- Seeking approval for mutant BRCA
patients treated with two or more prior therapies
- FDA Grants Priority Review Status
- Assigns PDUFA Date of February 23,
2017
Clovis Oncology, Inc. (NASDAQ: CLVS) announced today that the
U.S. Food and Drug Administration (FDA) has accepted Clovis’ New
Drug Application (NDA) for accelerated approval of rucaparib and
granted priority review status to the application with a
Prescription Drug User Fee Act (PDUFA) date of February 23, 2017.
In late June 2016, Clovis completed its NDA submission of rucaparib
to the FDA for the treatment of advanced ovarian cancer in patients
with deleterious BRCA-mutated tumors inclusive of both germline and
somatic BRCA mutations (as detected by an FDA-approved test), and
who have been treated with two or more chemotherapies. Rucaparib
was granted Breakthrough Therapy Designation for the proposed
indication by the FDA in April 2015.
“The acceptance of the rucaparib NDA submission represents an
important milestone for rucaparib, and for Clovis,” said Patrick J.
Mahaffy, President and CEO of Clovis Oncology. “There is tremendous
need for additional therapeutic options for patients with advanced
mutant BRCA ovarian cancer and we look forward to cooperating with
FDA on the rucaparib NDA review.”
“Recurrent ovarian cancer remains a very difficult disease to
treat, even among women who carry, or whose tumors have a mutation
in the BRCA genes. Despite the available treatment options, few
effective therapies are at our disposal. Thus, the opportunity to
treat women with germline or somatic BRCA mutations with rucaparib
after two prior lines of platinum-based therapy, represents a
meaningful step forward for our patients,” said Robert L. Coleman,
MD, Professor & Deputy Chairman, Vice Chair, Clinical 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 ARIEL clinical trial program.
Foundation Medicine, Clovis’ companion diagnostic partner, has
submitted a Premarket Approval (PMA) application for its
FoundationFocus CDxBRCA to the FDA in June 2016. The test is
designed to identify tumor BRCA mutations, including germline and
somatic BRCA mutations. The timing of the submission is expected to
allow for regulatory approval of the companion diagnostic in a
similar timeframe.
About the Submission: Efficacy
The efficacy of rucaparib was assessed in 106 patients from two
multicenter, single-arm, open-label clinical trials, Study 1 (Study
10, NCT01482715) and Study 2 (ARIEL2 Parts 1 and 2, NCT01891344),
in patients with advanced BRCA-mutant ovarian cancer who had
progressed after two or more prior chemotherapies. Median age was
59 years and median number of prior chemotherapy regimens was
three.
Study 1 was limited to platinum sensitive patients; Study 2
included platinum sensitive, platinum resistant and platinum
refractory patients.
All 106 patients received the starting dose of rucaparib 600 mg
twice daily. The major efficacy outcome measure of both trials was
objective response rate (ORR) and duration of response (DOR) as
assessed by the investigator according to Response Evaluation
Criteria in Solid Tumors (RECIST) version 1.1. All responses were
confirmed.
Efficacy results from Study 1 and Study 2 in all patients
treated are summarized in the table below:
Overall Response and Duration of Response in Patients with
BRCA-mutant Ovarian Cancer Who Received 2 or More Chemotherapies in
Study 1 and Study 2
Activity by RECIST 1.1 per Investigator
Assessment
Study 1
N=42
Study 2
N=64
Overall1
N=106
Objective Response Rate (95% CI) 60% (43, 74)
50% (37, 63) 54% (44, 64)
Complete Response 10% 8%
9% Partial Response 50%
42% 45%
Median Duration of Response in months (95%
CI)
7.8 (5.6, 10.5) 11.6
(5.5, 18.2) 9.2 (6.6, 11.6)
1 Pooled analysis of Study 1 and Study 2Confidence Interval
(CI)
Nine (9%) of the 106 patients overall had progressive disease as
best response. The ORR was similar for patients with germline
BRCA-mutant ovarian cancer or somatic BRCA-mutant ovarian cancer
and for patients with a BRCA1 gene mutation or BRCA2 gene
mutation.
About the Submission: Safety
The safety population is comprised of the 377 ovarian cancer
patients treated with starting dose of rucaparib 600 mg twice daily
in Study 1 and Study 2.
The Grade 3/4 treatment emergent adverse events (AEs) reported
in ≥10% of patients were anemia/decreased or low hemoglobin (25%),
fatigue/asthenia (11%) and increased ALT/AST (11%).
The increases in aspartate (AST) and alanine (ALT)
aminotransferase levels that were observed were asymptomatic,
reversible and were rarely associated with increases in bilirubin.
The elevations normalized over time with continued rucaparib
treatment.
The discontinuation rate for ovarian cancer patients due to
rucaparib-related AEs was 8%.
Myelodysplastic syndrome (MDS) was reported in 1 of 377 (0.3%)
patients with ovarian cancer.
In addition, in the ongoing ARIEL3 maintenance trial, a blinded,
randomized trial evaluating rucaparib versus placebo, acute myeloid
leukemia (AML) was reported in 2 (<0.5%) patients with ovarian
cancer. One case of AML was fatal. Both of these patients had
received prior treatment with platinum and other DNA damaging
agents.
