Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology
company creating a new class of drugs based on targeted protein
degradation, today announced the presentation of interim data from
the Company’s Phase 1/2 clinical trial for bavdegalutamide
(ARV-110), a novel PROTAC® protein degrader targeting the androgen
receptor (AR), in a poster session at the European Society for
Medical Oncology Congress being held in Madrid from October 20 –
24, 2023. The Company will host a conference call to discuss these
data and present new data from an updated analysis of its ongoing
Phase 1/2 clinical trial with its second-generation PROTAC AR
degrader, ARV-766, showing clinical activity extending across
patients harboring tumors with AR LBD mutations and a tolerability
profile that is superior to bavdegalutamide.
Extended follow-up of data from the Phase 1/2 clinical trial
with bavdegalutamide showed radiographic progression free survival
(rPFS) of 11.1 months in a subgroup of patients with metastatic
castration-resistant prostate cancer (mCRPC) and tumors harboring
AR T878X/H878Y mutations (AR 878/875; T878X=T878A or T878S) in the
absence of co-occurring AR L702H mutations. AR L702H is a common AR
ligand-binding domain (LBD) mutation that is not potently degraded
by bavdegalutamide. In patients with tumors harboring any AR LBD
mutation except L702H alone, bavdegalutamide showed an rPFS of 8.2
months.
"We are incredibly pleased with the results from
bavdegalutamide’s Phase 1/2 trial as they demonstrate the promise
of our AR PROTAC degraders to help patients with prostate cancer,”
said John Houston, Ph.D., chairperson, chief executive officer, and
president of Arvinas. “While bavdegalutamide’s efficacy is very
exciting, its breadth of activity could be limited to a small
patient population in a late-line setting. Our second generation
PROTAC AR degrader, ARV-766, has demonstrated a broader efficacy
profile and even better tolerability compared to bavdegalutamide in
clinical settings. Arvinas is committed to bringing forward the
best PROTAC AR degrader for patients with prostate cancer. We
believe ARV-766 has the potential to be a first- and best- in-class
treatment for patients with castrate-sensitive and
castrate-resistant prostate cancer, and we are prioritizing the
initiation of a Phase 3 clinical trial in mCRPC with ARV-766.”
Bavdegalutamide is a once-daily, oral, first-in-class PROTAC AR
degrader that degrades wild type and all clinically relevant AR LBD
mutations except AR L702H. ARV-766 was designed to improve upon the
degradation profile of bavdegalutamide by also degrading AR L702H.
The prevalence of all AR LBD mutations, especially AR L702H, has
increased over time, and these mutations are present in
approximately 25% of tumors after initial treatment with a novel
hormonal agent (NHA) such as enzalutamide or abiraterone. This
represents a potential addressable patient population for ARV-766
that is approximately three times that of bavdegalutamide in the
post-NHA population due to its broader degradation profile.
New data from the ongoing Phase 1/2 clinical trial of ARV-766
continues to show robust efficacy in tumors with all LBD mutations
(41% PSA50) and in patients with tumors harboring AR L702H
mutations (50% PSA50). In addition to a tolerability profile that
is superior to bavdegalutamide, early durability data for ARV-766
are encouraging and provide additional support for prioritizing
ARV-766 over bavdegalutamide, with PFS data anticipated in
2024.
"I’ve been involved in trials with both bavdegalutamide and
ARV-766. It’s gratifying to see these innovative therapies
developed in advanced prostate cancer where there remains a
significant need for better treatments,” said Daniel Petrylak,
M.D., Professor of Medicine and Urology at Yale School of Medicine
and investigator in the Phase 1/2 studies with bavdegalutamide and
ARV-766. “In my experience, these novel therapies have the
potential to be an important treatment choice for patients whose
tumors harbor androgen receptor LBD mutations, which may be present
in up to 25% of metastatic castration resistant prostate cancer.
The increasing prevalence of the L702H mutation means that more
patients could potentially benefit from the broader efficacy
profile offered with ARV-766. The improvement in tolerability that
ARV-766 has shown in clinical trials compared to bavdegalutamide is
also a big advantage for patients with prostate cancer.”
