Clovis Oncology Receives Breakthrough Therapy Designation for Rubraca®
(rucaparib) for Treatment of BRCA1/2-Mutated Metastatic Castration Resistant Prostate Cancer (mCRPC)
- 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
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.
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
View source version on businesswire.com: https://www.businesswire.com/news/home/20181002005512/en/