- Tivozanib Significantly Improves PFS and ORR
Compared to Sorafenib and Demonstrates Updated Interim OS HR of
0.99 in Refractory Advanced RCC -
- Outcomes Favor Tivozanib in Patients
Previously Treated With Checkpoint Inhibitors as Well as Two
VEGFR-TKIs -
- Data Featured in Oral Presentation at the
18th International Kidney Cancer Symposium -
AVEO Oncology (NASDAQ: AVEO) today announced the presentation of
updated data from the Phase 3 TIVO-3 trial. The data were presented
on Saturday, November 16, 2019, at the 18th International Kidney
Cancer Symposium in Miami, in an oral presentation titled “TIVO-3:
A Phase 3 Study to Compare Tivozanib to Sorafenib in Subjects with
Refractory Advanced Renal Cell Carcinoma (RCC) Overall Survival
2-Year Update” by Sumanta (Monty) Kumar Pal, M.D., Associate
Clinical Professor, Department of Medical Oncology and Therapeutics
Research, and Co-director, Kidney Cancer Program, at City of Hope
Comprehensive Cancer Center. TIVO-3 is the Company’s Phase 3
randomized, controlled, multi-center, open-label study to compare
tivozanib (FOTIVDA®), the Company’s vascular endothelial growth
factor receptor tyrosine kinase inhibitor (VEGFR-TKI), to sorafenib
in 350 subjects with highly refractory metastatic RCC.
As previously presented, results for the intent to treat (ITT)
population showed that tivozanib significantly improved progression
free survival (PFS), the study’s primary endpoint, and overall
response rate (ORR) compared to sorafenib, with responses to
tivozanib more durable than sorafenib. Newly presented data include
the recently announced interim overall survival (OS) hazard ratio
(HR) of 0.99 within the ITT population, as well as results from two
prespecified subgroup analyses of patients previously treated with
a checkpoint inhibitor and a VEGF-TKI, or two VEGFR-TKIs. Superior
PFS and ORR, as well as OS HRs below 1, favoring tivozanib, were
observed in the prespecified subgroups. Tivozanib was shown to have
lower overall rates of adverse events and fewer dose interruptions
and reductions versus sorafenib, indicating better patient
tolerability. A copy of the presentation is available in the
Publications & Presentations section of AVEO’s website.
“Until the TIVO-3 trial results, limited prospective data
existed to inform sequencing of treatment after checkpoint
inhibitor therapy, the emergent standard of care in earlier-line
treatment,” said Dr. Pal. “Tivozanib’s outcomes within this
population, as well as in those receiving two prior VEGF-TKIs,
suggest an important potential role for tivozanib in the evolving
refractory advanced RCC setting. Furthermore, tivozanib’s unique
tolerability profile is potentially well suited to an advanced
setting, where many are reluctant to accept higher rates of adverse
events following multiple courses of therapy.”
“Tivozanib is the first RCC treatment to show superior outcomes
over another active therapy in a Phase 3 study in the third/fourth
line setting, a high unmet need population that is growing due to
longer survival in earlier lines of therapy,” said Michael Bailey,
president and chief executive officer of AVEO. “We look forward to
completing a final OS analysis of TIVO-3 in June 2020 after our
planned submission of a new drug application (NDA) to the U.S. Food
and Drug Administration (FDA) in the first quarter of 2020. The
continued separation of the PFS curves and the positive trend in OS
HR observed from the first to the second interim analyses of
TIVO-3, together with tenfold more patients remaining progression
free and on tivozanib vs. sorafenib therapy, make us believe that
the final OS HR could continue to improve.”
AVEO recently provided a regulatory update following a meeting
with the FDA to discuss results from the August 2019 OS analysis of
the TIVO-3 trial. The Company intends to submit an update to the
TIVO-3 statistical analysis plan to the FDA allowing for the final
OS analysis to be conducted, followed by an NDA submission in the
first quarter of 2020, and expects to report results from a final
OS analysis of the TIVO-3 trial in June 2020. The FDA and the
Company agreed that if, during the review, the final analysis
yields an OS HR above 1.00, the Company will withdraw its NDA
application. The FDA informed the Company that an Oncologic Drugs
Advisory Committee panel would likely be convened to review the
final tivozanib data package.
