Results to be presented at the
52nd American Society of Hematology Annual
Meeting
MISSISSAUGA, ON, Nov. 8 /PRNewswire-FirstCall/ - YM BioSciences
Inc. (NYSE Amex: YMI, TSX: YM), today announced that data from
the initial portion of the Phase I/II trial of its JAK1/JAK2
Inhibitor, CYT387, will be reported in an oral presentation at the
52nd American Society of Hematology (ASH) Annual Meeting to be held
in Orlando, Florida on
December 4-7th, 2010. The
presentation is entitled: "A Phase I/II Study of CYT387, an oral
JAK-1/2 inhibitor, in Myelofibrosis: Significant Response Rates in
Anemia, Splenomegaly, and Constitutional Symptoms". The abstract
describing these results was published online today by ASH and is
also available at YM BioSciences' website
(www.ymbiosciences.com).
"In addition to demonstrating substantial
activity in reducing spleen size and controlling constitutional
symptoms, CYT387 also improved anemia in a considerable number of
patients. This additional benefit could significantly differentiate
our JAK1/JAK2 inhibitor from others in development, which have
reported limited anemia benefit or worsened anemia in some
patients," said Dr. Nick Glover,
President and COO of YM BioSciences. "We look forward to the
presentation of detailed results from this first group of patients
at ASH and anticipate that data from the full Phase II portion of
the study will be available in mid-2011."
The abstract describes results for 36 subjects
enrolled in the 120 patient Phase I/II trial for which recruitment
is ongoing. Of these, 18 patients were from the dose escalation
phase, conducted at Mayo Clinic, Rochester, New York with Dr. Ayalew Tefferi, Professor, Hematology as Study
Chair, and 18 patients were from the subsequent dose confirmation
phase. Twenty subjects (56%) were red cell transfusion-dependent at
study entry. Prior treatment included other JAK inhibitors in ten
patients (nine and one subjects with INCB018424 and TG101348,
respectively) and pomalidomide in nine patients. The median
treatment duration at publication was 15 weeks (range 4-38).
Efficacy Results:
- Anemia Response: The total anemia response rate was 63%. Of 22
subjects who were evaluable for anemia response (baseline Hgb 10
g/dL or red cell transfusion-dependent), nine subjects (41%) had
achieved "Clinical Improvement (CI)" as per the International
Working Group for Myeloproliferative Neoplasms Research and
Treatment (IWG-MRT) criteria, including two of four subjects who
were previously treated with INCB018424. An additional five
subjects experienced a >50% reduction in transfusion
requirement..
- Spleen Size Reduction: Twenty nine (97%) of the 30 evaluable
subjects who had splenomegaly at baseline (median 20 cm; range
10-32 cm) had some degree of spleen size reduction (median 9 cm;
range 2-18 cm). Eleven (37%) patients have achieved a minimum 50%
decrease in palpable spleen size, thus qualifying them for a CI per
IWG-MRT criteria, including three out of eight subjects (38%) who
were previously treated with INCB018424.
- Constitutional symptoms: The proportion of patients with the
following symptoms at baseline were as follows: fatigue (97%),
pruritus (22%), night sweats (38%), cough (13%), bone pain (28%),
and fever (16%). At last follow up, improvement (complete
resolution; CR) in these symptoms was reported by 68% (16% CR), 86%
(57% CR), 83% (75% CR), 75% (50% CR), 78% (44% CR), and 100% (100%
CR), respectively.
Toxicity results:
The abstract reports results for 36 subjects who were evaluable for
toxicity. At the highest dose level (400 mg/day), two of six
subjects experienced dose limiting toxicity (DLT) (one each with
asymptomatic grade three hyperlipasemia and grade three headache
that were reversible upon holding drug); consequently, the maximum
tolerated dose (MTD) was declared at 300 mg/day. In the
dose-confirmation phase, subjects were started at one of two dose
levels that were deemed clinically effective: 150 mg/day (n=15) and
300 mg/day (n=3). Thirty-five subjects were on active therapy at
publication of the abstract: 100 mg/day (n=2), 150 mg/day (n=20),
300 mg/day (n=10), and 400 mg/day (n=3).
CYT387 was well tolerated. No grade 4
non-hematological toxicities were observed. Grade 3 non-hematologic
adverse events were infrequent and included increased transaminases
(n=2), increased alkaline phosphatase (n=2), headache/head pressure
(n=2), increased lipase (n=1), and QTc prolongation (n=1). Thirteen
(36%) subjects experienced "first-dose effect" characterized by
grade 1 lightheadedness and hypotension; this phenomenon was
self-limited and generally resolved within 3-4 hours with rare
recurrence. Grade 3/4 thrombocytopenia was seen in eight (22%)
subjects, and treatment-emergent grade 3 anemia was seen in one
subject only (3%). Treatment-emergent grade 3/4 neutropenia was not
observed.