About Rucaparib
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2
and PARP3 being developed for advanced ovarian cancer.
Specifically, rucaparib is being developed as monotherapy
treatment of advanced ovarian cancer in patients with deleterious
BRCA-mutated tumors inclusive of both germline and somatic BRCA
mutations (as detected by an FDA-approved test) who have been
treated with two or more chemotherapies. Rucaparib was granted
Breakthrough Therapy Designation for this proposed indication by
the U.S. FDA in April 2015; and in late June 2016, Clovis completed
its New Drug Application (NDA) submission to the FDA. The filing
for treatment was accepted and has an action date of February 23,
2017. Rucaparib’s Marketing Authorization Application (MAA) to the
European Medicines Agency for the proposed treatment indication is
planned for Q4 2016.
Additionally, rucaparib is being developed as maintenance
therapy in the ARIEL3 trial (NCT01968213) for patients with tumors
with BRCA mutations and other DNA repair deficiencies beyond BRCA
(commonly referred to as homologous recombination deficiencies, or
HRD). Data from ARIEL3 are expected in Q4 2017, which is expected
to be followed by the submission of a supplemental NDA for
second-line maintenance therapy.
Clovis is also exploring rucaparib in other solid tumor types
with BRCA and HRD populations, including prostate, breast and
gastroesophageal cancers.
Clovis holds worldwide rights for rucaparib.
About Rucaparib Clinical Development in Ovarian
Cancer
The ARIEL (Assessment of Rucaparib in Ovarian Cancer Trial)
program is a novel, integrated translational-clinical program
designed to accurately and prospectively identify ovarian cancer
patients with tumor genotypes associated with benefit from
rucaparib therapy.
- ARIEL2 is a two-part single-arm open
label study designed to identify pre-specified tumor
characteristics that predict sensitivity to rucaparib using DNA
sequencing to evaluate each patient’s tumor. Part 1 enrolled 204
platinum-sensitive patients and updated results were presented in
June 2016. Part 2 enrolled 286 patients with advanced ovarian
cancer who have received at least three prior chemotherapy regimens
and includes platinum-sensitive, -resistant and -refractory
patients. ARIEL2 is evaluating clinical response in patients
classified into molecularly-defined subgroups, including germline
BRCA-mutant, somatic BRCA-mutant and HRD by a prospectively defined
genomic signature.
- The phase 2 portion of Study 10, the
initial dose finding study, enrolled patients with relapsed,
high-grade ovarian cancer associated with a deleterious germline
BRCA mutation who received 2-4 prior lines of chemotherapy.
- The ARIEL3 pivotal study is a
randomized, double-blind study comparing the effects of rucaparib
against placebo to evaluate whether rucaparib given as a
maintenance therapy to platinum-sensitive patients can extend the
period of time for which the disease is controlled after a positive
outcome with platinum-based chemotherapy. Patients are randomized
to receive either placebo or rucaparib and the primary endpoint of
the study is PFS. The primary efficacy analysis will evaluate, in a
step-down process, BRCA-mutant patients, all patients with a HRD
signature (including BRCA and non-BRCA), followed by all patients.
Target enrollment in ARIEL3 was completed during the second quarter
of 2016.
- The ARIEL4 confirmatory study (NCT
02855944), expected to begin during the second half of 2016, is a
Phase 3 multicenter, randomized study of rucaparib versus
chemotherapy in relapsed ovarian cancer patients with BRCA
mutations who have failed two prior lines of therapy. The primary
endpoint of the study is PFS.
- For more information, please visit
www.arielstudy.com.
In addition to the ARIEL program in ovarian cancer, the Company
is exploring rucaparib in other solid tumor types with BRCA and HRD
populations, including two monotherapy prostate cancer studies as
well as multiple combination studies, including with inhibitors of
PD-L1, are planned to initiate in late 2016 and early 2017.
An abstract based on the ovarian NDA dataset has been accepted
for an oral presentation at the ESMO 2016 Congress in October
2016.
About Ovarian Cancer
According to the American Cancer Society, more than 22,000 women
will be diagnosed with ovarian cancer in the U.S. during 2016.
There are often no clearly identifiable initial symptoms, and in an
estimated 80 to 85% of ovarian cancer cases, the cancer has spread
to other parts of the body before a person is diagnosed and can be
treated. Ovarian cancer ranks fifth in cancer deaths and causes
more deaths than any other cancer of the female reproductive
system. One in four women with ovarian cancer have a germline or
somatic BRCA mutation, and new treatment options are needed to
treat unique patient populations.
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 aimed at specific
subsets of cancer populations, and simultaneously develops
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.
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.
Such forward-looking statements involve substantial risks and
uncertainties that could cause our clinical development programs,
future results, performance or achievements to differ significantly
from those 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, the corresponding development pathways of our
companion diagnostics, 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
regarding drug labeling, and other matters that could affect the
availability or commercial potential of our drug candidates or
companion diagnostics, including competitive developments. 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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version on businesswire.com: http://www.businesswire.com/news/home/20160823006191/en/
Clovis Oncology, Inc.Breanna Burkart,
303-625-5023bburkart@clovisoncology.comorAnna Sussman,
303-625-5022asussman@clovisoncology.com
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