Results in Detail
Patients enrolled in the TIVO-3 trial (n=350) were randomized
and stratified for prior regimen and IMDC prognostic score. Prior
treatment regimens included prior checkpoint inhibitor and VEGF TKI
therapies (n=91), two prior VEGF TKI therapies (n=159) and prior
VEGF TKI and other therapies (n=100). Statistically significant
improvements favoring tivozanib were reported for the primary
endpoint of PFS (HR=0.73; p=0.0165) and secondary endpoint of ORR
(18% vs. 8%; p=0.02). Improvements were also observed in patients
receiving prior checkpoint inhibitor and VEGF TKI therapies and two
prior VEGF TKI therapies:
Prior Checkpoint Inhibitor +
VEGFR TKI
Tivozanib
(n=47)
Sorafenib
(n=44)
Median PFS, months (95% CI)
7.3 (4.8, 11.1)
5.1 (3.2, 7.4)
PFS HR (95% CI)
0.55 (0.32, 0.94)
P Value
0.028
ORR
24.4%
6.8%
OS HR
0.88
Two Prior VEGFR TKIs
Tivozanib
(n=79)
Sorafenib
(n=80)
Median PFS, months (95% CI)
5.5 (3.6, 7.4)
3.7 (3.6, 3.9)
PFS HR (95% CI)
0.57 (0.39, 0.83)
P Value
0.003
ORR
15.2%
7.5%
OS HR
0.98
For the secondary endpoint of OS, two prespecified analyses have
been conducted, the first at a data cutoff date of October 4, 2018,
and the second at August 15, 2019. The OS HR, which assesses the
relative risk of death for the entirety of the data set, was 0.99
(95% CI: 0.76-1.29; p=0.95) for the ITT population at the second
analysis, and improvement from an HR of 1.12 observed at the first
analysis. At the second analysis, OS HR for patients receiving
prior checkpoint inhibitor and VEGF TKI therapies was 0.88, and
0.98 for patients treated with two prior VEGF TKI therapies. Both
hazard ratios were improved from hazard ratios of 1.14 and 1.05,
respectively, observed at the first analysis.
As of the August 15, 2019 data cutoff date, median OS, a point
in time value of the OS when half of the patients within each arm
are still alive, was 16.4 months for tivozanib (95% CI: 13.4-22.2)
and 19.7 months for sorafenib (95% CI: 15.0-24.2). As of the second
data cutoff date, twenty patients remained progression free on the
tivozanib arm and two on the sorafenib arm, with a median duration
on study of 32.5 months.
Grade 3 or higher adverse events were consistent with those
observed in previous tivozanib trials. Infrequent but severe
adverse events reported in greater number in the tivozanib arm were
thrombotic events similar to those observed in previous tivozanib
studies. The most common adverse event in patients receiving
tivozanib was hypertension, an adverse event known to reflect
effective VEGF pathway inhibition.
About Tivozanib (FOTIVDA®)
Tivozanib (FOTIVDA®) is an oral, once-daily, vascular
endothelial growth factor receptor (VEGFR) tyrosine kinase
inhibitor (TKI) discovered by Kyowa Kirin and approved for the
treatment of adult patients with advanced renal cell carcinoma
(RCC) in the European Union plus Norway, New Zealand and Iceland.
It is a potent, selective and long half-life inhibitor of all three
VEGF receptors and is designed to optimize VEGF blockade while
minimizing off-target toxicities, potentially resulting in improved
efficacy and minimal dose modifications.1,2 Tivozanib is being
studied in the TIVO-3 trial, which is intended to support a
regulatory submission of tivozanib in the U.S. as a treatment for
relapsed/refractory RCC. Tivozanib has been shown to significantly
reduce regulatory T-cell production in preclinical models3 and has
demonstrated synergy in combination with nivolumab (anti PD-1) in a
Phase 2 study in RCC4. Tivozanib has been investigated in several
tumor types, including renal cell, hepatocellular, colorectal,
ovarian and breast cancers.
About AVEO
AVEO Pharmaceuticals is a biopharmaceutical company seeking to
advance targeted medicines for oncology and other unmet medical
needs. The Company’s lead candidate is tivozanib, a potent,
selective, long half-life inhibitor of vascular endothelial growth
factor 1, 2 and 3 receptors, which AVEO is seeking to develop and
commercialize in North America as a treatment for renal cell
carcinoma (RCC), hepatocellular carcinoma (HCC) and other cancers.
Tivozanib (FOTIVDA®) is approved by the European Commission for the
treatment of adult patients with advanced RCC in the European Union
plus Norway, New Zealand and Iceland. AVEO is leveraging or seeks
to leverage partnerships to develop and commercialize its pipeline
of products and product candidates, including tivozanib in oncology
and other indications in various geographies, and ficlatuzumab (HGF
MAb) in head and neck cancer, pancreatic cancer and acute myeloid
leukemia. AVEO’s earlier-stage pipeline includes AV-203 (anti-ErbB3
MAb), AV-380 (GDF15 MAb) and AV-353 (Notch 3 MAb) drug candidates
being developed for various oncology indications.
