Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3
clinical-stage biopharmaceutical company focused on discovering and
developing novel products to treat cancer, announces the
presentation of the efficacy and safety results of oral rigosertib
in combination with azacitidine (Vidaza®) in patients with HR-MDS
reported at an oral presentation during the 60th American Society
of Hematology (ASH) Annual Meeting and Exposition in San
Diego. Rigosertib, the Company’s lead compound, is being evaluated
in both intravenous and oral forms.
ORAL PRESENTATION:
Phase 2 Expansion Study of Oral
Rigosertib Combined with Azacitidine treatment in Patients with
Higher-Risk (HR) Myelodysplastic Syndromes (MDS): Efficacy and
Safety Results in HMA Treatment Naïve & Relapsed
(Rel)/Refractory (Ref) Patients
Session Name: 637.
Myelodysplastic Syndromes – Clinical Studies: Novel Therapeutics I
Date: Saturday, December 1, 2018
Presentation Time: 4:15 PM PST Seventy-four (74)
patients were treated with a median age of 69 years (range 42-90)
at 9 clinical sites, and received either 840 mg or 1,120 mg of oral
rigosertib daily divided into two doses, in combination with a
standard dose of injectable azacitidine. Of the 55 evaluable
patients, 29 patients were treated with a daily dose of 1,120 mg of
oral rigosertib, either 560 mg twice daily (12 patients) or 840 mg
in the a.m. and 280 mg in the afternoon (17 patients). Twenty-six
patients were treated with 560 mg in the AM and 280 mg in the PM
(daily dose of 840 mg) for the first three weeks of a four-week
cycle. All patients also received 75 mg/m2/day SC or IV azacitidine
during the second week of the four-week cycle. The median duration
of treatment for the HMA naïve and HMA failed patients was 7.8 and
4.9 months respectively. The median duration of response in these
groups was 12.2 and 10.8 months, respectively.
The overall response rate (ORR) using the IWG
2006 criteria, in 29 HMA naïve patients, was 90%; including 10
patients (34%) with Complete Remission (CR). Among the 26 evaluable
HMA-failed patients the ORR was 54% including 8% CR or PR. The
median time to initial and best response were 1 and 4 cycles in the
HMA naïve group and 2 and 5 cycles in the HMA failed group.
The safety population (n = 74) received at least
1 dose of oral rigosertib. The combination was well tolerated.
Other than genitourinary adverse events (AEs), the AE profile was
similar to those described for azacitidine alone in this patient
population. Genitourinary AEs, including hematuria (45% incidence
of all grades, including 9% grade 3, and dysuria (38% all grades
and 9% grade 3) were observed. A Safety Optimization Strategy
was implemented for the higher dose cohort of 1,120 mg of oral
rigosertib. These strategies included earlier in the day
administration of the PM dose, oral hydration, monitoring of
urinary pH and mandatory bladder emptying at night. Collectively
these strategies resulted in mitigation of the target genitourinary
AEs, including reduction of genitourinary grade 3 AEs reported from
an earlier cohort despite receiving a higher dose of oral
rigosertib.
In conclusion, oral rigosertib in combination
with azacitidine was well tolerated in HMA naïve and HMA failed
HR-MDS patients. The combination produced an encouraging rate
of overall response and complete remission in both groups. The
safety optimization strategies and increased dose exploration of
oral rigosertib in the combination is leading to the development of
a pivotal Phase 3 trial in HMA and chemotherapy naïve
patients.
Drs. Lewis Silverman and Guillermo Garcia
Manero, the lead investigators of the study at Mount Sinai Medical
Center and MD Anderson Cancer Center, respectively, commented,
“This multi-institutional collaborative study based on earlier
laboratory research showing synergistic activity of rigosertib in
combination with azacitidine led to a clinical trial of this
combination in higher-risk MDS patients for both HMA naive and
failed patients. The high overall response rate reported
today is impressive, as is the durability and rate of achieving
complete remission. We are excited about progressing these studies
to a randomized pivotal placebo-controlled Phase 3 trial. The
overall tolerability of the combination and convenience of
administration of oral rigosertib could be key advantages for these
future studies.”
Dr. Steve Fruchtman, President of Onconova
Therapeutics, Inc, sponsor of this study and developer of
rigosertib commented, “We are most grateful to the patients, their
families and our dedicated collaborating investigators for their
participation in this study. The impressive results presented here
have led to our plan for a pivotal trial for these patients
ultimately hoping to improve upon their current therapeutic
options. Based on End of Phase 2 Meetings with the Health
Authorities, we have developed a randomized controlled pivotal
trial. We expect to start the regulatory process for the approval
of this trial plan very shortly. We are hopeful that both
intravenous and oral formulations of rigosertib will be useful in
serving the needs of higher risk MDS patients.”
This oral presentation was delivered by Shyamala
Navada, MD, Mount Sinai Medical Center on Saturday, December 1,
2018.
A copy of the presentation is available by
visiting the Scientific Presentations section of Onconova’s
website.
Onconova plans to meet with the FDA to discuss
the results of the Phase 2 trial and the planned Phase 3 trial, and
to seek a Special Protocol Assessment. The Company has partnered
rigosertib with SymBio Pharmaceuticals, for Japan and Korea, and
with Pint Pharma for Latin American countries. Both partners have
indicated their interest in participating in the proposed new
pivotal Phase 3 trial by enrolling patients in their respective
territories. SymBio is currently conducting Phase 1 studies with
oral rigosertib in Japan and also participating in the Phase 3
global INSPIRE trial. The Company is also actively seeking
additional collaborations for rigosertib in other geographies.
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 is reported to block 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. 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 a randomized Phase 3 international
INSPIRE trial for patients with higher-risk MDS, after failure of
hypomethylating agent, or HMA, therapy.
About INSPIRE The
INternational Study of
Phase III IV
RigosErtib, or INSPIRE, 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 9 cycles over the course of one
year after initiation and with progression or failure to respond to
HMA treatment. This time frame optimizes the opportunity to respond
to treatment with an HMA prior to declaring treatment failure, as
per NCCN Guidelines. Following interim analysis in early 2018, the
independent Data Monitoring Committee recommended that the trial
continue with an expansion in enrollment to 360 patients based on a
pre-planned sample size re-estimation. Patients are 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. 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
where the duration of treatment may extend for years in lower risk
MDS patients. This dosage form may also support 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 U.S. 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
Onconova expectations regarding the INSPIRE Trial and Onconova’s
other development plans. 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. 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.
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, 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 Mark Guerin
Onconova Therapeutics, Inc. 267-759-3680
http://www.onconova.com/contact/
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