Market Overview

Rubraca® (rucaparib) Approved in the U.S. as Maintenance Treatment of Recurrent Ovarian Cancer

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  • Rubraca is now indicated as maintenance treatment for women with
    recurrent ovarian cancer who are in a complete or partial response to
    platinum-based chemotherapy, regardless of BRCA mutation status – no
    biomarker testing required
  • Rubraca received regular approval in this broader and earlier-line
    indication based on positive data from the phase 3 ARIEL3 clinical
    trial
  • Rubraca provided statistically-significant improvement in
    progression-free survival versus placebo in all patients studied
    (median 10.8 mos v. 5.4 mos) by investigator assessment
  • Most common Grade 3-4 adverse reaction was anemia; most common
    Grade 3-4 lab abnormality was decrease in hemoglobin

Clovis Oncology, Inc. (NASDAQ:CLVS) today announced that the U.S. Food
and Drug Administration (FDA) has approved Rubraca®
(rucaparib) tablets 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. FDA granted regular approval for Rubraca in this second,
broader and earlier-line indication on a priority review timeline based
on positive data from the phase 3 ARIEL3 clinical trial. Biomarker
testing is not required for patients to be prescribed Rubraca in this
maintenance treatment indication. Warnings and precautions include
Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), and
embryo-fetal toxicity. Please see warnings and precautions and
additional Select Important Safety Information below.

This press release features multimedia. View the full release here:
https://www.businesswire.com/news/home/20180406005678/en/

Infographic: Understanding Ovarian Cancer (Graphic: Business Wire)

Infographic: Understanding Ovarian Cancer (Graphic: Business Wire)

In addition to granting Rubraca approval in this second indication, the
FDA converted the approval of the initial treatment indication from
accelerated to regular approval.

"Rubraca provided statistically-significant improvement in PFS versus
placebo to all patients, regardless of BRCA mutation status," said
Robert L. Coleman, MD, Professor & Executive Director, Cancer Network
Research, Ann Rife Cox Chair in Gynecology, Department of Gynecologic
Oncology and Reproductive Medicine at University of Texas MD Anderson
Cancer Center in Houston and one of the Principal Investigators in the
ARIEL3 clinical trial program. "Both the efficacy and safety results
from the ARIEL3 study reinforce the important role of Rubraca in the
treatment of recurrent ovarian cancer and expands the treatment options
for patients and physicians battling this disease."

"This FDA approval provides a meaningful advancement for the treatment
of women with recurrent ovarian cancer, offering them the potential to
reduce their risk of disease progression following platinum-based
chemotherapy," said Patrick J. Mahaffy, CEO and President of Clovis
Oncology. "We are grateful that the FDA expedited review of this
maintenance treatment indication, so that physicians can begin offering
it to appropriate patients beginning today."

On February 28, 2018, Rubraca was added to the National Comprehensive
Cancer Network (NCCN) Clinical Practice Guidelines in Oncology Ovarian
Cancer, as maintenance therapy for patients with platinum-sensitive
epithelial ovarian, fallopian tube and primary peritoneal cancer who are
in partial or complete response after completion of two or more lines of
platinum-based therapy. The NCCN designated Rubraca as a category 2A
treatment.

NCCN is a not-for-profit alliance that includes 27 of the world's
leading cancer institutions. The NCCN Guidelines document
evidence-based, consensus-driven management to ensure that all patients
receive preventive, diagnostic, treatment, and supportive services that
are most likely to lead to optimal outcomes.[1]

In December 2017, FDA accepted the Rubraca supplemental New Drug
Application (sNDA) application and granted priority review status.
Priority review designation is granted to proposed medicines that FDA
has determined have the potential, if approved, to offer a significant
improvement in the safety or effectiveness for the treatment, prevention
or diagnosis of a serious condition when compared to standard
applications. The Rubraca maintenance treatment approval is based on
positive results from the ARIEL3 study, which evaluated Rubraca 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. The study enrolled a total of 564 patients.

ARIEL3 successfully achieved both its primary and key secondary
endpoints, extending investigator assessed progression-free survival
(PFS) versus placebo in all patients treated, regardless of BRCA status.

