Date: 2015-08-03
Type of information: Submission of a Market Application in the US
Product name: CO-1686
Compound: rociletinib
Therapeutic area: Cancer - Oncology
Action mechanism: kinase inhibitor/tyrosine kinase inhibitor. CO-1686 is an oral, targeted covalent inhibitor of mutant forms of the epidermal growth factor receptor (EGFR) for the treatment of non-small cell lung cancer in patients with initial activating EGFR mutations as well as the dominant resistance mutation T790M. Rociletinib was given Breakthrough Therapy designation by the FDA in May 2014.
Company: Clovis Oncology (USA - CO)
Disease: treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation
Latest news: * On April 12, 2016, Clovis Oncology announced that the FDA Oncologic Drugs Advisory Committee (ODAC) met to discuss approval of the New Drug Application (NDA) for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the T790M mutation. The Committee recommended that the FDA wait to see results from TIGER-3, Clovis’ ongoing Phase 3, randomized, controlled trial of rociletinib, before making a decision on approval of the treatment. Patient enrollment for the trial is expected to complete in late 2018. The FDA set a target action date of June 28, 2016 under the Prescription Drug User Fee Act (PDUFA). * On February 12, 2016, Clovis Oncology announced that the FDA has scheduled the New Drug Application (NDA) for rociletinib for discussion by the Oncologic Drugs Advisory Committee (ODAC) on April 12, 2016. * On December 15, 2015, Clovis Oncology announced that the FDA has extended the Prescription Drug User Fee Act (PDUFA) date for Clovis’ New Drug Application (NDA) for rociletinib by the standard extension period of three months with the new goal date of June 28, 2016. Clovis submitted a Major Amendment on November 16, 2015 in response to the FDA’s request for additional clinical data for both the 500mg and 625mg BID dose patient groups for rociletinib. As expected, the FDA extended the PDUFA goal date to allow additional time for review of the new information requested by the Agency. * On September 29, 2015, Clovis Oncology announced two major regulatory milestones for rociletinib, its investigational therapy for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation. The FDA has accepted Clovis’s New Drug Application (NDA) for rociletinib and has granted it priority review status with a Prescription Drug User Fee Act (PDUFA) action date of March 30, 2016. Additionally, the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for rociletinib. Europe’s Committee for Medicinal Products for Human Use (CHMP) granted Clovis an accelerated assessment for the drug, which reduces the time limit for CHMP to reach an opinion from 210 days to 150 days. Data from both the pivotal, single-arm TIGER-X and TIGER-2 clinical trials served as the basis for the U.S. and EU regulatory submissions for the treatment of advanced mutant EGFR T790M-positive lung cancer. * On August 3, 2015, Clovis Oncology announced that it has submitted its New Drug Application (NDA) regulatory filing to the FDA for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation as detected by an FDA approved test. In addition, Clovis has also submitted its Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) through the centralized procedure for rociletinib for the treatment of adult patients with mutant EGFR NSCLC who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation. Clovis Oncology is now preparing what could be its first U.S. commercial launch, and the company is also building a commercial organization in Europe. QIAGEN, Clovis’ companion diagnostic partner, intends to file a supplemental PMA application of its approved therascreen EGFR test with the FDA to allow for regulatory approval of the companion diagnostic concurrent with rociletinib approval. Analytical performance of the therascreen EGFR test has been established for 21 EGFR mutations, including the most prevalent resistance mutation, T790M. The test supports efficient laboratory workflow with real-time PCR technology on the FDA approved Rotor-Gene Q MDx, which is part of QIAGEN’s QIAsymphony family of laboratory solutions. * On July 1, 2015, Clovis Oncology announced that it has commenced the submission of a New Drug Application (NDA) regulatory filing to the FDA for rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGFR) non-small cell lung cancer (NSCLC) who have been previously treated with an EGFR-targeted therapy and have the EGFR T790M mutation as detected by an FDA approved test. Clovis agreed with FDA that the submission would be a rolling NDA and has filed the first component for potential accelerated approval of rociletinib in the U.S. The rolling NDA allows completed portions of an NDA to be submitted and reviewed by the FDA on an ongoing basis. The Company intends to complete the NDA submission by late July 2015. In addition, the Company intends to complete the Marketing