BOULDER, Colo.--Clovis Oncology, Inc. (NASDAQ: CLVS) announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the Company's investigational agent rucaparib as monotherapy treatment of advanced ovarian cancer in patients who have received at least two lines of prior platinum-containing therapy, with BRCA-mutated tumors, inclusive of both germline BRCA (gBRCA) and somatic BRCA (sBRCA) mutations.
Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 being developed for the treatment of platinum-sensitive ovarian cancer, specifically in patients with tumors with BRCA mutations and other DNA repair deficiencies beyond BRCA, commonly referred to as "BRCA-like" or "BRCAness." The Breakthrough Therapy designation was granted based on interim efficacy and safety results from two ongoing Phase 2 studies of rucaparib in ovarian cancer, including a Phase 2 study in women with gBRCA mutations, and the ARIEL2 treatment study.
A clinical data update from the ARIEL2 study presented last week at the 2015 Annual Meeting on Women's Cancer® demonstrated that seventy percent (16/23) of evaluable BRCA-mutant patients achieved a RECIST and/or CA-125 response, and 65% (15/23) achieved a RECIST response. Responses were observed in both germline and somatic BRCA-mutant tumors.
"It is a distinct achievement for a company our size to have been granted Breakthrough Therapy designation for two separate products under development, and especially in less than one year," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "In the case of rucaparib, we believe it is in recognition of the encouraging response rate observed in women with BRCA-mutated advanced ovarian cancer treated with rucaparib, and this designation reinforces the unique profile of rucaparib among PARP inhibitors, as well as our leadership in the differentiated clinical development of a PARP inhibitor. This includes prospectively demonstrating meaningful activity in an additional group of advanced ovarian cancer patients whose tumors are not mutant BRCA, but whose tumors possess similar DNA repair deficiencies that behave like BRCA mutations. Rucaparib is the only PARP inhibitor to have shown activity in this broader, but still selected, patient population."
"Women with ovarian cancer are in need of better therapeutic options, and there is great focus on the potential of PARP inhibitors; data presented to date in mutant BRCA patients treated with rucaparib are very encouraging, as is the Breakthrough Therapy designation conferred by the FDA," 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 two principal investigators of the ARIEL3 study. "I am very enthusiastic about the substantive progress made by Clovis with both rucaparib and its patient selection tool that appears to be moving beyond BRCA to efficiently identify responder versus non-responder populations. Continuing successful development of this drug and its companion diagnostic will be a huge advance for women with this disease. Importantly, these data suggest that the majority of women tested might benefit from rucaparib treatment. We hope that the ARIEL2 extension study in around 300 women, and the randomized ARIEL3 trial in 540 women, will offer definitive support both for rucaparib and the companion diagnostic."
A clinical data update from the ARIEL2 study presented last week at the 2015 Annual Meeting on Women's Cancer®demonstrates encouraging activity and safety in women with advanced, platinum-sensitive ovarian cancer with gBRCA and sBRCA mutations. Seventy percent (16/23) of evaluable BRCA-mutant patients achieved a RECIST and/or CA-125 response, and 65% (15/23) achieved a RECIST response. Responses were observed in both germline and somatic BRCA-mutant tumors. In addition, data presented last week further demonstrate that Clovis' proprietary BRCA-like DNA signature, run by its partner Foundation Medicine, successfully predicts which ovarian cancer patients respond to rucaparib therapy. In patients with normal BRCA genes, rucaparib activity was substantially higher for those with the prospectively-defined BRCA-like HRD signature versus biomarker negative patients. Forty-eight percent (12/25) of patients with the BRCA-like signature achieved a RECIST and/or CA-125 response, and 40% (10/25) achieved a RECIST response. In biomarker negative patients, few responses were observed: eight percent (1/13) of patients achieved a RECIST and/or CA-125 response.
These data also demonstrate that rucaparib is well-tolerated. At the recommended Phase Two dose of 600mg BID, the most common treatment-related adverse events (AEs) reported in ≥15 percent of all patients (n=121) included nausea, fatigue, transient ALT/AST elevations, dysgeusia, constipation, anemia/low hemoglobin, decreased appetite, vomiting and diarrhea. These events were mostly Grade 1/2; the only common grade 3/4 toxicity was anemia/low hemoglobin.
The next update of rucaparib clinical data, including outcomes data on the complete Part One ARIEL2 patient population, will be presented in an oral presentation at the 2015 American Society of Clinical Oncology Annual Meeting in late May/early June.
ARIEL Pivotal Study Program
The ARIEL (Assessment of Rucaparib in Ovarian Cancer Trial) program is a novel, integrated translational-clinical program designed to accurately and prospectively identify patients with tumor genomics associated with benefit from rucaparib therapy.
The global ARIEL2 study, initiated in Q4 2013, has completed enrollment of 206 ovarian cancer patients with relapsed, platinum-sensitive disease. The single-arm, open-label Phase 2 study is designed to prospectively test molecular features that predict sensitivity to rucaparib using DNA sequencing to evaluate each patient's tumor. ARIEL2 was recently expanded into a registration study (the ARIEL2 extension), which will include an additional approximately 300 women with recurrent disease after at least three prior lines of chemotherapy, and data from this study are planned to serve as the basis of a New Drug Application (NDA) filing for the treatment of ovarian cancer in 2016.
The global ARIEL3 pivotal study is currently enrolling a total of 540 patients, in a randomized, double-blind Phase 3 study that compares the effects of rucaparib versus placebo. The study will evaluate whether maintenance rucaparib treatment in platinum-sensitive, high-grade ovarian cancer patients can extend the period of time for which a response to a prior chemotherapy is maintained. Efficacy is assessed in a pre-specified step-down manner, first in tumor BRCA-mutant patients, then in a larger group of patients with the BRCA-like signature, and finally in all randomized patients. The Company anticipates completing enrollment in the study within the next year.
In addition to the ARIEL program in ovarian cancer, the Company is exploring rucaparib in other solid tumor types with significant BRCA and BRCA-like populations including breast, gastroesophageal and pancreatic.
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 to treat serious or life-threatening medical conditions when preliminary clinical evidence demonstrates that the drug may have substantial improvement on at least one clinically significant endpoint over available therapies. 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.
Rucaparib is an oral, potent inhibitor of PARP1 and PARP2 being developed for the treatment of platinum-sensitive ovarian cancer in patients with BRCA mutations (genes that are linked to breast and ovarian cancers) and other DNA repair deficiencies. For information about rucaparib studies in ovarian cancer, please visit www.arielstudy.com.
About Ovarian Cancer
Over 90% of ovarian cancer arises from the uncontrolled growth and replication of epithelial cells which form the surface of the ovary. Cancer involving this type of cell is known as epithelial ovarian cancer. High grade serous carcinoma is a subtype of epithelial ovarian cancer accounting for approximately 70 percent of cases. If detected at a very early stage, ovarian cancers can usually be removed surgically and this can be potentially curative. However, there are often no clearly identifiable initial symptoms and in approximately 90 percent of high grade serous ovarian cancer cases, the cancer has spread to other parts of the body before a person is diagnosed.
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 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.