Clovis Oncology Announces Second Quarter 2017 Operating Results
- Strong second quarter of launch for Rubraca®
(rucaparib) in U.S. with
$14.6Mreported in net sales
- Positive topline data from the ARIEL3 study reported on
June 19, 2017; presentation of full dataset confirmed at European Society for Medical Oncology2017 Congressin Madrid
- Clovis plans to submit a supplemental New Drug Application (sNDA) for a second-line and later maintenance treatment indication before the end of October
- Rucaparib E.U. Marketing Authorization Application under review; establishing E.U. organization to support a potential European launch
- Broad clinical collaboration with
Bristol-Myers Squibbto evaluate Rubraca in combination with Opdivo® (nivolumab) in several late-stage clinical trials in multiple tumor types; studies are expected to begin before the end of 2017
“This is clearly an exciting time for our company, for PARP inhibitors
generally, and for Rubraca specifically,” said
Second Quarter 2017 Financial Results
Following the approval and launch of Rubraca on
Clovis reported a net loss for the second quarter of 2017 of
Research and development expenses totaled
Selling, general and administrative expenses totaled
New Clinical Collaboration with
Earlier in the week, Clovis and
ARIEL3 Topline Results
ARIEL3 is a double-blind, placebo-controlled, phase 3 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) tumor BRCA mutant (tBRCAmut) patients, inclusive of germline and somatic mutations of BRCA; 2) HRD-positive patients, including BRCA-mutant patients and BRCA wild-type with high loss of heterozygosity, or LOH-high patients; and, finally, 3) the intent-to-treat population, or all patients treated in ARIEL3.
Following is a table and a summary of the primary efficacy analyses and selected exploratory PFS endpoints per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by each of investigator review, which was the primary analysis of ARIEL3, and independent review (BICR), a key secondary endpoint of the study.
Summary of Primary Efficacy Analyses and Selected Exploratory Endpoints for ARIEL3
PFS by Investigator Review
PFS by Blinded Independent Central Review
Median PFS (months)
Median PFS (months)
|16.6 vs. 5.4||
|26.8 vs. 5.4|
|13.6 vs. 5.4||
|22.9 vs. 5.5|
|10.8 vs. 5.4||
|13.7 vs. 5.4|
BRCAwt / HRD-positive
|9.7 vs. 5.4||0.55; p=0.0135||11.1 vs. 5.6|
BRCAwt / HRD-negative
|0.58; p=0.0049||6.7 vs. 5.4||0.47; p=0.0003||8.2 vs. 5.3|
PFS: progression-free survival; tBRCAmut: tumor BRCA mutant; HRD: homologous recombination deficiency; BRCAwt: BRCA wild type
Exploratory Endpoint of Response Rate
Enrollment in ARIEL3 included one-third of patients who had achieved a complete response to their prior platinum-based therapy, and two-thirds of patients who had achieved a partial response to their prior platinum-based therapy. Of those with a partial response, 37% had measurable disease at the time of enrollment and were therefore evaluable for response. The confirmed overall response rate by investigator-assessed RECISTv1.1 in the tBRCAmut group treated with rucaparib was 38% (15/40); of these, 18% (7/40) were complete responses. This compared with 9% (2/23) in the placebo group (p=0.0055). No complete responses were seen in the tBRCAmut placebo group. RECIST responses were also observed in BRCA wild type HRD positive and BRCA wild type HRD negative subgroups.
RECIST responses were not assessed by independent blinded review.
Summary of ARIEL3 Safety
The most common (≥5%) treatment-emergent grade 3/4 adverse events (TEAEs) among all patients treated with rucaparib in the ARIEL3 study were anemia/decreased hemoglobin (19%), ALT/AST increase (11%), asthenia/fatigue (7%), neutropenia (7%), and thrombocytopenia (5%).The discontinuation rate for TEAEs was 14% for rucaparib-treated patients and 2.6% for the placebo arm. The rate of treatment-emergent myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) in the rucaparib arm was <1% (3/372), and no patients on the placebo arm experienced treatment-emergent MDS/AML.
The ARIEL3 data has been accepted at the
Rucaparib Regulatory Update
Based on the ARIEL3 dataset, the Company plans to submit a supplemental New Drug Application (sNDA) by the end of October for a second-line and later maintenance treatment indication for all women with platinum-sensitive ovarian cancer who have responded to their most recent platinum therapy.
