On February 21, 2018 Clovis Oncology, Inc. (NASDAQ: CLVS) reported an update to the ongoing regulatory review for the Marketing Authorization Application (MAA) for rucaparib tablets as monotherapy for the treatment of a limited population of advanced ovarian cancer patients with deleterious BRCA mutation (germline and/or somatic) (Press release, Clovis Oncology, FEB 21, 2018, View Source;p=RssLanding&cat=news&id=2333860 [SID1234524094]). The indication under consideration by the Committee for Medicinal Products for Human Use (CHMP) focuses on a subset of platinum-sensitive disease where there is particular unmet medical need.
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Following a Scientific Advisory Group (SAG) – Oncology last week and an oral explanation this week, the European Union’s (EU) European Medicines Agency (EMA) CHMP has communicated a positive trend vote for the rucaparib MAA and their intention to hold a final vote on the treatment indication at their March meeting (March 19-22, 2018).
"We are pleased with this positive trend vote and the potential for a formal positive vote on the later-line treatment indication next month, especially for a patient population with a significant unmet clinical need," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "This potential approval also paves the way to a rapid review and potential CHMP vote for the maintenance indication by year-end in an earlier-line and all-comers population for women with advanced ovarian cancer."
The CHMP application for the treatment indication currently under review was submitted during the fourth quarter of 2016 and was based on objective response rate and duration of response results from two multicenter, single-arm, open-label clinical trials, Study 10 and ARIEL2, in women with advanced BRCA-mutant ovarian cancer who had progressed after two or more prior chemotherapies. Patients received rucaparib orally 600 mg twice daily as monotherapy until disease progression or unacceptable toxicity. Objective response rate (ORR) and duration of response (DOR) were assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The most common Grade 3/4 adverse event was anemia.
Pending an approval for the treatment indication, Clovis plans to submit a variation to the MA based on data from the phase 3 ARIEL3 clinical trial, which found that rucaparib significantly improved progression-free survival in all ovarian cancer patient populations studied. ARIEL3 is a double-blind, placebo-controlled 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) BRCA-mutant (BRCAmut+); 2) HRD-positive (HRD+) inclusive of BRCA-mutant; and finally, 3) the intent-to-treat population, or all patients treated in ARIEL3. The variation to the MA will be directed at the broader intent-to-treat or "all comers" population.
Clovis announced positive topline results from the ARIEL3 clinical trial in June 2017. The comprehensive dataset from the trial was presented at the 2017 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Conference in Madrid, Spain,i and subsequently published in The Lancet.ii
In the event of a negative vote next month by the CHMP, Clovis is prepared to submit a new MAA for the maintenance indication.
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. In December 2017, the U.S. Food and Drug Administration (FDA) accepted the company’s supplemental New Drug Application (sNDA) for rucaparib for a second line or later maintenance treatment indication in ovarian cancer based on the ARIEL3 data. The FDA granted priority review status to the application with a Prescription Drug User Fee Act (PDUFA) date of April 6, 2018. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung and bladder cancers. Clovis holds worldwide rights for rucaparib. Rucaparib is an unlicensed medical product in the EU.