- European Commission (EC) marketing authorization is anticipated Q1
- Upon receipt of marketing authorization by the EC, Rubraca will
offer a new monotherapy option for the maintenance treatment of adults
with platinum-sensitive relapsed high-grade epithelial ovarian,
fallopian tube, or primary peritoneal cancer who are in response
(complete or partial) to platinum-based chemotherapy
BOULDER, Colo. -- (Business Wire)
Clovis Oncology, Inc. (NASDAQ: CLVS) today announced that the European
Union’s (EU) European Medicines Agency (EMA) Committee for Medicinal
Products for Human Use (CHMP) has adopted a positive opinion
recommending an additional indication to include rucaparib as
monotherapy for the maintenance treatment of adult patients with
platinum-sensitive relapsed high-grade epithelial ovarian, fallopian
tube, or primary peritoneal cancer who are in response (complete or
partial) to platinum-based chemotherapy. EC approval is anticipated in
the first quarter of 2019.
Once approved, Rubraca’s indication will expand beyond its initial
Marketing Authorization in Europe granted in May 2018 for adult patients
with platinum-sensitive, relapsed or progressive, BRCA mutated (germline
and/or somatic), high-grade epithelial ovarian, fallopian tube, or
primary peritoneal cancer, who have been treated with two or more prior
lines of platinum-based chemotherapy, and who are unable to tolerate
further platinum-based chemotherapy.
The CHMP’s positive opinion for this additional indication was based on
data from the phase 3 ARIEL3 clinical trial, which found that rucaparib
significantly improved progression-free survival in all ovarian cancer
patient populations studied.i
“The CHMP recommendation represents an important step forward for women
with recurrent ovarian cancer, for whom additional treatment options are
needed. The ARIEL3 trial demonstrated rucaparib to be effective across
all patient types, regardless of their BRCA mutation status, and is the
only PARP-inhibitor trial in which independent radiological review
reported a median progression-free survival of more than one year across
the entire population studied,” said Professor Jonathan Ledermann, MD,
Professor of Medical Oncology, UCL Cancer Institute and UCL Hospitals,
London, global Principal Investigator for non-US sites in the ARIEL3
study. “The meaningful efficacy data and tolerable safety profile offers
women diagnosed with relapsed ovarian cancer a new therapy option.”
Ovarian cancer is the sixth deadliest cancer amongst women in Europe,
where more than 65,000 women are diagnosed annually.ii
Ovarian cancer is challenging to treat, and most women will relapse
after surgery and chemotherapy. The 80 to 85 percent of women diagnosed
in the later stages of the disease (III and IV) have particularly poor
“We are pleased that the CHMP recognizes the clinical relevance of
rucaparib in the maintenance treatment setting for European women with
relapsed platinum-sensitive ovarian cancer,” said Patrick J. Mahaffy,
President and CEO of Clovis Oncology. “This brings us a step closer to
delivering on our commitment to ensure that women who may benefit from
treatment with rucaparib have the opportunity to do so. We seek to make
ovarian cancer an actively managed disease, rather than one that is
treated and then wait for recurrence. Rucaparib’s clinical benefit in
the maintenance treatment setting is supported by the pivotal ARIEL3
study, which showed that Rubraca provided benefit in all ovarian cancer
patient populations studied.”
About the ARIEL3 Pivotal Study
ARIEL3 is a double-blind, placebo-controlled trial of rucaparib that
enrolled 564 women with platinum-sensitive, high-grade ovarian,
fallopian tube, or primary peritoneal cancer. The primary efficacy
analysis evaluated three prospectively defined molecular sub-groups in a
step-down manner: 1) BRCA mutant (BRCAmut+); 2) HRD positive (HRD+)
inclusive of BRCA mutant; and finally, 3) the intent-to-treat
population, or all patients treated in ARIEL3. The study achieved its
primary endpoint of improved PFS by investigator review in each of three
About Rubraca® (rucaparib)
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.
In October 2018, Rubraca was granted Breakthrough Therapy Designation by
the FDA as 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.
Clovis holds worldwide rights for Rubraca. Rubraca is an unlicensed
medical product outside of the U.S. and Europe.
Rucaparib EU Authorized Use
Rucaparib is indicated for adult patients with platinum sensitive,
relapsed or progressive, BRCA mutated (germline and/or somatic),
high-grade epithelial ovarian, fallopian tube, or primary peritoneal
cancer, who have been treated with two or more prior lines of
platinum-based chemotherapy, and who are unable to tolerate further
here to access the current Summary of Product Characteristics.
Healthcare professionals should report any suspected adverse reactions
via their national reporting systems.
Rucaparib U.S. FDA Approved Indications and Important Safety
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
Rubraca is indicated as monotherapy for the treatment of 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 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 for
cytogenetics. 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
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 rucaparib 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)
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
here for full Prescribing Information and additional Important
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 intended to 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 clovisoncology.com
for more information.
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 our expectation of timing for European Commission approval of
rucaparib for the maintenance treatment indication. 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 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 or companion diagnostics.
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.
i Coleman RL et al. Rucaparib maintenance treatment for
recurrent ovarian carcinoma after response to platinum therapy (ARIEL3):
a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet
ii World Health Organization.
Globocan 2012: estimated cancer incidence, mortality and prevalence
worldwide in 2012. Accessed 23 February 2018.
American Cancer Society. Survival rates for ovarian cancer, by stage. https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html
View source version on businesswire.com: https://www.businesswire.com/news/home/20181213005680/en/
Clovis Investor Contacts:
Anna Sussman, 303.625.5022
Lisa Guiterman, 301.217.9353
Hughes, +44 (0) 7956 700 790
Source: Clovis Oncology, Inc.
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