Clovis’ Marketing Authorization Application (MAA) for rucaparib to the
Clovis has a robust clinical development program underway in multiple tumor types, including both Clovis-sponsored and investigator-initiated trials. The following clinical studies are open for enrollment or are anticipated to open during 2017:
- The Clovis-sponsored ARIEL4 confirmatory study in the treatment setting is a Phase 3 multicenter, randomized study of rucaparib versus chemotherapy in relapsed ovarian cancer patients with BRCA mutations (inclusive of germline and/or somatic) who have failed two prior lines of therapy. The primary endpoint of the study is PFS. This study is currently enrolling patients.
- The Clovis-sponsored TRITON2 (Trial of Rucaparib in Prostate Indications) study in mCRPC, a Phase 2 single-arm study enrolling patients with BRCA mutations and ATM mutations (both inclusive of germline and somatic) or other deleterious mutations in other homologous recombination (HR) repair genes and all patients will have progressed after receiving one line of taxane-based chemotherapy and one or two lines of androgen-receptor (AR) targeted therapy. This study is currently enrolling patients.
- The Clovis-sponsored TRITON3 study, a Phase 3 comparative study in mCRPC enrolling BRCA mutant and ATM mutant (both inclusive of germline and somatic) patients who have progressed on AR-targeted therapy and who have not yet received chemotherapy in the castrate-resistant setting is also open for enrollment. TRITON3 will compare rucaparib to physician’s choice of AR-targeted therapy or chemotherapy in these patients. This study is currently enrolling patients.
A Clovis-sponsored Phase 3 study in advanced ovarian cancer in the
first-line maintenance treatment setting evaluating rucaparib plus the
cancer immunotherapy Opdivo (nivolumab; anti-PD1), rucaparib, Opdivo
and placebo in newly-diagnosed patients who have completed
platinum-based chemotherapy. This study, as part of a broad clinical
Bristol-Myers Squibb, is expected to begin before the end of 2017.
The Phase 3 combination study of the cancer immunotherapy Opdivo plus
rucaparib for the treatment of advanced triple-negative breast cancers
(TNBC) associated with homologous recombination deficiency (HRD). This
study is sponsored by
Bristol-Myers Squibband is expected to begin before the end of 2017.
The Phase 2 combination study of the cancer immunotherapy Opdivo plus
rucaparib for the treatment of mCRPC. This study, sponsored by
Bristol-Myers Squibb, will be conducted as an arm of a larger Bristol-Myers Squibb-sponsored prostate cancer study. This study is expected to begin before the end of 2017.
The Phase 1b combination study of the cancer immunotherapy Tecentriq
(atezolizumab; anti-PDL1) and rucaparib for the treatment of
gynecological cancers, with a focus on ovarian cancer. This study is
Rocheand is currently enrolling patients.
- The cooperative group-sponsored MITO-25 study evaluating rucaparib and the anti-angiogenic therapy, bevacizumab, in combination as a first-line maintenance therapy for advanced ovarian cancer, which is expected to begin enrolling patients by year-end; and
- Additional investigator-initiated or cooperative group-initiated studies of rucaparib as single-agent or in combination therapy are underway or planned, including studies in ovarian, prostate, breast, gastroesophageal, pancreatic, lung, bladder and urothelial cancers.
Conference Call Details
Clovis will hold a conference call to discuss second quarter 2017
About Rubraca® (rucaparib)
Rubraca is a PARP inhibitor indicated as monotherapy for the treatment
of patients with deleterious BRCA mutation (germline and/or
somatic) associated advanced ovarian cancer, who have been treated with
two or more chemotherapies, and selected for therapy based on an
Rucaparib is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3
being developed in ovarian cancer as well as several additional solid
tumor indications. During the fourth quarter of 2016, the Marketing
Authorization Application (MAA) submission in
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 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 the market potential of our approved drug, including the performance of our sales and marketing efforts and the success of competing drugs, the performance of our third-party manufacturers, our clinical development programs for our drug candidates, the corresponding development pathways of our companion diagnostics, the timing of availability of data from our clinical trials and the results, the initiation, enrollment and timing 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 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.
