically
significant (57% vs. 19%, p=.006), while the result in the Canadian study is
non-significant (33% vs. 39% for placebo).
With regard to the defined primary endpoint, the overall median TTR for
OvaRex(R) as compared with placebo was not statistically significant, with
substantially different results in the U.S. and Canadian studies. The median
TTR for OvaRex(R) (N=73) in the U.S. was 13.3 months as compared to 10.3
months (+29%) with placebo (N=72). In Canada, the median TTR for OvaRex(R)
(N=97) was 7.5 months as compared to 10.3 months (-27%) for placebo (N=100).
Importantly, as indicated by the safety, quality of life and immunological
response data, the Company believes that OvaRex(R) treatment was not
deleterious in the Canadian group and that the drug was not inactive.
Preliminary findings suggest that the Canadian OvaRex(R) population included
many patients with poor risk factors for early relapse, including malignant
ascites, residual disease following surgery, and high levels of tumor antigen
after the initiation of primary chemotherapy. This preliminary analysis
suggests that randomization to OvaRex(R) and placebo in the Canadian study was
not optimally balanced for these prognostic risk factors that can influence
disease outcomes and analyses. As a full data set is only recently available
to the Company, additional analyses are ongoing to determine further
population differences not yet identified.
Among all OvaRex(R) treated patients (N=172) and comparing immune
responders to non-responders, median TTR was highly statistically significant
overall (p<.0001, 13.4 months vs. 4.7 months), and in the U.S. (p<.0027) and
Canadian (p<.0001) studies. These immune responder results are consistent
with the previously reported well-controlled trial (N=55) conducted in the
U.S. in watchful waiting patients where there was also a highly statistically
significant difference for the immune responders (p=.0129), a defined primary
endpoint for the trial.
The Company has ongoing a third U.S. well-controlled trial (N=102) in the
same population as the phase IIb trial, comparing TTR for immune responders
vs. non-responders using three dosage regimens. The Company expects to report
on this trial as well as an open trial in recurrent disease (N=20) in the
second quarter. The Company has now filed a regulatory amendment in the U.S.
to support the conduct of the FDA agreed-upon pharmacokinetics (PK) trial to
establish the comparability of OvaRex(R) used in the clinical trials and the
new cell culture-based product, also planned to be completed for analysis in
the second quarter of this year.
The BLA is expected to initiate on a rolling basis with the clinical and
PK data in the third quarter, roughly a six month delay from the previously
anticipated timeline. The filing will include over 335 patients having
received OvaRex(R) in three well-controlled trials, two open trials and a PK
study, as well as an additional 200 patients treated with OvaRex(R) in Germany
and evaluated retrospectively.
In every trial, OvaRex(R) treatment demonstrated a benign safety profile
(similar to placebo, when compared). In this phase IIb trial, the number of
drug discontinuances for adverse events was four for both OvaRex(R) (2.3%) and
placebo (2.4%), there were no anaphylactic reactions and patients were not
prevented from receiving multiple doses (as many as 11) of this murine
antibody. Also, the safety profile was further supported with preservation of
quality of life equivalent to placebo when measured by a validated patient
questionnaire.
Richard Bagley, President and CEO of AltaRex, commented, "While we would
have preferred unequivocal evidence of efficacy on an overall intent to treat
basis, we believe we have a clear route to file a BLA under "Fast Track" and
"Accelerated Approval" provisions where one must demonstrate a meaningful
benefit in a well-defined population with an unmet medical need. Late stage
ovarian cancer is like most other metastatic solid tumors where a treatment
benefit is generally measured in weeks and months, with the major exception
that most ovarian cancer patients have metastatic disease on diagnosis and
available treatments can be toxic and can negatively impact quality of life.
To prolong time to disease relapse in a defined population - without
deleterious effects and diminution of quality of life - certainly addresses an
unmet medical need."
"We will present overall conclusions of our studies to the Society for
Gynecologic Oncology annual meeting in March and the American Association for
Cancer Research annual meeting in a minisymposium in April, and have submitted
abstracts to present at the American Society of Clinical Oncology annual
meeting in May."
About OvaRex(R) MAb
OvaRex(R) MAb (oregovomab) is a fully foreign monoclonal antibody that
targets an ovarian cancer-associated antigen CA125 in circulation, and is
designed to induce broad and robust immune responses against CA125 and result
in extended relapse-free or progression-free survival without a deleterious
effect on safety and quality of life.
About Ovarian Cancer -The Disease That Whispers
Ovarian cancer is the most serious form of gynecologic cancer, affecting
one of every 55 women, and killing 40 women in the United States every day.
Ovarian cancer is referred to as the "Disease that Whispers" because vague
symptoms and the difficult location of the ovaries lead to 75% of diagnoses
being made late, when the disease has reached an advanced metastatic stage.
While first-line treatment of surgery and chemotherapy usually results in
temporary remission, recurrence of advanced stage disease is almost inevitable
and the 5-year survival rate remains at less than 20%.
This news release contains forward-looking statements that involve risks
and uncertainties, which may cause actual results to differ materially from
the statements made. For this purpose, any statements that are contained
herein that are not statements of historical fact may be deemed to be forward-
looking statements. Without limiting the foregoing, the words "believes,"
"anticipates," "plans," "intends," "expects" and similar expressions are
intended to identify forward-looking statements. Such risks and uncertainties
include, but are not limited to, our need for capital and the risk that the
Company can not raise funds on a timely basis on satisfactory terms or at all,
changing market conditions, uncertainties regarding the timely and successful
completion of clinical trials such as the PK trial, the dosing trial and the
open trial referred to in this release, patient enrollment rates, uncertainty
of preclinical, retrospective, early and interim clinical trial results, which
may not be indicative of results that will be obtained in ongoing or future
clinical trials or additional analyses of completed clinical trials, whether
the Company will file for regulatory approval on a timely basis, uncertainties
as to when, if at all, the FDA will accept or approve the Company's regulatory
filings for its products, the need to establish and scale-up manufacturing
processes, the need to obtain and maintain corporate alliances, uncertainty as
to the timely development and market acceptance of the Company's products,
uncertainty as to whether patents will issue from pending patent applications
and, if issued, as to whether such patents will be sufficiently broad to
protect the Company's technology, and other risks detailed from time-to-time
in the Company's filings with the United States Securities and Exchange
Commission and Canadian securities authorities. The Company does not assume
any obligation to update any forward-looking statement.
THE TORONTO STOCK EXCHANGE HAS NOT APPROVED OR DISAPPROVED OF THE
INFORMATION CONTAINED HEREIN
SOURCE AltaRex Corp.
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http://www.altarex.com
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CONTACT:
Peter Gonze, Senior Vice President,
Operations and Investor Relations, +1-781-672-0138, ext. 1503,
pgonze@altarex.com, or Sondra Henrichon, Director, Investor
Relations and Corp. Communications, +1-781-672-0138, ext. 1510,
shenrichon@altarex.com, both of AltaRex Corp.
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