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Clovis Oncology Submits Application to EMA to Expand Use of Rubraca®▼ (rucaparib) to Include Maintenance Treatment for Women with Recurrent Ovarian Cancer

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  • Submission based on positive phase 3 ARIEL3 clinical trial in
    which rucaparib significantly improved PFS in all primary efficacy
    ovarian cancer patient populations studied
  • Timing of maintenance treatment application submission to EMA
    may allow for a CHMP opinion by year-end 2018

Clovis Oncology, Inc. (NASDAQ:CLVS) today announced the submission of a
regulatory application to the European Medicines Agency (EMA), as part
of a type II variation seeking to expand the marketing authorization for
Rubraca (rucaparib) to include 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.

On May 29, 2018, Rubraca became the first PARP inhibitor licensed in the
EU as a monotherapy treatment for women with recurrent ovarian cancer.
It is currently 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 platinum
based chemotherapy. The Rubraca Summary of Product Characteristics is
available on the European Medicines Agency website.

This submission is based on the positive results from the phase 3 ARIEL3
study, which evaluated rucaparib in the ovarian cancer maintenance
treatment setting among three populations: 1) BRCA mutant (BRCAmut+) 2)
HRD positive inclusive of BRCAmut+ and, 3) all patients treated in
ARIEL3. ARIEL3 successfully achieved its primary endpoints, extending
investigator assessed progression-free survival (PFS) versus placebo in
all patients treated, regardless of BRCA status. Safety findings from
the ARIEL3 trial were consistent with previous clinical trials.

Based on the timing of this submission, the company anticipates an
opinion from the Committee for Medicinal Products for Human Use (CHMP)
by end of 2018.

About the ARIEL3 Clinical Trial

The ARIEL3 pivotal study of rucaparib is a confirmatory randomized,
double-blind study comparing the effects of rucaparib against placebo to
evaluate whether rucaparib given as a maintenance treatment to
platinum-sensitive ovarian cancer patients can extend the period of time
for which the disease is controlled after a complete or partial response
to platinum-based chemotherapy. The study enrolled 564 patients with
high-grade epithelial ovarian, fallopian tube or primary peritoneal
cancer. To be eligible for the study, participants had to have received
at least two prior platinum-based treatment regimens, been sensitive to
the penultimate platinum regimen, and achieved a complete or partial
response to their most recent platinum-based regimen. There were no
genomic selection criteria for this study. Trial participants were
randomized 2:1 to receive 600 milligrams of rucaparib twice daily (BID)
or placebo.

About Rubraca® (rucaparib)

Rucaparib 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
rucaparib. Rucaparib is an unlicensed medical product outside of the
U.S. and Europe.

Rubraca EU Authorized Use

Rucaparib is licensed 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.

Click
here
to access the current Summary of Product Characteristics.
Healthcare professionals should report any suspected adverse reactions
via their national reporting systems.

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 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
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 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)
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 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, 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 made pursuant to the safe harbor provisions
of the Private Securities Litigation Reform Act of 1995. Examples of
forward-looking statements contained in this press release include,
among others, statements regarding our expectation of timing for review
and approval of the variation seeking to expand the marketing
authorization for Rubraca
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 regulatory matters,
including actions by regulatory authorities regarding whether to approve
drug applications that may be filed, as well as their decisions that may
affect drug labeling 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.

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