|CLOVIS ONCOLOGY, INC|
|CONSOLIDATED FINANCIAL RESULTS|
|(Unaudited, in thousands, except per share amounts)|
|Three Months Ended June 30,||Six Months Ended June 30,|
|Product revenue, net||$||14,620||$||-||$||21,665||$||-|
|Cost of sales - product||2,730||-||3,893||-|
|Cost of sales - intangible asset amortization||372||-||743||-|
|Research and development||33,108||67,729||65,555||142,337|
|Selling, general and administrative||36,149||9,552||65,373||19,379|
|Acquired in-process research and development||-||300||-||300|
|Impairment of intangible asset||-||104,517||-||104,517|
|Change in fair value of contingent purchase consideration||-||(25,452||)||-||(24,936||)|
|Other income (expense):|
|Foreign currency gain (loss)||76||183||(83||)||(368||)|
|Legal settlement loss||(117,000||)||-||(117,000||)||-|
|Other income (expense), net||(118,928||)||(1,727||)||(121,315||)||(4,357||)|
|Loss before income taxes||(176,667||)||(158,373||)||(235,214||)||(245,954||)|
|Income tax benefit||1,281||29,059||1,365||33,240|
|Basic and diluted net loss per common share||$||(3.88||)||$||(3.37||)||$||(5.24||)||$||(5.54||)|
|Basic and diluted weighted-average common shares outstanding||45,176||38,389||44,610||38,375|
|RECONCILIATION OF GAAP TO NON-GAAP|
|NET LOSS AND NET LOSS PER SHARE|
|(Unaudited, in thousands, except per share amounts)|
|Three Months Ended June 30,||Six Months Ended June 30,|
|GAAP net loss||$||(175,386||)||$||(129,314||)||$||(233,849||)||$||(212,714||)|
|Legal settlement loss (1)||117,000||-||117,000||-|
|Impairment of intangible asset (2)||104,517||104,517|
|Change in fair value of contingent purchase consideration (3)||(25,452||)||(25,452||)|
|Income tax benefit (2)||(29,160||)||(29,160||)|
|Non-GAAP net loss||$||(58,386||)||$||(79,409||)||$||(116,849||)||$||(162,809||)|
|GAAP net loss per common share||$||(3.88||)||$||(3.37||)||$||(5.24||)||$||(5.54||)|
|Non-GAAP net loss per common share||$||(1.29||)||$||(2.07||)||$||(2.62||)||$||(4.24||)|
The Company prepares its consolidated financial statements in accordance with U.S. GAAP. This press release also contains non-GAAP measurements of net loss and net loss per common share that the Company believes provide useful supplemental information relating to operating performance and trends and facilitates comparisons with other periods. These non-GAAP financial measures should be considered in addition to, but not as a substitute for, the information prepared in accordance with U.S. GAAP.
Explanation of adjustments:
|(1)||During the three months ended June 30, 2017, the Company recorded a $117.0 million legal settlement loss related to a stipulation and agreement of settlement entered into between the Clovis Defendants and the plaintiffs to the Consolidated Complaint.|
During the three months ended June 30, 2016, the Company recorded a $104.5 million non-cash impairment charge to the intangible asset related to the lucitanib product rights initially recorded in 2013 in connection with the acquisition of Ethical Oncology Science, S.p.A. (EOS). The Company also recorded a $29.2 million tax benefit associated with this charge. This adjustment removes the net of tax effect of this charge from our net loss.
|(3)||During the three months ended June 30, 2016, the Company recorded a $25.5 million non-cash credit to operating expenses to reflect the reduction in the fair value of the contingent purchase consideration liability, also associated with the Company's acquisition of EOS. This adjustment, which excludes the normal accretion of the liability, removes the effect of this expense credit from our net loss.|
|CONSOLIDATED BALANCE SHEET DATA|
|June 30, 2017||December 31, 2016|
|Cash and cash equivalents||$||491,786||$||216,186|
|Convertible senior notes||281,761||281,126|
|Common stock and additional paid-in capital||1,752,992||1,174,989|
|Total stockholders' equity (deficit)||343,793||(3,634||)|
|(Unaudited, in thousands)|
|Six Months Ended June 30,|
|Net cash used in operating activities||(149,541||)||$||(151,670||)|
|Share Based Compensation Expense||19,563||$||20,542|