Oral Presentation at the 52nd American Society
of Hematology Annual Meeting:
An oral presentation of the Phase I/II results from CYT387 will be
delivered on Monday, December 6,
2010 at 11:15 AM in the
Orange County Convention Center,
Valencia B/C as part of the session
named Myeloproliferative Syndromes: Clinical and Translational
Advances in Myeloproliferative Neoplasms. YM will host a conference
call following the presentation to discuss the trial results.
Study Details:
This trial was designed to assess the safety, tolerability, and
pharmacokinetic behavior of CYT387 in a Phase I dose-escalation
study in patients with high- or intermediate-risk primary
myelofibrosis (PMF) and post-PV or post-essential thrombocythemia
(ET) myelofibrosis. The secondary objective was evaluation of
CYT387's benefit to myelofibrosis patients. CYT387 was administered
orally once daily in 28-day cycles. For patients achieving less
than a complete remission after 3 cycles of treatment, escalation
was permitted to the highest tolerated dose in the absence of
disease progression or unacceptable toxicity. Once dose-limiting
toxicity (DLT) was identified, a dose-confirmation cohort initiated
treatment at the maximum tolerated dose (MTD) and/or a lower
clinically effective dose.
For more information on the CYT387 Phase 1/2
trial, go to:
http://clinicaltrials.gov/ct2/show/NCT00935987?term=cyt387&rank=1
About CYT387:
CYT387 is an inhibitor of the kinase enzymes JAK1 and JAK2, which
have been implicated in a family of hematological conditions known
as myeloproliferative neoplasms, including myelofibrosis, and as
well in numerous disorders including indications in hematology,
oncology and inflammatory diseases. Myelofibrosis is a chronic
debilitating disease in which a patient's bone marrow is replaced
by scar tissue and for which treatment options are limited or
unsatisfactory. The U.S. Food and Drug Administration (FDA) has
granted Orphan Drug Designation to CYT387 for the treatment of
myelofibrosis.
YM BioSciences retains the global
commercialization rights to CYT387.
About YM BioSciences
YM BioSciences Inc. is a drug development company advancing three
clinical-stage products: CYT387, a small molecule, dual inhibitor
of JAK1/JAK2 kinase; nimotuzumab, an EGFR-targeting monoclonal
antibody; and CYT997, a potent vascular disrupting agent (VDA).
CYT387 is an orally administered inhibitor of
both the JAK1 and JAK2 kinase enzymes, which have been implicated
in a number of immune cell disorders including myeloproliferative
disorders and inflammatory diseases as well as certain cancers.
CYT387 is currently in a Phase I/II trial in myelofibrosis with
detailed initial safety and activity data expected at the American
Society of Hematology (ASH) meeting in December 2010. Nimotuzumab is a humanized
monoclonal antibody targeting EGFR with an enhanced side effect
profile. Nimotuzumab is being evaluated in numerous Phase II and
III trials worldwide by YM's licensees. CYT997 is an
orally-available small molecule therapeutic with dual mechanisms of
vascular disruption and cytotoxicity, and is currently in a Phase
II trial for glioblastoma multiforme. In addition to YM's three
clinical stage products, the Company has a library of more than
4,000 novel compounds identified through internal research
conducted at YM BioSciences Australia which are currently being
evaluated.
This press release may contain
forward-looking statements, which reflect the Company's current
expectation regarding future events. These forward-looking
statements involve risks and uncertainties that may cause actual
results, events or developments to be materially different from any
future results, events or developments expressed or implied by such
forward-looking statements. Such factors include, but are not
limited to, changing market conditions, the successful and timely
completion of clinical studies, the establishment of corporate
alliances, the impact of competitive products and pricing, new
product development, uncertainties related to the regulatory
approval process and other risks detailed from time to time in the
Company's ongoing quarterly and annual reporting. Certain of the
assumptions made in preparing forward-looking statements include
but are not limited to the following: that nimotuzumab will
continue to demonstrate a competitive safety profile in ongoing and
future clinical trials; that our JAK1/JAK2 inhibitor CYT387 and our
VDA small molecule CYT997 will generate positive efficacy and
safety data in future clinical trials; that YM and its various
partners will complete their respective clinical trials within the
timelines communicated in this release. Except as required by
applicable securities laws, we undertake no obligation to
publicly update or revise any forward-looking statements, whether
as a result of new information, future events or otherwise.
SOURCE YM BioSciences Inc.
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