PDUFA target action date is June 30, 2025
If approved, avutometinib in combination with
defactinib would be the first-ever FDA-approved treatment
specifically for adults with recurrent KRAS mutant LGSOC
Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company
committed to advancing new medicines for patients with cancer,
today announced that the U.S. Food and Drug Administration (FDA)
has accepted for review the New Drug Application (NDA) under the
accelerated approval pathway for avutometinib, an oral RAF/MEK
clamp, in combination with defactinib, an oral FAK inhibitor, for
the treatment of adult patients with recurrent low-grade serous
ovarian cancer (LGSOC), who received at least one prior systemic
therapy and have a KRAS mutation. The NDA, which was completed in
October 2024, has been granted Priority Review with a Prescription
Drug User Fee Act (PDUFA) action date of June 30, 2025. In
addition, the FDA has stated that it is not currently planning to
hold an advisory committee meeting to discuss the application.
“The FDA filing acceptance and Priority Review for the
combination of avutometinib and defactinib underscores the critical
unmet need among patients diagnosed with this rare and insidious
disease. We are excited by today’s news and to potentially bring
the first ever FDA-approved treatment specifically for recurrent
KRAS mutant LGSOC to patients in the U.S.,” said Dan Paterson,
president and chief executive officer of Verastem Oncology. “With
the acceptance of this NDA, we’re taking an important step forward
in addressing a condition that has long been overlooked, and we
look forward to working with the FDA during its review process and
preparing for a commercial launch in mid-2025.”
There are currently no FDA-approved treatments specifically for
LGSOC, a rare and distinct ovarian cancer that differs from
high-grade serous ovarian cancer in both its biology and how it
responds to treatment. Priority Review is granted by the FDA for
treatments that offer, if approved, significant improvements over
available options or that provide a treatment option where no
adequate or approved therapy currently exists.
The filing was based on a primary analysis of the Phase 2 RAMP
201 clinical trial that evaluated the combination of avutometinib
and defactinib in patients with recurrent LGSOC. The results were
presented in an oral presentation at the International Gynecologic
Cancer Society (IGCS) Annual Global Meeting in October 2024 and
demonstrated that the combination of avutometinib plus defactinib
resulted in a substantial overall response rate confirmed by
blinded independent central review, with responses that were
typically durable, and that the combination was generally
well-tolerated in patients with recurrent KRAS mutant LGSOC. The
NDA also includes supportive data from the FRAME Phase 1 trial, the
first study conducted with the combination therapy in recurrent
LGSOC.
The Company is currently enrolling patients with recurrent LGSOC
regardless of KRAS mutation status for RAMP 301, an international
Phase 3 trial, which will serve as a confirmatory study for the
initial indication and has the potential to support an expanded
indication regardless of KRAS mutation status.
About RAMP 201
RAMP 201 (ENGOTov60/GOG3052) (NCT04625270) is an adaptive,
two-part multicenter, parallel cohort, randomized, open-label Phase
2 registration-directed trial evaluating the efficacy and safety of
avutometinib alone and in combination with defactinib in patients
with recurrent low-grade serous ovarian cancer (LGSOC). The first
part of the study (Part A) determined the selection of the
go-forward regimen, which was the combination of avutometinib and
defactinib versus avutometinib alone, based on overall response
rates. The expansion phases of the trial (Parts B and C) are
evaluating the safety and efficacy of the go-forward regimen of
avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily.
The Part D portion of the trial is evaluating a low dose of
avutometinib in combination with defactinib to inform
individualized dose reduction.
About Low-Grade Serous Ovarian Cancer (LGSOC)
LGSOC is a rare ovarian cancer that is insidious, persistent,
and ultimately fatal. LGSOC is distinct and different from
high-grade serous ovarian cancer (HGSOC) and requires different
treatment. LGSOC is highly recurrent and less sensitive to
chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in
the U.S. and 80,000 worldwide are living with this disease. LGSOC
affects younger women with bimodal peaks of diagnosis at ages
between 20-30 and 50-60 and has a median survival of approximately
ten years. The majority of patients report a negative impact of
LGSOC on their mental and physical health, fertility, and long-term
quality of life. The current standard of care for this disease
includes hormone therapy and chemotherapy, but there are no
treatments specifically approved by the U.S. Food and Drug
Administration to treat LGSOC.
About the Avutometinib and Defactinib Combination
Avutometinib is an oral RAF/MEK clamp that potentially inhibits
MEK1/2 kinase activities and induces inactive complexes of MEK with
ARAF, BRAF, and CRAF, potentially creating a more complete and
durable anti-tumor response through maximal RAS/MAPK pathway
inhibition. In contrast to currently available MEK-only inhibitors,
avutometinib blocks both MEK kinase activity and the ability of RAF
to phosphorylate MEK. This unique mechanism allows avutometinib to
block MEK signaling without the compensatory activation of MEK that
appears to limit the efficacy of the MEK-only inhibitors.