                         
Parameter Investigator Assessment
      Rubraca   Placebo
All Patientsa
Patients, N       375   189
PFS events, n (%)       234 (62%)   167 (88%)
PFS, median in months       10.8   5.4
HR (95% CI)       0.36 (0.30, 0.45)
p-value       <0.0001
tBRCA Groupb
Patients, N       130   66
PFS events, n (%)       67 (52%)   56 (85%)
PFS, median in months       16.6   5.4
HR (95% CI)       0.23 (0.16, 0.34)
p-value       <0.0001
                    a.   All randomized patients
b.

tBRCA (tumor BRCA) includes all patients with a deleterious
germline or somatic BRCA mutation, as determined by the CTA.

 

Clovis announced topline results from the ARIEL3 clinical trial in June
2017. Additional data from the trial were presented at the 2017 European
Society for Medical Oncology (ESMO) Annual Conference in Madrid, Spain,
and subsequently published in The Lancet.

"The FDA approval of Rubraca in the maintenance treatment setting is an
important milestone for physicians and their patients with recurrent
ovarian cancer because it offers them greater flexibility to use this
novel PARP inhibitor, which has demonstrated significant clinical
efficacy and has been well received in practice," said Professor
Jonathan Ledermann, MD, Professor of Medical Oncology, Clinical
Director, UCL Cancer Institute, and European and the rest of world
Principal Investigator for the ARIEL3 study. "This will enable
physicians to offer Rubraca to more women with platinum-sensitive,
recurrent ovarian cancer."

"Tens of thousands of women will battle ovarian cancer every year," said
David Barley, Chief Executive Officer, National Ovarian Cancer
Coalition. "We need therapies that provide clinically meaningful
improvements in reducing the risk of disease progression, among women
with recurrent disease."

The safety evaluation of Rubraca 600 mg twice daily as monotherapy for
maintenance treatment is based on data from 561 patients with recurrent
ovarian cancer treated in the ARIEL3 trial. The safety and tolerability
of Rubraca observed in this study was consistent with the previous
Rubraca studies. The most common adverse reactions (greater than or
equal to 20% of patients; CTCAE Grade 1-4) were nausea,
fatigue/asthenia, abdominal pain/distention, rash, dysgeusia, anemia,
AST/ALT elevation, constipation, vomiting, diarrhea, thrombocytopenia,
nasopharyngitis/upper respiratory tract infection, stomatitis, decreased
appetite and neutropenia. The most common laboratory abnormalities
(greater than or equal to 25% of patients; CTCAE Grade 1-4) were
increase in creatinine, decrease in hemoglobin, increase in cholesterol,
increase in alanine aminotransferase (ALT), increase in increase in
aspartate aminotransferase (AST), decrease in platelets, decrease in
leukocytes, decrease in neutrophils, increase in alkaline phosphatase
and decrease in lymphocytes. The majority of adverse reactions and
laboratory abnormalities were Grade 1-2.

About Rubraca Connections

Rubraca is available in the United States through specialty pharmacies
and distributors. Clovis is committed to ensuring Rubraca access for
patients and offers eligible patients financial and reimbursement
support through Rubraca Connections. More information about Rubraca
Connections is available at RubracaConnections.com or by calling
1-844-779-7707 between 8 a.m. and 8 p.m. Eastern Time, Monday through
Friday.

About Rubraca® (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3
being developed in ovarian cancer as well as several additional solid
tumor indications. Studies open for enrollment or under consideration
include ovarian, prostate, breast, gastroesophageal, pancreatic, lung
and bladder cancers. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved 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 also approved in the United
States 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.

Rubraca is an unlicensed medical product outside of the U.S.

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 ratios (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.

Please see U.S.
Prescribing Information
for 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.

This press release contains forward-looking statements (as defined
under the Private Securities Litigation Reform Act of 1995) about the
potential of Rubraca
® (rucaparib) as
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, and
reflects Clovis Oncology's current beliefs.
 As with any
pharmaceutical product, there are substantial risks and uncertainties in
the process of development and commercialization that could cause actual
results to differ materially from those expressed or implied by the
forward-looking statements. In particular, there are no guarantees that
future study results and patient experience will be consistent with the
study findings to date, that Rubraca will receive regulatory approval
for any future indications, or that it will prove to be commercially
successful. 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. All forward-looking statements are based on
information currently available to the company, and Clovis Oncology does
not undertake to update or revise any forward-looking statements

___________________________________

[1] https://www.nccn.org/about/default.aspx.
Accessed March 2018.

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