Onconova Therapeutics, Inc. (NASDAQ:ONTX), 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), has announced
data demonstrating responses of oral rigosertib with azacitidine in
Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS),
as well as oral rigosertib as a single agent. The findings were
presented by Onconova, Mount Sinai, and SymBio at the 22nd Congress
of the European Hematology Association taking place on June 22-24
in Madrid, Spain.
“Advancing oral rigosertib in the clinic as a stand-alone agent,
and providing further evidence for activity of rigosertib in
combination with azacitidine in patients with MDS and AML
represents an extension of our pipeline,” said Dr. Ramesh Kumar,
CEO of Onconova. “We are positioned for multiple key milestones in
2017 and beyond, beginning with the interim analysis of our pivotal
Phase 3 INSPIRE trial later this year.”
Full copies of the posters and oral presentations can be
accessed by visiting “Scientific Presentations” in the Investors
section of Onconova’s website.
Oral Presentation: Oral Rigosertib Combined with
Azacitidine in Patients with AML and MDS; Effects in Treatment
Naive and Relapsed/Refractory Patients
A novel combination therapy of oral rigosertib plus injectable
azacitidine was tested in this trial (09-08) at three sites in the
U.S. and Europe, representing a first-in-man study of this
approach. Eight AML patients were evaluable for response, with an
overall response rate (ORR) of 37.5%, and responses in both
secondary and refractory AML. Two additional patients had stable
disease (25%). Responses were durable, with the longest response in
AML approaching one year.
Among 33 evaluable MDS patients, ORR was 76%. Complete remission
(CR) in eight (24%), concurrent marrow CR (mCR) and hematologic
improvement (HI) in 10 (30%), mCR alone in six (18%), and HI alone
in 1 (3%). ORR was 85% in hypomethylating agent (HMA) naïve
patients and 62% in HMA resistant patients.
Earlier, Phase 1 and Phase 2 data in first and second-line
higher risk (HR)-MDS patients were presented at the 2016 American
Society of Hematology (ASH) Meeting and updated at the 2017 ASH and
MDS Foundation meetings. Based on these results, the authors
determined that continued study in AML is warranted.
A Phase 3 study of the combination of oral rigosertib and
azacitidine in patients with treatment naïve HR-MDS is currently
being designed based on an end-of-phase 2 meeting with the Food and
Drug Administration.
E-Poster: Rigosertib Combined with Azacitidine
Epigenetically Modulates Chromatin and Hematopoietic Stem Cell
Populations in MDS
Onconova’s collaborators from the Mount Sinai School of Medicine
investigated the in vitro effects of rigosertib combined with
azacitidine or vorinostat on two cell lines and on bone marrow
samples from patients treated in the Phase 1-2 study, obtained
prior to and after one cycle of the combination regimen.
Azacitidine is an HMA and vorinostat is an inhibitor of Histone
Deacetylase. Rigosertib’s mechanism of action is reported to be
mediated by binding to a Ras Binding Domain present in Ras and its
effector proteins, including PI3 Kinase and Raf. Chromatin
remodeling by changes in methylation and acetylation were noted in
cell-lines treated with all three agents, as well as after
treatment with the two combinations. The nature of the changes
induced with the two combinations was distinct.
The authors propose that rigosertib potentially functions as a
chromatin modifying agent in combination with azacitidine and may
overcome HMA resistance through chromatin remodeling. Rigosertib
alone, and in combination, also leads to epigenetic reprogramming
of hematopoietic stem cell populations (HSPCs) that may manifest in
hematological improvements in the clinical setting. A U.S. patent
describing the synergistic activity of rigosertib in combination
with azacitidine has been issued.
SymBio, Onconova’s Partner in Japan and Korea, Presents
Phase 1 data Demonstrating Oral Rigosertib as a Single
Agent
E-Poster: A Multicenter, Open-label, Phase 1 Clinical
Study; Safety, Efficacy, and Pharmacokinetics of Oral Rigosertib in
Japanese Patients with Recurrent/Relapsed or Refractory
MDS
A multicenter, open-label, Phase 1 clinical
study of oral rigosertib (primary endpoint was dose-limiting
toxicity) indicated that the recommended dose for a Phase 2
clinical study is 560 mg BID in a 2-out-of-3-week administration
scheme in Japanese patients with recurrent/relapsed or refractory
MDS. This regimen of oral rigosertib was well tolerated.
The primary endpoint of the study was
dose-limiting toxicity. The secondary endpoints were 1) safety as
assessed by adverse events and laboratory results, 2) efficacy as
defined by the International Working Group 2006 Criteria, and 3)
pharmacokinetics. Both hematological remission rate and
hematological improvement rate were 11.1% of the nine patients with
a median age of 70. In this study, the recommended dose was 560 mg
BID. This study and a companion Phase 1 study with IV rigosertib
were designed to obtain pharmacokinetics, safety, tolerability and
efficacy data in MDS patients in Japan. Currently, SymBio is
enrolling patients in a pivotal Phase 3 INSPIRE global study to
assess the safety and efficacy of IV rigosertib.
Publication: Safety, Efficacy and
Pharmacokinetics of Intravenous Rigosertib in Japanese Patients
with Recurrent/Relapsed or Refractory MDS; A Multicenter,
Open-label, Phase 1 Study
A multicenter, open-label, Phase 1 study of
intravenous rigosertib was conducted to evaluate its safety,
efficacy, and pharmacokinetics and to determine the recommended
dose (RD) for Japanese patients.
The Phase 1 study showed that intravenous
rigosertib (1,800 mg daily) for consecutive 72 hours was
well-tolerated, indicating that this is the RD for Japanese
patients with MDS, similar to a Phase 3 study in the U.S. Based on
these clinical outcomes, Japanese patients with MDS are
participating in a global randomized Phase 3 study to compare
rigosertib with physicians’ choice of treatment.
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 we
believe 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,
while causing minimal damage to normal cells. Onconova has three
product candidates in the clinical stage and several pre-clinical
programs. Advanced clinical trials with the Company’s lead
compound, rigosertib, are 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 Rigosertib
The 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 MDS, after failure of
hypomethylating agent, or HMA, therapy. This formulation is
intended for patients with advanced disease, provides long
duration of exposure, and ensures dosing under a controlled
setting.
About INSPIRE
The INternational Study of
Phase III IV
RigosErtib, or INSPIRE, is based
on guidance received from the U.S. Food and Drug Administration and
European Medicines Agency and derives from the findings of the
ONTIME Phase 3 trial. 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 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 Rigosertib
The 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 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 Statements
Some 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 CONTACT:
http://www.onconova.com/contact/
INVESTOR RELATIONS CONTACT:
Lisa Sher, MBS Value Partners on behalf of Onconova Therapeutics
Lisa.Sher@mbsvalue.com / (212) 750-5800
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