For more information, please visit the Company’s website at
www.aveooncology.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements of AVEO
within the meaning of the Private Securities Litigation Reform Act
of 1995 that involve substantial risks and uncertainties. All
statements, other than statements of historical fact, contained in
this press release are forward-looking statements. The words
“anticipate,” “believe,” “expect,” “intend,” “may,” “plan,”
“potential,” “could,” “should,” “would,” “seek,” “look forward,”
“advance,” “goal,” “strategy,” or the negative of these terms or
other similar expressions, are intended to identify forward-looking
statements, although not all forward-looking statements contain
these identifying words. These forward-looking statements include,
among others, statements about: AVEO’s plans to submit an update to
the TIVO-3 statistical analysis plan to the FDA allowing for the
final OS analysis to be conducted, followed by a planned NDA
submission in the first quarter of 2020; AVEO’s expectations that
it will report results from a final OS analysis of the TIVO-3 trial
in June 2020; AVEO’s belief that the final OS HR in TIVO-3 could
continue to improve; the potential for tivozanib as a treatment
option for patients with relapsed/refractory or refractory advanced
RCC, hepatocellular carcinoma and other cancers; the potential
efficacy, safety, and tolerability of tivozanib, both as
stand-alone drug candidate and in combination with other therapies
; AVEO’s expectation that TIVO-3 is intended to support a
regulatory submission of tivozanib in the U.S. as a treatment for
relapsed/refractory RCC; AVEO’s plans and strategies for
commercialization of tivozanib in the United States and Europe; and
AVEO’s other strategies, prospects, plans and objectives for its
product candidates and for the Company generally. AVEO has based
its expectations and estimates on assumptions that may prove to be
incorrect. As a result, readers are cautioned not to place undue
reliance on these expectations and estimates. Actual results or
events could differ materially from the plans, intentions and
expectations disclosed in the forward-looking statements that AVEO
makes due to a number of important factors, including risks
relating to: AVEO’s ability, and the ability of its licensees, to
demonstrate to the satisfaction of applicable regulatory agencies
such as the FDA the safety, efficacy and clinically meaningful
benefit of AVEO’s product candidates, including, in particular,
tivozanib and ficlatuzumab; AVEO’s ability to successfully file an
NDA for tivozanib; and AVEO’s ability to enter into and maintain
its third party collaboration and license agreements, and its
ability, and the ability of its strategic partners, to achieve
development and commercialization objectives under these
arrangements. AVEO faces other risks relating to its business as
well, including risks relating to the timing and costs of seeking
and obtaining regulatory approval; AVEO’s and its collaborators’
ability to successfully enroll and complete clinical trials; AVEO’s
ability to maintain compliance with regulatory requirements
applicable to its product candidates; AVEO’s ability to obtain and
maintain adequate protection for intellectual property rights
relating to its product candidates; AVEO’s ability to successfully
implement its strategic plans; AVEO’s ability to raise the
substantial additional funds required to achieve its goals,
including those goals pertaining to the development and
commercialization of tivozanib; unplanned capital requirements;
adverse general economic and industry conditions; competitive
factors; and those risks discussed in the sections titled “Risk
Factors” and “Management’s Discussion and Analysis of Financial
Condition and Results of Operations—Liquidity and Capital
Resources” included in AVEO’s quarterly and annual reports on file
with the Securities and Exchange Commission (SEC) and in other
filings that AVEO makes with the SEC. The forward-looking
statements in this press release represent AVEO’s views as of the
date of this press release, and subsequent events and developments
may cause its views to change. While AVEO may elect to update these
forward-looking statements at some point in the future, it
specifically disclaims any obligation to do so. You should,
therefore, not rely on these forward-looking statements as
representing AVEO's views as of any date other than the date of
this press release.
References
1. Fotivda (Tivozanib) SmPC August 2017 2. Motzer RJ, Nosov D,
Eisen T, et al. J Clin Oncol 2013; 31(30): 3791-9. 3. Pawlowski N
et al. AACR 2013. Poster 3971. 4. Barthelemy et al. ESMO 2018.
Poster 878P
View source
version on businesswire.com: https://www.businesswire.com/news/home/20191118005252/en/
AVEO: David Pitts, Argot Partners (212) 600-1902
aveo@argotpartners.com
AVEO Pharmaceuticals (NASDAQ:AVEO)
Historical Stock Chart
From Aug 2024 to Sep 2024
AVEO Pharmaceuticals (NASDAQ:AVEO)
Historical Stock Chart
From Sep 2023 to Sep 2024