Defactinib is an oral, selective inhibitor of focal adhesion
kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2), the two
members of the focal adhesion kinase family of non-receptor protein
tyrosine kinases. FAK and Pyk2 integrate signals from integrin and
growth factor receptors to regulate cell proliferation, survival,
migration, and invasion. FAK activation has been shown to mediate
resistance to multiple anti-cancer agents, including RAF and MEK
inhibitors.
Verastem Oncology is currently conducting clinical trials with
avutometinib with and without defactinib in RAS/MAPK-driven tumors
as part of its Raf And Mek Program or
RAMP. Verastem is currently enrolling patients and activating sites
for RAMP 301 (GOG-3097/ENGOT-ov81/NCRI) (NCT06072781), an
international Phase 3 confirmatory trial evaluating the combination
of avutometinib and defactinib versus standard chemotherapy or
hormonal therapy for the treatment of recurrent low-grade serous
ovarian cancer (LGSOC).
Verastem was granted Priority Review and a Prescription Drug
User Fee Act (PDUFA) date of June 30, 2025, for its New Drug
Application (NDA) to the U.S. Food and Drug Administration (FDA),
for the investigational combination of avutometinib and defactinib
in adults with recurrent KRAS mutant LGSOC who received at least
one prior systemic therapy. Verastem initiated a rolling NDA in May
2024 to the FDA and completed its NDA submission in October 2024.
The FDA granted Breakthrough Therapy Designation for the treatment
of patients with recurrent LGSOC after one or more prior lines of
therapy, including platinum-based chemotherapy, in May 2021.
Avutometinib alone or in combination with defactinib was also
granted Orphan Drug Designation by the FDA for the treatment of
LGSOC.
Verastem Oncology has established a clinical collaboration with
Amgen to evaluate LUMAKRAS™ (sotorasib) in combination with
avutometinib and defactinib in both treatment-naïve patients and in
patients whose KRAS G12C mutant non-small cell lung cancer
progressed on a G12C inhibitor as part of the RAMP 203 trial
(NCT05074810). Verastem has received Fast Track Designation from
the FDA for the triplet combination in April 2024. RAMP 205
(NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib
and defactinib with gemcitabine/nab-paclitaxel in patients with
front-line metastatic pancreatic cancer, is supported by the PanCAN
Therapeutic Accelerator Award. FDA granted Orphan Drug Designation
to the avutometinib and defactinib combination for the treatment of
pancreatic cancer.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a late-stage development
biopharmaceutical company committed to the development and
commercialization of new medicines to improve the lives of patients
diagnosed with cancer. Our pipeline is focused on RAS/MAPK-driven
cancers, specifically novel small molecule drugs that inhibit
critical signaling pathways in cancer that promote cancer cell
survival and tumor growth, including RAF/MEK inhibition and FAK
inhibition. For more information, please visit www.verastem.com and
follow us on LinkedIn.
Forward-Looking Statements
This press release includes forward-looking statements about,
among other things, Verastem Oncology’s programs and product
candidates, strategy, future plans, and prospects, including
statements related to the expected timing of the FDA action on the
New Drug Application (NDA) for the avutometinib and defactinib
combination product in KRAS-mutant and recurrent low-grade serous
ovarian cancer, the potential clinical value of various of the
Company’s clinical trials, including the RAMP 201, RAMP 203, RAMP
205 and RAMP 301 trials, the timing of commencing and completing
trials and compiling data, including topline data and reports,
interactions with regulators, the potential for and timing of
commercialization of product candidates and potential for
additional development programs involving Verastem Oncology’s lead
compound. The words "anticipate," "believe," "estimate," "expect,"
"intend," "may," "plan," "predict," "project," "target,"
"potential," "will," "would," "could," "should," "continue," “can,”
“promising” and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words.
