YM BioSciences Reports Updated Phase I/II Data for its JAK1/JAK2 Inhibitor CYT387 at ASH 2011
- Significant and durable responses in anemia, splenomegaly and
constitutional symptoms reported -
- Well tolerated for dosing periods up to and exceeding two years -
- MRI results confirm meaningful improvements in splenomegaly -
MISSISSAUGA, ON, Dec. 12, 2011 /PRNewswire/ – YM BioSciences Inc. (NYSE Amex: YMI, TSX: YM), today reported updated results from the ongoing Phase I/II study of
its JAK1/JAK2 inhibitor, CYT387, for the treatment of myelofibrosis.
The results are being presented this evening in a poster session at the
53rd Annual Meeting of the American Society of Hematology underway in
San Diego, CA.
“In this multicenter study, CYT387 continues to demonstrate a unique
ability to render and maintain myelofibrosis patients transfusion
independent for clinically-relevant periods, while also producing
significant and durable improvements in their splenomegaly and
constitutional symptoms,” said Dr. Nick Glover, President and CEO of YM
BioSciences. “In addition, MRI results obtained from a subset of
subjects confirm the meaningful improvements in splenomegaly as
measured by palpation. Moreover, CYT387 was well tolerated, with dosing
up to and exceeding two years.”
“While additional assessments and analyses are ongoing across dose
levels, 300 mg/day appears to be a safe and effective dosing regimen
that warrants further clinical development,” added Dr. Glover. “We look
forward to leveraging these data to advance our regulatory strategy and
our business development activities with the goal of starting pivotal
trials in mid-2012.”
Phase I/II Study Updated Results
The Core Phase I/II study has completed enrollment of 166 myelofibrosis
patients across six study sites. The Core study consists of nine 28-day
treatment cycles where CYT387 is orally self-administered, primarily at
dosages of 150 mg once-daily (QD), 300 mg QD or 150 mg twice-daily
(BID). Patients who tolerate and benefit from the drug may continue to
receive CYT387 beyond the Core study in an Extension phase. While data
collection and analysis are ongoing, preliminary safety and efficacy
results from this multicenter study are presented below.
The majority of the 166 patients enrolled have Primary Myelofibrosis
(65%); 22% have Post-Polycythemia vera and 14% have Post-Essential
thrombocythemia. Other patient characteristics include:
-- DIPSS-Plus category: Int-1 - 11%; Int-2 - 61%; High - 28% -- JAK2V617F positive: 76% -- Red blood cell transfusion-dependent: 44% -- Palpable splenomegaly >10 cm: 80%
The trial also enrolled patients who had received previous therapies,
including other JAK inhibitors (12%) and IMiDs (9%).
The median follow-up time for patients in the Core study and Extension
phase is 10.4 months (range: 0.8-25.6 months; ongoing). To date, 97% of
patients who have completed the Core study have continued into the
Extension phase. During the Core study, 32 patients (19%) have
discontinued the study, five for possibly or probably related adverse
events, for a current overall retention rate of 81%. The retention rate
during the Extension phase is currently 79%.
Of the 68 patients who were transfusion dependent at baseline, to date
54% have become transfusion independent for a minimum of 12 weeks. The
median duration of the transfusion-free period has not yet been reached
(range: 82-506 days, ongoing). More than 25% of subjects who were not
receiving transfusions while on study experienced at least a 1 g/dL
increase in hemoglobin lasting for more than eight weeks.
Of the 26 patients who were dosed at 300mg QD and were transfusion
dependent at baseline, to date 65% have become transfusion independent
for a minimum of 12 weeks.
Of the 142 patients evaluable for spleen response, 31% achieved a
response per IWG-MRT*. The median duration of spleen response has not
yet been reached (range: 55 – 574 days, ongoing). The median time to
spleen response was 15 days (range: 6 – 260 days, ongoing). To date,
49% of patients achieved more than a 50% maximal decrease in spleen
size from baseline, with 87% achieving more than a 25% maximal
Of the 51 patients who were dosed at 300mg QD and were evaluable for
spleen response, 33% achieved a response per IWG-MRT.
Eleven patients were evaluable for spleen response both by MRI and by
palpation. The response rate was 64% by MRI (defined as a 35% decrease
in spleen volume) and 45% by palpation (defined as a 50% decrease in
spleen length). The median splenic decrease from baseline at three
months was -41% by volume measured by MRI and -45% by length measured
*International Working Group for Myelofibrosis Research and Treatment
Constitutional Symptoms Response
The majority of patients reporting constitutional symptoms at baseline
demonstrated a Complete Resolution or Marked Improvement of their
symptoms, including night sweats, pruritus and bone pain.
CYT387 is well tolerated in myelofibrosis patients for dosing periods up
to and exceeding two years. Reported adverse effects include
thrombocytopenia; transient, mild dizziness; mild peripheral
neuropathy; and abnormalities in liver/pancreas-related laboratory
tests. Treatment emergent anemia and neutropenia were rarely reported.
Poster presentation and YM conference call:
The updated results from the Phase I/II study will be presented in a
poster session at the 53rd Annual Meeting of the American Society of
Hematology. Poster #3849, entitled “Safety and Efficacy of CYT387, a
JAK1 and JAK2 Inhibitor for the Treatment of Myelofibrosis”, will be
presented at Session #634, Myeloproliferative Syndromes: Poster III,
being held on Monday, December 12th from 6:00-8:00pm PT in Hall GH of
the San Diego Convention Center.
YM will also host a webcast meeting open to members of the investment
community to discuss these results. This event will be held from
6:30-7:30am PT on Tuesday, December 13th in the Grand Ballroom of the
Hotel Palomar, 1047 Fifth Avenue, San Diego. Access to the webcast will
be available from YM’s website at www.ymbiosciences.com or at www.newswire.ca. The event can also be heard by dialing in to (647) 427-7450 or
toll-free at (888) 231-8191.
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 other 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.
Both the U.S. Food and Drug Administration (FDA) and the European
Commission have designated CYT387 an Orphan Drug for the treatment of
YM BioSciences retains full global commercialization rights to CYT387.
About YM BioSciences
YM BioSciences Inc. is a drug development company advancing three
products: CYT387, a small molecule, dual inhibitor of the JAK1/JAK2
kinases; nimotuzumab, an EGFR-targeting monoclonal antibody; and
CYT997, a vascular disrupting agent (VDA).
CYT387 is an orally administered inhibitor of both the JAK1 and JAK2
kinases, which have been implicated in a number of immune cell
disorders including myeloproliferative neoplasms and inflammatory
diseases as well as certain cancers. CYT387 is currently in a 166
patient Phase I/II trial in myelofibrosis that has completed
enrollment, as well as a 60 patient Phase II BID trial that is
recruiting patients. Nimotuzumab is a humanized monoclonal antibody
targeting EGFR with an enhanced side-effect profile over currently
marketed EGFR-targeting antibodies. Nimotuzumab is being evaluated in
numerous Phase II and III trials worldwide. CYT997 is an
orally-available small molecule therapeutic with dual mechanisms of
vascular disruption and cytotoxicity, and has completed a Phase II
trial in glioblastoma multiforme. In addition to YM’s three products,
the Company has several preclinical research programs underway with
candidates from its library of novel compounds identified through
internal research conducted at YM BioSciences Australia.
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
or the ability to obtain drug product in sufficient quantity or at
standards acceptable to health regulatory authorities to complete
clinical trials or to meet commercial demand; 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 CYT387,
nimotuzumab and CYT997 will generate positive efficacy and safety data
in ongoing and future clinical trials, and that YM and its various
licensees will complete their respective clinical trials and disclose
data 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.