Highlights from the Phase 1/2 trial with
bavdegalutamide (data cut-off date Aug. 11, 2023):In a
post-NHA (median prior therapies = 4) mCRPC population,
bavdegalutamide at the recommend Phase 2 dose (420 mg, oral, once
daily) demonstrated:
- Median rPFS of 11.1 months in patients harboring AR 878/875
mutations and without co-occurring AR L702H mutations (n=26), and
median rPFS of 8.2 months in patients with tumors harboring any AR
LBD mutation except L702H alone (n=45)
- PSA50 rates of 54% in patients with tumors harboring AR 878/875
mutations and without co-occurring AR L702H, and 36% in patients
with tumors harboring any AR LBD mutation except L702H alone
- The presence of AR L702H mutations greatly diminished the
efficacy of bavdegalutamide
- In patients with any tumor harboring an AR L702H mutation, the
PSA50 was 8%
- Bavdegalutamide had a manageable tolerability profile with no
grade ≥ 4 treatment-related adverse events (TRAEs). The most
common TRAEs were grade 1 and 2 and included nausea (56%), fatigue
(35%), vomiting (33%), decreased appetite (25%) and diarrhea (24%).
The discontinuation rate due to TRAEs was 10%.
Interim data from the ongoing Phase 1/2 dose escalation
and expansion trial of ARV-766 (data cut-off date Aug. 23,
2023)Data from an updated analysis of the ongoing Phase 1/2
clinical trial demonstrate broad efficacy and excellent
tolerability in mCRPC patients with tumors harboring AR LBD
mutations, including AR L702H:
- PSA50 of 41% in patients with tumors harboring any AR LBD
mutation, and a PSA50 of 50% in patients with any tumor harboring
an AR L702H mutation
- ARV-766 was well-tolerated, with no grade ≥ 4 TRAEs. The
most common TRAEs were grade 1 or 2 and included fatigue (29%),
nausea (14%), vomiting (11%), and diarrhea (11%). The
discontinuation rate due to TRAEs was 4%.
Based on ARV-766’s superior tolerability profile and encouraging
efficacy data to date, Arvinas believes ARV-766 will be a superior
PROTAC AR degrader versus bavdegalutamide for both metastatic
castration-sensitive prostate cancer (mCSPC) and mCRPC. Arvinas
will prioritize the initiation of a Phase 3 clinical trial with
ARV-766 in mCRPC instead of the previously planned Phase 3 clinical
trial for bavdegalutamide. The Company will initiate discussions
with regulatory authorities by 2Q 2024.
Bavdegalutamide Phase 1/2 Poster
PresentationData from the Phase 1/2 trial is available
during a poster session at the 2023 European Society for Medical
Oncology (ESMO) Annual Congress in Madrid:
- Date: Sunday, October 22, 2023
- Presentation number: 1803P
- Time: 12:00 – 1:00 p.m. CEST / 6:00 – 7:00 a.m. EDT
- Speaker: Daniel Petrylak, M.D.
The Company will host a conference call and webcast call at 3:00
p.m. CEST / 9:00 a.m. EDT on October 22 to discuss these data as
well as previously undisclosed data from the ongoing Phase 1/2
clinical trial with ARV-766. Participants are invited to listen by
going to the Events and Presentation section under the Investor
page on the Arvinas website at www.arvinas.com. A replay of the
webcast will be archived on the Arvinas website following the
presentation.
About bavdegalutamide (ARV-110) and
ARV-766Bavdegalutamide (ARV-110) and ARV-766 are
investigational orally bioavailable PROTAC® protein degraders
designed to selectively target and degrade the androgen receptor
(AR). Bavdegalutamide and ARV-766 are being developed as potential
treatments for men with prostate cancer. Preclinically, both
investigational agents have demonstrated activity in models of wild
type androgen receptor tumors in addition to tumors with AR
mutations or amplification, both common potential mechanisms of
resistance to currently available AR-targeted therapies.
