Clovis Oncology Announces First Quarter 2017 Operating Results
Strong Q1 launch quarter for Rubraca®
(rucaparib) in U.S. with
$7Mreported in net sales
- Clovis notified that ARIEL3 target progression events achieved in mid-April
- Top-line ARIEL3 data anticipated by end of June
Multiple clinical trials initiated in early 2017, including TRITON2
and TRITON3 in prostate cancer and
Roche-sponsored rucaparib-atezolizumab combination study in gynecologic cancers
- Rucaparib E.U. Marketing Authorization Application under review; establishing E.U. organization to support potential Q1 2018 European launch
“This is an exciting time at Clovis, with a robust U.S. launch of
Rubraca underway, ARIEL3 topline results expected by the end of June,
and our efforts underway to prepare for a potential E.U. launch early
next year,” said
First Quarter 2017 Financial Results
For the first time, Clovis reported a full quarter of product revenue
for Rubraca, following the approval and launch on
Clovis reported a net loss for the first quarter of 2017 of
Research and development expenses totaled
Selling, general and administrative expenses totaled
Key Milestones and Objectives for Rucaparib
ARIEL3 Timing and Regulatory Updates
Upon notification from the Independent Data Monitoring Committee in mid-April that the target number of progression events in the mutant BRCA population has been achieved, Clovis has initiated final activities in preparation for database lock and release of top-line ARIEL3 results. Top-line results from ARIEL3 are now anticipated by the end of June. Results from the trial remain blinded until the database lock occurs.
Following announcement of top-line data, Clovis plans to provide a more comprehensive presentation of the ARIEL3 results in a scientific session at a medical meeting later this year. Pending positive data, the Company intends to submit a supplemental New Drug Application (sNDA) for a second line or later maintenance treatment indication, within approximately four months after the database lock.
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 treatment to platinum-sensitive patients can extend the period of time for which the disease is controlled after a response to platinum-based chemotherapy. Patients who have high-grade serous ovarian cancer and have had at least two prior lines of platinum-based chemotherapies are randomized 2:1 to receive either rucaparib or placebo and the primary endpoint of the study is progression free survival, or PFS.
The primary efficacy analysis will evaluate, in a step-down manner, BRCA-mutant patients, all patients with a homologous recombination deficiency, or HRD, signature (including BRCA and non-BRCA), followed by all patients. In addition, a pre-specified subgroup analysis is planned to evaluate patients with low volume or no residual disease at baseline, to determine the impact of disease burden on PFS. Importantly, this analysis will also estimate the size of the population with tumor lesions greater than 2 centimeters still present after a partial response to second or later-line platinum therapy.
Pending positive results, the ARIEL3 trial is expected to serve as a
confirmatory trial for Rubraca, which was approved under the FDA’s
accelerated approval program in
The Company has an additional confirmatory study in the treatment setting, ARIEL4, which is open for enrollment. ARIEL4 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.
Clovis’ Marketing Authorization Application (MAA) for rucaparib to the
In February, Clovis entered into an agreement with Strata Oncology to accelerate patient identification and enrollment in the TRITON prostate cancer development program. The Strata trial is an observational study that provides no-cost tumor sequencing to patients at participating clinical sites, and under this agreement, match BRCA and ATM mutated advanced prostate cancer patients to Clovis’ TRITON studies. Strata has agreed not to provide similar matching services on behalf of any other Strata collaborator for any other metastatic castrate-resistant prostate cancer (mCRPC) clinical trial with respect to patients having those same genetic mutations.
In late April, Clovis and
Recent Medical Meeting Presentations
In March, new data from the ARIEL2 study of rucaparib were presented at
The integrated summary of data in patients from ARIEL2, the abstract for which was selected as the recipient of the 2017 SGO Presidential Award, analyzed objective response rate (ORR) and progression-free survival (PFS) in the 134 ovarian cancer patients with a germline or somatic BRCA mutation enrolled in ARIEL2, as well as the effect of platinum sensitivity status and prior lines of therapy on these endpoints. These data demonstrate that the objective response rate (ORR), disease control rate (DCR) and median progression-free survival (PFS) in patients with a BRCA mutation were greatest in platinum-sensitive patients, followed in descending order by those who were platinum-resistant, and those who were platinum-refractory.
This presentation also discussed the potential role of secondary somatic mutations restoring BRCA function as a mechanism of platinum resistance in patients with platinum-resistant or -refractory disease. Published data have shown that secondary mutations in BRCA are more frequently observed in platinum-resistant patients than platinum-sensitive patients. Data presented show that the presence of secondary somatic BRCA mutations may be a better predictor of rucaparib efficacy than prior responsiveness to platinum-based chemotherapy in patients with platinum-resistant or -refractory disease.
The second presentation at SGO discussed an analysis of BRCA1 and RAD51C hypermethylation among archival and pretreatment biopsies from part 1 of the ARIEL2 study. The analysis demonstrated that, among ovarian cancer patients, methylation of BRCA1 and RAD51C is associated with high loss of heterozygosity (LOH), consistent with the HRD phenotype. Further, methylation of BRCA1 and RAD51C appear to confer sensitivity to rucaparib, as do mutations of CDK12. These data suggest that methylation is more reliably assessed in pretreatment than archival tumor samples. Furthermore, analysis of baseline samples from ARIEL2 suggests that routine sequencing of high-grade ovarian cancer tumor tissue biopsies would identify at least 10-15 percent of women with a somatic mutation and 20 percent of women with a germline mutation whose tumors might be sensitive to rucaparib.
In April, rucaparib preclinical data were presented at the
The posters and presentations from SGO and AACR can be accessed at http://clovisoncology.com/pipeline/scientific-presentations/.
In addition to ARIEL3 and ARIEL4 mentioned above, 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 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.
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 bevacizumab in combination as a first-line maintenance therapy for advanced ovarian cancer, which is expected to begin enrolling patients by year-end; and
- An additional 17 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 and urothelial cancers.
Conference Call Details
Clovis will hold a conference call to discuss first quarter 2017 results
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. The 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|
|(in thousands, except per share amounts)|
|Three Months Ended March 31,|
|Product revenue, net||$||7,045||$||-|
|Cost of sales - product||1,163||-|
|Cost of sales - intangible asset amortization||372||-|
|Research and development||32,447||74,608|
|Selling, general and administrative||29,224||9,827|
|Change in fair value of contingent purchase consideration||-||516|
|Other income (expense):|
|Foreign currency losses||(159||)||(551||)|
|Other income (expense), net||(2,386||)||(2,630||)|
|Loss before income taxes||(58,547||)||(87,581||)|
|Income tax benefit||83||4,181|
|Basic and diluted net loss per common share||$||(1.33||)||$||(2.17||)|
|Basic and diluted weighted-average common shares outstanding||44,039||38,360|
|CONSOLIDATED BALANCE SHEET DATA|
|March 31, 2017||December 31, 2016|
|Cash and cash equivalents||$||276,049||$||216,186|
|Convertible senior notes||281,443||281,126|
|Common stock and additional paid-in capital||1,410,834||1,174,989|
|Total stockholders' equity (deficit)||174,209||(3,634||)|
|Three Months Ended March 31,|
|Net cash used in operating activities||(80,439||)||$||(83,738||)|
|Share Based Compensation Expense||8,947||$||10,965|