Forward-looking statements are not guarantees of future
performance and are subject to risks and uncertainties that could
cause our actual results to differ materially from those expressed
or implied in the forward-looking statements we make. Applicable
risks and uncertainties include the risks and uncertainties, among
other things, regarding: the success in the development and
potential commercialization of our product candidates, including
avutometinib in combination with other compounds, including
defactinib, LUMAKRAS™ and others; the uncertainties inherent in
research and development, such as negative or unexpected results of
clinical trials, the occurrence or timing of applications for our
product candidates that may be filed with regulatory authorities in
any jurisdictions; whether and when regulatory authorities in any
jurisdictions may approve or reject any such applications that may
be filed for our product candidates, and, if approved, whether our
product candidates will be commercially successful in such
jurisdictions; our ability to obtain, maintain and enforce patent
and other intellectual property protection for our product
candidates; the scope, timing, and outcome of any legal
proceedings; decisions by regulatory authorities regarding trial
design, labeling and other matters that could affect the timing,
availability or commercial potential of our product candidates;
whether preclinical testing of our product candidates and
preliminary or interim data from clinical trials is predictive of
the results or success of ongoing or later clinical trials; the
uncertainty around the timing, scope and rate of reimbursement for
our product candidates; internal and third-party estimates about
the market opportunities of our drug candidates may prove to be
incorrect; third-party payors (including government agencies) may
not reimburse; there may be competitive developments affecting our
product candidates; data may not be available when expected; that
enrollment of clinical trials may take longer than expected, which
may delay our development programs, including delays in review by
the FDA of our NDA submission in recurrent KRAS mutant LGSOC if
enrollment in our confirmatory trial is not well underway at the
time of submission, or that the FDA may require the Company to have
completed enrollment or to enroll additional patients in the
Company’s ongoing RAMP-301 confirmatory Phase 3 clinical trial
prior to the FDA taking action on our NDA seeking accelerated
approval; risks associated with preliminary and interim data, which
may not be representative of more mature data, including with
respect to interim duration of therapy data; our product candidates
may cause adverse safety events and/or unexpected concerns may
arise from additional data or analysis, or result in unmanageable
safety profiles as compared to their levels of efficacy; we may be
unable to successfully validate, develop and obtain regulatory
approval for companion diagnostic tests for our product candidates
that require or would commercially benefit from such tests, or
experience significant delays in doing so; the mature RAMP 201 data
and associated discussions with the FDA may not support the scope
of our NDA submission for the avutometinib and defactinib
combination in LGSOC, including with respect to both recurrent KRAS
mutant and recurrent KRAS wild type LGSOC; our product candidates
may experience manufacturing or supply interruptions or failures;
any of our third party contract research organizations, contract
manufacturing organizations, clinical sites, or contractors, among
others, who we rely on may fail to fully perform; we face
substantial competition, which may result in others developing or
commercializing products before or more successfully than we do
which could result in reduced market share or market potential for
our product candidates; we may be unable to successfully initiate
or complete the clinical development and eventual commercialization
of our product candidates; the development and commercialization of
our product candidates may take longer or cost more than planned,
including as a result of conducting additional studies or our
decisions regarding execution of such commercialization; we may not
have sufficient cash to fund our contemplated operations, including
certain of our product development programs; we may not attract and
retain high quality personnel; we or Chugai Pharmaceutical Co.,
Ltd. may fail to fully perform under the avutometinib license
agreement; the total addressable and target markets for our product
candidates might be smaller than we are presently estimating; we or
Secura Bio, Inc. (Secura) may fail to fully perform under the asset
purchase agreement with Secura, including in relation to milestone
payments; we may not see a return on investment on the payments we
have and may continue to make pursuant to the collaboration and
option agreement with GenFleet Therapeutics (Shanghai), Inc.
(GenFleet), or that GenFleet may fail to fully perform under the
agreement; we may not be able to establish new or expand on
existing collaborations or partnerships, including with respect to
in-licensing of our product candidates, on favorable terms, or at
all; we may be unable to obtain adequate financing in the future
through product licensing, co-promotional arrangements, public or
private equity, debt financing or otherwise; we may not pursue or
submit regulatory filings for our product candidates; and our
product candidates may not receive regulatory approval, become
commercially successful products, or result in new treatment
options being offered to patients.
Other risks and uncertainties include those identified under the
heading “Risk Factors” in the Company’s Annual Report on Form 10-K
for the year ended December 31, 2023, as filed with the Securities
and Exchange Commission (SEC) on March 14, 2024, and in any
subsequent filings with the SEC, which are available at
www.sec.gov. The forward-looking statements contained in this press
release reflect Verastem Oncology’s views as of the date hereof,
and the Company does not assume and specifically disclaims any
obligation to update any forward-looking statements, whether as a
result of new information, future events, or otherwise, except as
required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20241230294719/en/
For Investor and Media Inquiries: Julissa Viana Vice
President, Corporate Communications and Investor Relations
investors@verastem.com or media@verastem.com
Verastem (NASDAQ:VSTM)
過去 株価チャート
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Verastem (NASDAQ:VSTM)
過去 株価チャート
から 1 2024 まで 1 2025