About ArvinasArvinas is a clinical-stage
biotechnology company dedicated to improving the lives of patients
suffering from debilitating and life-threatening diseases through
the discovery, development, and commercialization of therapies that
degrade disease-causing proteins. Arvinas uses its proprietary
PROTAC® Discovery Engine platform to engineer proteolysis targeting
chimeras, or PROTAC targeted protein degraders, that are designed
to harness the body’s own natural protein disposal system to
selectively and efficiently degrade and remove disease-causing
proteins. In addition to its robust preclinical pipeline of PROTAC
protein degraders against validated and “undruggable” targets, the
company has three investigational clinical-stage programs:
bavdegalutamide and ARV-766 for the treatment of men with
metastatic castration-resistant prostate cancer; and vepdegestrant
(ARV-471) for the treatment of patients with locally advanced or
metastatic ER+/HER2- breast cancer. For more information, visit
www.arvinas.com.
Forward-Looking Statements This press release
contains forward-looking statements within the meaning of The
Private Securities Litigation Reform Act of 1995 that involve
substantial risks and uncertainties, including statements regarding
the potential advantages and therapeutic benefits of Arvinas’
PROTAC® androgen receptor (AR) degraders, bavdegalutamide and
ARV-766; the potential for bavdegalutamide and ARV-766 as treatment
choices for patients whose tumors harbor AR ligand binding domain
mutation; the potential breadth of activity of bavdegalutamide in a
late-line setting; whether ARV-766 will be a first- and best-in
class treatment for patients with early- and late-line prostate
cancer; the addressable patient population for ARV-766,
bavdegalutamide and ARV-766 as compared to bavdegalutamide; the
timing of progression free survival data for ARV-766; whether
ARV-766 will be a superior PROTAC® AR degrader versus
bavdegalutamide for both metastatic castration-sensitive prostate
cancer and metastatic castration-resistant prostate cancer; and the
timing for Arvinas to initiate discussions with regulatory
authorities. All statements, other than statements of historical
facts, contained in this press release, including statements
regarding our strategy, future operations, future financial
position, future revenues, projected costs, prospects, plans and
objectives of management, are forward-looking statements. The words
“anticipate,” “believe,” “expect,” “intend,” “may,” “plan,”
“predict,” “target,” “potential,” “will,” “could,” “should,”
“continue,” and similar expressions are intended to identify
forward-looking statements, although not all forward-looking
statements contain these identifying words.
We may not actually achieve the plans, intentions or
expectations disclosed in our forward-looking statements, and you
should not place undue reliance on our forward-looking statements.
Actual results or events could differ materially from the plans,
intentions and expectations disclosed in the forward-looking
statements we make as a result of various risks and uncertainties,
including but not limited to: whether we will be able to
successfully conduct and complete development for ARV-766 and
bavdegalutamide; whether we initiate and complete clinical trials
for our product candidates and receive results from our clinical
trials on our expected timelines or at all; our ability to obtain
marketing approval for and commercialize our androgen receptor
program product candidates on our current timelines or at all; our
ability to maintain, expand and protect our intellectual property
portfolio; whether our cash and cash equivalent resources will be
sufficient to fund our foreseeable and unforeseeable operating
expenses and capital expenditure requirements; and other important
factors, and other important factors discussed in the “Risk
Factors” section of our Annual Report on Form 10-K for the year
ended December 31, 2022 and subsequent other reports on file with
the Securities and Exchange Commission. The forward-looking
statements contained in this press release reflect our current
views with respect to future events, and we assume no obligation to
update any forward-looking statements except as required by
applicable law. These forward-looking statements should not be
relied upon as representing our views as of any date subsequent to
the date of this release.
ContactsInvestors:Jeff Boyle+1
(347) 247-5089Jeff.Boyle@arvinas.com
Media:Kirsten Owens+1 (203)
584-0307Kirsten.Owens@arvinas.com
Grafico Azioni Arvinas (NASDAQ:ARVN)
Storico
Da Apr 2024 a Mag 2024
Grafico Azioni Arvinas (NASDAQ:ARVN)
Storico
Da Mag 2023 a Mag 2024