Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3
clinical-stage biopharmaceutical company focused on discovering and
developing novel products to treat cancer, delivered two poster
presentations highlighting drug activity and the mechanism of
action of rigosertib in Myelodysplastic Syndromes during the 59th
American Society of Hematology (ASH) Annual Meeting and
Exposition in Atlanta. Rigosertib, the Company’s lead
compound, is being evaluated in Phase 3 and Phase 2 clinical trials
in both intravenous and oral forms, respectively.
Rigosertib Oral is Active as a Single
Agent in Lower-risk Transfusion Dependent MDS
Title: Rigosertib Oral in
Transfusion Dependent Lower-Risk Myelodysplastic Syndromes
(LR-MDS): Optimization of Dose and Rate of Transfusion Independence
(TI) or Transfusion Reduction (TR) in a Single-Arm Phase 2
Study
Eighty-two patients with a median age of 70
years (range 54-90) were enrolled at 5 clinical sites, and received
a median of 5.4 months (range 0.1-28.8) of oral rigosertib. Of the
82 enrolled patients, 9 patients were treated with 560 mg BID
continuously, 7 patients were treated with 560 mg in the AM and 280
mg in the PM continuously, 35 patients were treated with 560mg BID
intermittently (as defined as 2 out of 3 weeks), and 31 patients
were treated with 560mg in the AM and 280mg in the PM
intermittently. Sixty patients were treated with ESA and oral
rigosertib during the study.
Of the 82 patients, 66 patients received
intermittent dosing for at least 8 consecutive weeks; and 20 of 62
evaluable patients (32%) achieved TI lasting 8 to 85+ weeks; with a
median of 18 weeks. The highest rate of TI (44%) was observed in
the 560 mg BID intermittent cohort: 15 of 34 eligible patients
achieved TI lasting 8 to 85+ weeks; with a median of 18 weeks.
Ninety-three percent (93%) of these 15 patients received rigosertib
with continued ESA.
The safety assessable population (n = 82)
received at least 1 week of rigosertib treatment. Notably, no
significant treatment emergent myelosuppression, or other notable
adverse events (AEs), were evident in these patients. Continuous
rigosertib dosing cohorts were closed early due to higher urinary
AEs. For all intermittent patients (n=66), the most frequent
treatment emergent AEs observed were urinary with pollakiuria
(42.4%), fatigue and micturition urgency (33.3%), urinary tract
pain (28.8%), hematuria and dysuria (24.2%). Intermittent and
reduced dosing of rigosertib (560 mg AM, 280 mg PM during 14 days
of 21-day cycles) was associated with a significantly reduced
incidence of urinary toxicity. All AEs were reversible once
rigosertib dosing was reduced or discontinued. Strategies to
ameliorate or manage the urinary AEs are under investigation.
In conclusion, oral rigosertib treatment
resulted in high rates of transfusion reduction and TI. Patients
administered rigosertib for 2 out of 3 weeks at a dose of 560 mg
BID (1120 mg over 24 hours) achieved an impressive TI rate of 44%
(15/34). Based on the rate of TI, and the observed urinary AEs, the
risk benefit profile of oral intermittent dosing is favorable. Oral
rigosertib at a total dose of 1120 mg over 24 hours administered
intermittently in HR-MDS patients in combination with azacitidine
is now being studied, with further exploration to optimize dose and
mitigate urinary AEs.
Dr. Azra Raza, lead investigator of the study,
commented, “This collaborative study originated at our clinic in
Columbia and spanned several years of treatment and follow-up of
transfusion dependent lower-risk MDS patients treated with oral
rigosertib. The very high response rate reported is remarkable, as
is the noted durable benefit to patients who are burdened by the
need for frequent transfusions. Since these patients have few FDA
approved therapeutic options, we are excited about expanding these
studies to pivotal trials. The tolerability and convenience of
administration of oral rigosertib will be key determinants of
success in future studies.”
This poster presentation was delivered by lead
co-author Aref Al-Kali, MD, Division of Hematology, Mayo Clinic,
Rochester, MN on Saturday, December 9, 2017. The reported results
updated a study lead by Azra Raza, MD, Department of Medicine,
Columbia University Medical Center, New York, NY.
A copy of the presentation is available by
visiting the Scientific Presentations section of Onconova’s
website.
Mechanistic Rationale of Combination
Therapy with Rigosertib
Title: Effects of Rigosertib
(RIGO) Alone or in Combination with Azacitidine or Vorinostat on
Epigenetic Reprogramming of CD34+ Cells in the Myelodysplastic
Syndrome
This presentation reported the findings of
rigosertib alone or in combination with azacitidine or vorinostat
on epigenetic reprogramming or molecular changes of CD34+ cells in
MDS. The study results indicate that epigenetic effects of
rigosertib on chromatin alterations may lead to improved
hematopoietic function and response in the clinical setting, and
expanded the understanding of the mechanism of action of rigosertib
in combination with azacitidine. These preclinical models suggest
potential novel clinical strategies with rigosertib and azacitidine
to improve outcomes for patients with higher-risk MDS. Oral
rigosertib in combination with azacitidine is now being studied in
higher-risk MDS patients.
Dr. Lewis Silverman, the lead investigator of
the study, commented, “A large body of evidence with both
intravenous and oral rigosertib supports the activity of this novel
agent in MDS patients. Based on our laboratory studies and a US
patent, a combination regimen of oral rigosertib with azacitidine
has been explored in Phase 2 trials and the promising results of
these trials are providing the basis for the design of a pivotal
Phase 3 study. Our research continues to explore the
mechanistic basis of the impressive and durable responses noted in
higher-risk MDS patients at Mount Sinai and other collaborating
institutions. Such understanding may permit design of other
combinations, as well as biomarkers for patient selection and
theranostic uses in the near future.”
