Clovis Oncology Receives Breakthrough Therapy Designation for Rubraca® (rucaparib) for Treatment of BRCA1/2-Mutated Metastatic Castration Resistant Prostate Cancer (mCRPC)
October 2, 2018
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Breakthrough Therapy designation (BTD) granted to Rubraca based on
initial data from ongoingTRITON2 Phase 2 study in advanced prostate
cancer -
The data set from the TRITON2 study which supported BTD will be
presented at the 2018 ESMO Congress later this month in Munich
BOULDER, Colo.–(BUSINESS WIRE)–Clovis Oncology, Inc. (NASDAQ: CLVS) announced today that the U.S. Food
and Drug Administration (FDA) has granted Breakthrough Therapy
designation for Rubraca® (rucaparib) as a monotherapy
treatment of adult patients with BRCA1/2-mutated mCRPC who have received
at least one prior androgen receptor (AR)-directed therapy and
taxane-based chemotherapy.
Breakthrough Therapy designation is granted by the FDA to
investigational agents intended to treat a serious or life-threatening
disease or condition and whose preliminary clinical evidence may
demonstrate substantial improvement on at least one clinically
significant endpoint over available therapy. The FDA previously granted
Breakthrough Therapy designation to Rubraca for the monotherapy
treatment of certain advanced ovarian cancer patients and then in
December 2016 approved Rubraca for the treatment of certain adult
patients with deleterious BRCA mutation (germline and/or somatic)
associated epithelial ovarian, fallopian tube, or primary peritoneal
cancer who have been treated with two or more chemotherapies. The FDA
subsequently approved Rubraca in a second indication, the maintenance
treatment of adult patients with recurrent epithelial ovarian, fallopian
tube, or primary peritoneal cancer who are in a complete or partial
response to platinum-based chemotherapy, in April 2018.
“We are committed to the rapid development of Rubraca in mCRPC and we
are obviously pleased to receive Breakthrough Therapy designation. We
look forward to presenting the data that served as the basis of our BTD
application at the ESMO conference later this month,” said Patrick J.
Mahaffy, President and CEO of Clovis Oncology. “We hope the decision by
the FDA to grant this Breakthrough Therapy designation for Rubraca
offers encouragement to the prostate cancer community, and we will do
our best to make Rubraca available to eligible prostate cancer patients
as quickly as possible.”
This most recent Breakthrough Therapy designation was granted to Rubraca
based on initial efficacy and safety results from TRITON2, the Phase 2
study of Rubraca in men with advanced prostate cancer with BRCA 1/2
mutations (germline or somatic) and deleterious mutations of other
homologous recombination (HR) repair genes, in the metastatic
castration-resistant setting.
Initial data from the TRITON2 clinical study, which served as the basis
for BTD, will be presented for the first time at the 2018 European
Society for Medical Oncology (ESMO) Congress taking place October 19-23,
2018, in Munich, Germany.
“We are pleased the FDA has granted Breakthrough Therapy designation to
Rubraca in mCRPC,” said Howard R. Soule, Ph.D., Executive Vice President
and Chief Scientific Officer of the Prostate Cancer Foundation. “There
is tremendous need for new therapeutic options in advanced prostate
cancer. In particular, we are enthusiastic about the potential for
targeted therapies that may provide more meaningful benefit to patients
with specific genetic mutations.”
Data from the TRITON2 clinical study will also be presented in an oral
presentation at the 25th Annual Prostate Cancer Foundation
Scientific Retreat, taking place October 26-28, 2018, in Carlsbad, CA.
About Breakthrough Therapy Designation
The Breakthrough Therapy designation was enacted as part of the 2012 FDA
Safety and Innovation Act and is intended to expedite development and
review of drugs intended to treat serious or life-threatening medical
conditions when preliminary clinical evidence demonstrates that the drug
may have substantial improvement over existing therapies on at least one
clinically significant endpoint. Breakthrough Therapy designation
includes all the features of the Fast Track designation, as well as more
intensive guidance from the FDA on a drug’s clinical development
program. The standard for breakthrough therapy designation is not the
same as the standard for drug approval and not all drugs receiving
breakthrough therapy designation will receive approval for marketing.