Authorization Application (MAA) for rociletinib to the European Medicines Agency at the end of July. * On May 28, 2015, Clinigen Group announced the initiation of a global access program in Europe for rociletinib (CO-1686) which is being developed for the treatment of advanced non-small cell lung cancer. This program is intended to allow access to rociletinib for individual named patients with advanced or metastatic epidermal growth factor receptor (EGFR)-mutant T790M-positive NSCLC who have previously been treated with an EGFR-targeted therapy and for whom their physician determines that there is no satisfactory alternative therapy or rociletinib clinical trial available. Patients with an EGFR activating mutation often respond well to marketed EGFR inhibitor therapies, including Tarceva® (erlotinib), Iressa® (gefitinib) and Gilotrif® (afatinib). However, most will ultimately see their cancer progress, with approximately 60% developing acquired resistance from a second "gatekeeper" mutation, T790M. Currently, there are no therapies approved for the treatment of this mutation. Clinigen’s Managed Access Programs division will provide rociletinib to individual patients in selected countries in Europe initially, until the approval and launch of the drug. * On May 19, 2014, Clovis Oncology announced that the FDA has granted Breakthrough Therapy designation for the Company’s investigational agent CO-1686 as monotherapy for the treatment of second-line EGFR mutant NSCLC in patients with the T790M mutation. The Breakthrough Therapy designation was granted based on interim efficacy and safety results from an ongoing Phase 1/2 study of CO-1686. Interim results from an ongoing Phase 1/2 study of CO-1686 were presented at the 4th European Lung Cancer Conference (ELCC) in Geneva in late March. An objective response rate of 64 percent in 14 of 22 evaluable T790M positive patients was observed. CO-1686 is well-tolerated, with only one patient who discontinued treatment with CO-1686 due to adverse events. There was no evidence of systemic wild-type EGFR inhibition. The Company is currently enrolling two Phase 2 expansion cohorts of its Phase 1/2 study in EGFR mutant patients with the T790M mutation. Data from the expansion cohorts, combined with data from the TIGER2 study, in T790M positive patients directly after progression on their first and only TKI therapy, are expected to serve as the basis of an NDA submission for CO-1686 by mid-2015.
* On April 8, 2016, Clovis Oncology announced that the FDA posted briefing materials in advance of the Oncologic Drugs Advisory Committee (ODAC) meeting to discuss accelerated approval of the New Drug Application (NDA) for rociletinib. The FDA has set a target action date of June 28, 2016 for rociletinib under the Prescription Drug User Fee Act (PDUFA).
* On November 16, 2015, Clovis Oncology announced that during its regularly scheduled Mid-Cycle Communication Meeting held last week with the FDA, the agency requested additional clinical data for use in the efficacy analysis for both the 500mg and 625mg BID dose patient groups for rociletinib. In the Mid-Cycle Communication meeting, the FDA emphasized that its efficacy analysis would focus solely on confirmed responses. The New Drug Application (NDA) submitted by Clovis to the FDA contained immature data sets based on both unconfirmed response rates and confirmed response rates. These data sets were updated in the 90 day efficacy update the Company submitted at the end of October. As the rociletinib clinical trials were rapidly enrolling, Clovis presented interim data publicly and at medical meetings and these data therefore included a data set based primarily on unconfirmed responses. This was also true of the Company’s Breakthrough Therapy designation submission. In the Company’s NDA submission, both immature confirmed and unconfirmed response analyses were submitted. As the efficacy data have matured, the number of patients with an unconfirmed response who converted to a confirmed response was lower than expected. In the intent to treat analysis of the 79 patients in the 500mg dose group, the current confirmed response rate is 28 percent, and 34 percent in the 170 patients in the 625mg dose group, with an encouraging duration of response in both doses. The most frequent reasons that patients’ responses were not confirmed in a subsequent scan were due to progression, often due to brain metastasis, and due to subsequent scans not demonstrating tumor shrinkage greater than 30 percent. The Company anticipates that the review of this additional information will result in a delay of a potential approval. This additional review could lead to an extension of the Company’s March 30, 2016 Prescription Drug User Fee Act (PDUFA) date.
Patents:
Submission of marketing authorization application USA : 2015-08-03
Submission of marketing authorization application UE: 2015-08-03
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
