On February 22, 2017 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter and year ended December 31, 2016, and provided an update on the Company’s clinical development programs and regulatory outlook for 2017 (Press release, Clovis Oncology, FEB 22, 2017, View Source;p=RssLanding&cat=news&id=2248380 [SID1234517803]).
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"We are extremely pleased with the Rubraca launch to date; our commercial team hit the ground running and we are committed to the successful launch of this new therapeutic option for the treatment of advanced ovarian cancer," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "We are preparing for a potential approval in the EU in late 2017 or early 2018, and are aggressively building our European organization. We continue to anticipate the ARIEL3 read out in mid-2017, and we look forward to expanding the TRITON program into earlier line castrate-resistant prostate cancer. We will provide additional details on this study and other clinical development plans to develop rucaparib in other indications as well as in combination with an immuno-oncology agent over the course of this year."
Fourth Quarter and Year-End 2016 Financial Results
Clovis had $266.2 million in cash, cash equivalents and available-for-sale securities as of December 31, 2016. Cash used in operating activities was $54.7 million for the fourth quarter of 2016 and $266.7 million for the year ended December 31, 2016. Clovis had approximately 38.7 million shares of common stock outstanding as of December 31, 2016. In January 2017, the Company raised net proceeds of $221.2 million through an offering of 5.75 million shares of common stock.
Clovis reported a net loss for the fourth quarter of 2016 of $70.7 million, or ($1.83) per share, and $349.1 million or ($9.07) per share for the year ended December 31, 2016. The net loss for the fourth quarter of 2015 was $119.5 million or ($3.12) per share and $352.9 million or ($9.79) per share for the year ended December 31, 2015. Net loss for the fourth quarter of 2016 included share-based compensation expense of $10.1 million and $39.8 million for the full year 2016, respectively, compared to $10.9 million and $40.4 million for the comparable periods of 2015. Net product revenue for the quarter and the year was $78 thousand, following the approval and launch of Rubraca on December 19, 2016.
The net loss for the year ended December 31, 2016 includes a net expense non-cash impact of $50.6 million relating to the lucitanib product rights recorded in 2013 in connection with the Company’s acquisition of Ethical Oncology Science S.p.A. (EOS), comprised of a $104.5 million non-cash expense for the impairment of the intangible asset, a $25.5 million non-cash expense credit for the reduction in the fair value of the contingent purchase consideration liability and a $28.4 million related non-cash income tax benefit. The non-GAAP adjusted net loss excluding these items was $298.6 million or ($7.76) per share for the full year 2016.
Research and development expenses totaled $54.5 million for the fourth quarter of 2016, and $251.1 million for the full year 2016, compared to $76.0 million and $269.3 million, respectively, for the comparable periods in 2015. The decrease year over year is primarily due to decreased development activities for the rociletinib program and to a lesser extent, expenses related to the commercialization of Rubraca, which had been classified as research and development prior to FDA approval, partially offset by higher expenses related to the rucaparib program.
Selling, general and administrative expenses totaled $12.2 million for the fourth quarter of 2016, and $40.7 million for the full year 2016, compared to $8.2 million and $30.5 million for the comparable periods in 2015. The increase year over year is primarily due to higher legal costs; selling, general and administrative expenses related to the commercialization of Rubraca, which had been classified as research and development prior to FDA approval; and to a lesser extent, higher personnel costs.
Key Milestones and Objectives for Rucaparib
On December 19, 2016, the U.S. Food and Drug Administration (FDA) approved Rubraca (rucaparib) tablets 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 FDA-approved companion diagnostic for Rubraca. The indication for Rubraca is approved under the FDA’s accelerated approval program, and is based on objective response rate and duration of response results from two multicenter, single-arm, open-label clinical trials, Study 10 and ARIEL2 Parts 1 and 2. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The ARIEL3 maintenance confirmatory study has completed enrollment and the ARIEL4 treatment confirmatory study is open for enrollment.
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 who have high-grade serous ovarian cancer and have had at least two prior lines of platinum-based chemotherapies are randomized to receive either placebo or rucaparib and the primary endpoint of the study is progression free survival, or PFS.
The primary efficacy analysis will evaluate, in a step-down process, 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 identify the size of the population with meaningful disease still present after a partial response to second-line platinum therapy.
Target enrollment in ARIEL3 was completed during the second quarter of 2016. Data from ARIEL3 are expected mid-2017. Clovis has not yet been notified by the independent statistician that the required 70 percent of events in the mutant BRCA population has been reached, which will trigger the final analysis of the data. Pending positive data from ARIEL3, Clovis intends to follow up with a supplemental NDA for second-line maintenance therapy in women with ovarian cancer who have responded to platinum-based therapy.
The ARIEL4 confirmatory study, which is open for enrollment, 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.
Also during the quarter, the Company submitted an MAA for rucaparib to the European Medicines Agency for the same ovarian cancer treatment indication that was submitted to the U.S. FDA. Clovis anticipates an opinion from the Committee for Medicinal Products for Human Use (CHMP) in late 2017, and, pending a favorable opinion from CHMP, an approval would follow shortly thereafter.
In October, in support of the anticipated U.S. commercial launch of rucaparib, Clovis entered into a long-term manufacturing and supply agreement with Lonza, the manufacturer of the active pharmaceutical ingredient (API) for rucaparib. This new agreement for a dedicated manufacturing line is expected to provide security of supply and reduce cost of goods over time.
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.
Rucaparib Clinical Development
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. Several 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.
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.
The cooperative group-sponsored MITO-25 study evaluating rucaparib and bevacizumab in combination as a first-line maintenance therapy for advanced ovarian cancer; and
The investigator-initiated RUBY study in women with breast cancer whose tumors have a somatic BRCA mutation or homologous recombination deficient (HRD) signature other than a known germline BRCA mutation; and
The investigator-initiated PLATFORM study in gastroesophageal cancer in the first-line maintenance setting and
The Phase 1b combination study of Genentech’s cancer immunotherapy Tecentriq (atezolizumab; anti-PDL1) and rucaparib for the treatment of gynecological cancers, with a focus on ovarian cancer.
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 FDA-approved companion diagnostic for Rubraca. The indication for Rubraca is approved under the FDA’s accelerated approval program based on objective response rate and duration of response, and is based on results from two multicenter, single-arm, open-label clinical trials. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Please visit rubraca.com for more information.
About Rucaparib
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 Europe for an ovarian cancer treatment indication was submitted and accepted during the fourth quarter of 2016. Additionally, rucaparib is being developed as maintenance therapy for ovarian cancer in the ARIEL3 trial for patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA, as well as biomarker negative patients. Data from ARIEL3 are expected in mid-2017, which, pending positive data, is expected to be followed by the submission of a sNDA for a second line or later maintenance indication. Rucaparib is also being developed in patients with mutant BRCA tumors and other DNA repair deficiencies beyond BRCA – commonly referred to as homologous recombination deficiencies, or HRD. Studies open for enrollment or under consideration include prostate, breast, pancreatic, gastroesophageal, bladder and lung cancers. Clovis holds worldwide rights for rucaparib.