About Prostate Cancer
The American Cancer Society estimates that more than 164,000 men in the
United States will be diagnosed with prostate cancer in 2018, and the
GLOBOCAN Cancer Fact Sheets estimated that approximately 345,000 men in
Europe were diagnosed with prostate cancer in 2012. Castration-resistant
prostate cancer has a high likelihood of developing metastases.
Metastatic castration-resistant prostate cancer, or mCRPC, is an
incurable disease, usually associated with poor prognosis. According to
the American Cancer Society, the five-year survival rate for mCRPC is
approximately 29%. Approximately 12% of mCRPC patients have a
deleterious mutation in BRCA1 or BRCA2, according to an article
published in the Journal of Clinical Oncology in 2017. These
molecular markers may be used to select patients for treatment with a
PARP inhibitor.
About Rubraca®
Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3
being developed in multiple tumor types, including ovarian, metastatic
castration-resistant prostate, and bladder cancers, as monotherapy, and
in combination with other anti-cancer agents. Exploratory studies in
other tumor types are also underway. Clovis holds worldwide rights for
Rubraca. Rubraca is an unlicensed medical product outside of the U.S.
and Europe.
Rubraca U.S. FDA Approved Indications and Important Safety Information
Rubraca is indicated as monotherapy for the maintenance treatment of
adult patients with recurrent epithelial ovarian, fallopian tube, or
primary peritoneal cancer who are in a complete or partial response to
platinum-based chemotherapy.
Rubraca is indicated as monotherapy for the treatment of adult patients
with deleterious BRCA mutations (germline and/or somatic)
associated epithelial ovarian, fallopian tube, or primary peritoneal
cancer who have been treated with two or more chemotherapies and
selected for therapy based on an FDA-approved companion diagnostic for
Rubraca.
Select Important Safety Information
Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) occur
uncommonly in patients treated with Rubraca and are potentially fatal
adverse reactions. In approximately 1100 treated patients, MDS/AML
occurred in 12 patients (1.1%), including those in long-term follow-up.
Of these, 5 occurred during treatment or during the 28-day safety
follow-up (0.5%). The duration of Rubraca treatment prior to the
diagnosis of MDS/AML ranged from 1 month to approximately 28 months. The
cases were typical of secondary MDS/cancer therapy-related AML; in all
cases, patients had received previous platinum-containing regimens
and/or other DNA-damaging agents. Do not start Rubraca until patients
have recovered from hematological toxicity caused by previous
chemotherapy (≤ Grade 1).
Monitor complete blood counts for cytopenia at baseline and monthly
thereafter for clinically significant changes during treatment. For
prolonged hematological toxicities (> 4 weeks), interrupt Rubraca or
reduce dose (see Dosage and Administration [2.2] in full Prescribing
Information) and monitor blood counts weekly until recovery. If the
levels have not recovered to Grade 1 or less after 4 weeks, or if
MDS/AML is suspected, refer the patient to a hematologist for further
investigations, including bone marrow analysis and blood sample
cytogenetic analysis. If MDS/AML is confirmed, discontinue Rubraca.
Based on its mechanism of action and findings from animal studies,
Rubraca can cause fetal harm when administered to a pregnant woman.
Apprise pregnant women of the potential risk to a fetus. Advise females
of reproductive potential to use effective contraception during
treatment and for 6 months following the last dose of Rubraca.
Most common adverse reactions in ARIEL3 (≥ 20%; Grade 1–4) were nausea
(76%), fatigue/asthenia (73%), abdominal pain/distention (46%), rash
(43%), dysgeusia (40%), anemia (39%), AST/ALT elevation (38%),
constipation (37%), vomiting (37%), diarrhea (32%), thrombocytopenia
(29%), nasopharyngitis/upper respiratory tract infection (29%),
stomatitis (28%), decreased appetite (23%) and neutropenia (20%).