This poster presentation was delivered by lead
author Lewis R Silverman, MD, Tisch Cancer Institute, Icahn School
of Medicine, New York, NY on Monday, December 11, 2017.
A copy of the presentation is available by
visiting the Scientific Presentations section of Onconova’s
website.
About Onconova Therapeutics, Inc.Onconova
Therapeutics, Inc. is a Phase 3-stage biopharmaceutical company
focused on discovering and developing novel small molecule drug
candidates to treat cancer, with a primary focus on Myelodysplastic
Syndromes (MDS). Rigosertib, Onconova's lead candidate, is a
proprietary Phase 3 small molecule agent, which the Company
believes blocks cellular signaling by targeting RAS effector
pathways. Using a proprietary chemistry platform, Onconova
has created a pipeline of targeted agents designed to work against
specific cellular pathways that are important in cancer cells.
Onconova has three product candidates in the clinical stage and
several pre-clinical programs. The advanced clinical trial with the
Company’s lead compound, rigosertib, is aimed at what the
Company believes are unmet medical needs of patients with MDS. For
more information, please visit http://www.onconova.com.
About IV RigosertibThe intravenous form of
rigosertib has been employed in Phase 1, 2, and 3 clinical trials
involving more than 800 patients, and is currently being evaluated
in the randomized Phase 3 international INSPIRE trial for patients
with higher-risk (HR) MDS, after failure of hypomethylating agent,
or HMA, therapy.
About
INSPIREThe INternational Study
of Phase
III IV RigosErtib,
or INSPIRE, trial design was finalized following guidance received
from the U.S. Food and Drug Administration and European
Medicines Agency. INSPIRE is a multi-center, randomized
controlled study to assess the efficacy and safety of IV rigosertib
in HR-MDS patients who had progressed on, failed to respond to, or
relapsed after previous treatment with an HMA within the first 9
months or nine cycles over the course of one year after initiation
of HMA treatment. This time frame optimizes the opportunity
to respond to treatment with an HMA prior to declaring treatment
failure, as per the National Comprehensive Cancer Network (NCCN)
Guidelines. The trial will enroll approximately 225 patients
randomized at a 2:1 ratio into two treatment arms: IV rigosertib
plus Best Supportive Care versus Physician's Choice plus Best
Supportive Care. The primary endpoint of INSPIRE is overall
survival and an interim analysis is anticipated. Full details of
the INSPIRE trial, such as inclusion and exclusion criteria, as
well as secondary endpoints, can be found on clinicaltrials.gov
(NCT02562443).
About Oral RigosertibThe oral
form of rigosertib was developed to provide more convenient dosing
for use where the duration of treatment may extend to multiple
years. This dosage form also supports many combination therapy
modalities. To date, 368 patients have been treated with the oral
formulation of rigosertib. Initial studies with single-agent
oral rigosertib were conducted in hematological malignancies,
lower-risk MDS, and solid tumors. Combination therapy of oral
rigosertib with azacitidine and chemoradiotherapy has also been
explored. Currently, oral rigosertib is being developed as a
combination therapy together with azacitidine for patients with
higher-risk MDS who require HMA therapy. A Phase 1/2 trial of
the combination therapy has been fully enrolled and the preliminary
results were presented in 2016. This novel combination is the
subject of an issued US patent with earliest expiration in
2028.
Forward Looking StatementsSome
of the statements in this release are forward-looking statements
within the meaning of Section 27A of the Securities Act of 1933, as
amended, Section 21E of the Securities Exchange Act of 1934, as
amended, and the Private Securities Litigation Reform Act of 1995,
and involve risks and uncertainties. These statements relate to
future events or Onconova Therapeutics, Inc.'s future operations,
clinical development of Onconova's product candidates and
presentation of data with respect thereto, regulatory approvals,
expectations regarding the sufficiency of Onconova's cash and other
resources to fund operating expenses and capital expenditures,
Onconova's anticipated milestones and future expectations and plans
and prospects. Although Onconova believes that the expectations
reflected in such forward-looking statements are reasonable as of
the date made, expectations may prove to have been materially
different from the results expressed or implied by such
forward-looking statements. Onconova has attempted to identify
forward-looking statements by terminology including "believes,"
"estimates," "anticipates," "expects," "plans," "intends," "may,"
"could," "might," "will," "should," "approximately" or other words
that convey uncertainty of future events or outcomes. These
statements are only predictions and involve known and unknown
risks, uncertainties, and other factors, including Onconova's
ability to continue as a going concern, the need for additional
financing and current plans and future needs to scale back
operations if adequate financing is not obtained, the success and
timing of Onconova's clinical trials and regulatory approval of
protocols, and those discussed under the heading "Risk Factors" in
Onconova's most recent Annual Report on Form 10-K and quarterly
reports on Form 10-Q.
Any forward-looking statements contained in this
release speak only as of its date. Onconova undertakes no
obligation to update any forward-looking statements contained in
this release to reflect events or circumstances occurring after its
date or to reflect the occurrence of unanticipated events.
General
Contacthttp://www.onconova.com/contact/
Investor Relations ContactKatja
Buhrer, Affinity Growth Advisors on behalf
of Onconova TherapeuticsKatja.buhrer@affinitygrowth.com /
(212) 661-7004Source: Onconova Therapeutics, Inc.
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