--35% Complete Remission (CR)
Rate for Combination in 1st-line
Higher-risk MDS Patients--
Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage
biopharmaceutical company focused on discovering and developing
novel products to treat cancer, today announced the presentation of
data from a Phase 2 clinical trial of oral rigosertib and
azacitidine in higher-risk myelodysplastic syndromes (HR-MDS) at
the 58th American Society of Hematology (ASH) Annual Meeting in San
Diego, California.
“The complete remission rate amongst HMA-naïve
HR-MDS patients is higher and responses occur more rapidly and
durably with the oral rigosertib combination compared to historic
single-agent azacitidine,” commented Lewis R. Silverman, M.D., lead
investigator in the trial and Associate Professor of Medicine,
Hematology and Medical Oncology, at the Icahn School of Medicine at
Mount Sinai. “Furthermore, the addition of oral rigosertib to
azacitidine does not substantially change the adverse event profile
of single-agent azacitidine, and thus may overcome the limitations
identified in other HMA-based combinations.”
The current standard of care for higher-risk MDS
patients is one of two approved hypomethylating agents (azacitidine
and decitabine, approved by the FDA in 2004 and 2006). Although
these drugs are currently the standard of care in HR-MDS therapy,
their overall response rate and duration of benefit is limited to a
subset of eligible patients and all responding patients ultimately
progress. Thus, there is an urgent need for improving therapeutic
options for newly diagnosed HR-MDS patients. The 09-08 trial tested
oral rigosertib in combination with injectable azacitidine in a
dose ranging study (Phase 1), followed by an expansion cohort
(Phase 2) to evaluate the efficacy and safety of the combination.
Both 1st-line and 2nd-line HR-MDS patients were included in the
study.
Summary of Presented Data from the 09-08
Combination Therapy Trial
Patient Demographics:
- Thirty-three of 40 MDS patients enrolled were evaluable for
response at the time of this analysis.
- The median age was 66, with 73% of male patients. ECOG
performance status was 0 or 1 in 95% of the patients. IPSS-R
distribution was: 7.5% Low, 12.5% Intermediate, 37.5% High,
32.5% Very High and 10% unknown.
Safety/Tolerability of the Combination:
- Oral rigosertib (560 mg qAM, 280 mg qPM) was administered on
Day 1-21 of a 28-day cycle. Azacitidine 75 mg/m2/day SC or IV was
administered for 7 days starting on Day 8.
- The combination of oral rigosertib and azacitidine was well
tolerated.
- Adverse events of Grade ≥3 experienced across all cycles with
the combination included thrombocytopenia (33%), neutropenia (30%),
haematuria (13%), dysuria (8%), diarrhoea (3%) and arthralgia
(3%).
- Notably, the side effects were similar to those previously
reported for azacitidine administered alone.
Efficacy of the Combination:
- Thirty-three (20 HMA naïve; 13 HMA resistant) MDS patients were
evaluable for efficacy analysis per IWG 2006 criteria (Cheson et
al., Blood 2006).
- 25 of 33 (76%) patients responded per IWG – 85% of HMA naïve
patients experienced a response and 62% of HMA resistant patients
experienced a response.
- 7 of 20 (35%) HMA naïve and 1 of 13 (8%) HMA-resistant patients
achieved a complete remission (CR). The median duration of CR was
8.0 months, which compares very favorably to the historic duration
of CR and PR with single-agent azacitidine of 3.2 months1.
- Hematologic improvement (HI) was observed in 11 of 33 patients
(33%) and the median duration of response was 7.4 months for
erythroid response, 8 months for platelet response, and 6.2 months
for neutrophil response. Marrow CR was observed in 16 of 33 (48%)
patients and the median duration of response was 12.3 months.
Marrow CR combined with HI was observed in 10 of 33 (30%)
patients.
The poster entitled, “Combination of Oral
Rigosertib and Injectable Azacitidine in Patients with
Myelodysplastic Syndromes (MDS): Results from a Phase II Study,”
was presented by Dr. Shyamala Navada of Mount Sinai School of
Medicine at the Myelodysplastic Syndromes Session on Sunday,
December 4, 2016 at the ASH Annual Meeting in San Diego,
California. A copy of the poster is available by visiting the
Scientific Presentations section under the Investors & Media
tab of Onconova’s website.
“We are pleased by the positive efficacy signal
observed over extended periods of treatment, and the acceptable
tolerability of oral rigosertib and azacitidine in 1st-line
HR-MDS,” stated Ramesh Kumar, Ph.D., President and CEO of
Onconova. “We presented Phase 2 data to the FDA as part of
our End-of-Phase 2 meeting in September 2016, and based on these
discussions, we are designing a randomized, placebo controlled
Phase 3 clinical trial comparing the combination of oral rigosertib
plus azacitidine to azacitidine plus placebo in 1st-line HR-MDS
patients with the primary composite endpoint of CR and PR rate per
2006 IWG criteria. Based on our discussions with the FDA the
primary efficacy endpoint of this trial will be composite response
and not survival, permitting accelerated evaluation of
outcomes.”
Comprehensive Safety Assessment of
Rigosertib in MDS Patients
In a second poster at the conference a safety
review of 557 MDS/AML patients treated with rigosertib in clinical
studies, including the randomized Phase 3 ONTIME trial was
presented. The poster entitled, “Comprehensive Analysis of
Safety: Rigosertib in 557 Patients with Myelodysplastic Syndromes
(MDS) and Acute Myeloid Leukemia (AML),” can be accessed by
visiting the Scientific Presentations section under the Investors
& Media tab of Onconova’s website.
About Onconova Therapeutics,
Inc.
Onconova Therapeutics is a Phase 3
clinical-stage biopharmaceutical company focused on discovering and
developing novel products to treat cancer. Onconova's clinical and
pre-clinical stage drug development candidates are derived from its
extensive chemical library and are designed to work against
specific cellular pathways that are important in cancer cells,
while causing minimal damage to normal cells. The Company’s most
advanced product candidate, rigosertib, is a small molecule
inhibitor of cellular signaling and acts as a RAS mimetic. These
effects of rigosertib appear to be mediated by direct binding of
the compound to the RAS-binding domain (RBD) found in many RAS
effector proteins, including the Raf and PI3 kinases. Rigosertib is
protected by issued patents (earliest expiry in 2026) and has been
awarded Orphan Designation for MDS in the United States, Europe and
Japan. In addition to rigosertib, two other candidates are in
the clinical stage, and several candidates are in pre-clinical
stages. For more information, please
visit http://www.onconova.com.
About Oral Rigosertib
The oral form of rigosertib provides a more
convenient dosing for use where the duration of treatment may
extend to multiple years. To date, more than 350 patients have been
treated with the oral formulation of rigosertib, either as a single
agent or in combination with other drugs. Phase 1 studies
with 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.
About IV Rigosertib
The intravenous form of rigosertib has been
employed in Phase 1, 2, and 3 clinical trial involving more than
800 patients, and is currently being evaluated in the randomized
Phase 3 global INSPIRE trial as 2nd-line treatment for patients
with higher-risk MDS, after failure of hypomethylating agent, or
HMA, therapy. This formulation is suited for patients with advanced
disease and provides long duration of exposure and ensures adequate
dosing under a controlled setting.
References
1Fenaux et al for the international Vidaza High
risk MDS survival study group, Lancet Oncology 2009,
10:223-232.
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, which 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,” “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 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.
CONTACT:
Onconova Therapeutics
Benjamin Hoffman, 267-759-3036
bhoffman@onconova.us
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