Most common laboratory abnormalities in ARIEL3 (≥ 25%; Grade 1–4) were
increase in creatinine (98%), decrease in hemoglobin (88%), increase in
cholesterol (84%), increase in alanine aminotransferase (ALT) (73%),
increase in aspartate aminotransferase (AST) (61%), decrease in
platelets (44%), decrease in leukocytes (44%), decrease in neutrophils
(38%), increase in alkaline phosphatase (37%) and decrease in
lymphocytes (29%).
Most common adverse reactions in Study 10 and ARIEL2 (≥ 20%; Grade 1–4)
were nausea (77%), asthenia/fatigue (77%), vomiting (46%), anemia (44%),
constipation (40%), dysgeusia (39%), decreased appetite (39%), diarrhea
(34%), abdominal pain (32%), dyspnea (21%) and thrombocytopenia (21%).
Most common laboratory abnormalities in Study 10 and ARIEL2 (≥ 35%;
Grade 1–4) were increase in creatinine (92%), increase in alanine
aminotransferase (ALT) (74%), increase in aspartate aminotransferase
(AST) (73%), decrease in hemoglobin (67%), decrease in lymphocytes
(45%), increase in cholesterol (40%), decrease in platelets (39%) and
decrease in absolute neutrophil count (35%).
Co-administration of Rubraca can increase the systemic exposure of
CYP1A2, CYP3A, CYP2C9, or CYP2C19 substrates, which may increase the
risk of toxicities of these drugs. Adjust dosage of CYP1A2, CYP3A,
CYP2C9, or CYP2C19 substrates, if clinically indicated. If
co-administration with warfarin (a CYP2C9 substrate) cannot be avoided,
consider increasing frequency of international normalized ratio (INR)
monitoring. Because of the potential for serious adverse reactions in
breast-fed children from Rubraca, advise lactating women not to
breastfeed during treatment with Rubraca and for 2 weeks after the last
dose. You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Clovis Oncology, Inc. at
1-844-258-7662.
Click
here for full Prescribing Information and additional Important
Safety Information.
About Clovis Oncology
Clovis Oncology, Inc. is a biopharmaceutical company focused on
acquiring, developing and commercializing innovative anti-cancer agents
in the U.S., Europe and additional international markets. Clovis
Oncology targets development programs at specific subsets of
cancer populations, and simultaneously develops, with partners,
diagnostic tools that direct a compound in development to the population
that is most likely to benefit from its use. Clovis Oncology is
headquartered in Boulder, Colorado, and has additional offices in San
Francisco and Oakland, California and Cambridge, UK. Please visit www.clovisoncology.com for
more information.
Clovis Oncology Forward-Looking Statement
To the extent that statements contained in this press release are not
descriptions of historical facts regarding Clovis Oncology, they are
forward-looking statements reflecting the current beliefs and
expectations of management. Examples of forward-looking statements
contained in this press release include, among others, statements
regarding the timing and pace of commencement of enrollment in and
completion of our clinical trials, and the potential results of such
clinical trials. Such forward-looking statements involve substantial
risks and uncertainties that could cause our future results, performance
or achievements to differ significantly from that expressed or implied
by the forward-looking statements. Such risks and uncertainties include,
among others, the uncertainties inherent in our clinical development
programs for our drug candidates and those of our partners; the timing
of availability of data from our clinical trials and the risk that final
results of trials may differ from initial or interim results; the
initiation, enrollment, timing and results of our planned clinical
trials; actions by the FDA, the EMA or other regulatory authorities
regarding whether to approve drug applications that may be filed, as
well as their decisions that may affect drug labeling, pricing and
reimbursement and other matters that could affect the availability or
commercial potential of our drug candidates. Clovis Oncology does not
undertake to update or revise any forward-looking statements. A further
description of risks and uncertainties can be found in Clovis Oncology’s
filings with the Securities and Exchange Commission, including its
Annual Report on Form 10-K and its reports on Form 10-Q and Form 8-K.
Contacts
Clovis Investor Contacts:
Anna Sussman, 303.625.5022
asussman@clovisoncology.com
or
Breanna
Burkart, 303.625.5023
bburkart@clovisoncology.com
or
Clovis
Media Contacts:
Lisa Guiterman, 301.217.9353
clovismedia@sambrown.com
or
Christy
Curran, 615.414.8668
clovismedia@sambrown.com