CENTER FOR DRUG EVALUATION AND
`RESEARCH
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`APPLICATION NUMBER:
`202107Orig1s000
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`APPROVAL LETTER
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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 202107
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`Food and Drug Administration
`Silver Spring MD 20993
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`NDA APPROVAL
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`Corcept Therapeutics
`Attention: Luana Staiger
`Regulatory Affairs
`149 Commonwealth Drive
`Menlo Park, CA 94025
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`Dear Ms. Staiger:
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`Please refer to your New Drug Application (NDA) dated April 15, 2011, received
`April 18, 2011, submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic
`Act (FDCA) for Korlym (mifepristone) tablets, 300 mg.
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`We acknowledge receipt of your amendments dated April 19, 22, and 25, June 9 and 30,
`July 11, 12, 13 (2), 20, and 27, August 4 (2) and 12, September 21 (2), October 4, 17, and 19,
`November 10, 18, and 21, and December 7 and 14, 2011, January 19 and 23, and February 6, 9,
`and 15, 2012. We also acknowledge receipt of your e-mails dated February 17, 2012, which
`includes the agreed-upon labeling.
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`This new drug application provides for the use of Korlym (mifepristone) for the control of
`hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's
`syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or
`are not candidates for surgery.
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`We have completed our review of this application, as amended. It is approved, effective on the
`date of this letter, for use as recommended in the enclosed agreed-upon labeling text.
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
`Guide).
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`Reference ID: 3089791
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`NDA 202107
`Page 2
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`Information on submitting SPL files using eLIST may be found in the guidance for industry
`titled “SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible via publicly available labeling repositories.
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`CONTAINER LABELS
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`We acknowledge your February 12, 2012, submission containing final printed container labels.
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`Submit final printed container labels that are identical to the enclosed container labels as soon as
`they are available, but no more than 30 days after they are printed. Please submit these labels
`electronically according to the guidance for industry titled “Providing Regulatory Submissions in
`Electronic Format – Human Pharmaceutical Product Applications and Related Submissions
`Using the eCTD Specifications (June 2008).” Alternatively, you may submit 12 paper copies,
`with 6 of the copies individually mounted on heavy-weight paper or similar material. For
`administrative purposes, designate this submission “Final Printed Carton and Container
`Labels for approved NDA 202107.” Approval of this submission by FDA is not required
`before the labeling is used.
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`Marketing the product with FPL that is not identical to the approved labeling text may render the
`product misbranded and an unapproved new drug.
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`POSTMARKETING REQUIREMENTS UNDER 505(o)
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`Section 505(o)(3) of the FDCA authorizes FDA to require holders of approved drug and
`biological product applications to conduct postmarketing studies and clinical trials for certain
`purposes, if FDA makes certain findings required by the statute.
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`We have determined that an analysis of spontaneous postmarketing adverse events reported
`under subsection 505(k)(1) of the FDCA will not be sufficient to assess a known serious risk of
`endometrial hyperplasia and retinopathy associated with long-term exposure to Korlym
`(mifepristone) therapy, and to assess a signal of a serious risk of major adverse cardiovascular
`events due to reductions in HDL-cholesterol associated with the use of Korlym (mifepristone).
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`Furthermore, the new pharmacovigilance system that FDA is required to establish under section
`505(k)(3) of the FDCA will not be sufficient to assess this serious risk.
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`Reference ID: 3089791
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`NDA 202107
`Page 3
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`Therefore, based on appropriate scientific data, FDA has determined that you are required to
`conduct the following:
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`1875-1 A drug utilization study to better characterize the reporting rates of adverse events
`associated with the long-term use of Korlym (mifepristone). These data will
`provide a denominator for the adverse events of special interest (endometrial
`hyperplasia and/or vaginal bleeding, retinopathy, and major adverse
`cardiovascular events) reported through enhanced pharmacovigilance and
`associated with long-term exposure to Korlym (mifepristone) therapy.
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`The timetable you submitted on February 12, 2012, states that you will conduct this study
`according to the following schedule:
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`Final Protocol Submission: 06/2012
`Interim Report Submissions: 08/2012
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`02/2013
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`02/2014
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`02/2015
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`02/2016
`Final Report Submission:
`02/2017
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`Finally, increased exposure to mifepristone is associated with serious risks for severe
`hypokalemia and adrenal insufficiency. Mifepristone is a CYP3A4 substrate and it is anticipated
`that co-administration with strong CYP3A4 inhibitors may be necessary. We have determined
`that only a clinical trial (rather than a nonclinical or observational study) will be sufficient to
`characterize the effect of co-administration of strong CYP3A4 inhibitors on increasing
`mifepristone drug levels and to assess the potential for the known serious risks of severe
`hypokalemia and adrenal insufficiency.
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`Therefore, based on appropriate scientific data, FDA has determined that you are required to
`conduct the following:
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`1875-2 A drug-drug interaction clinical trial to determine a quantitative estimate of the
`change in exposure of mifepristone following co-administration of ketoconazole
`(a strong CYP3A4 inhibitor).
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`The timetable you submitted on February 12, 2012, states that you will conduct this trial
`according to the following schedule:
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`Final Protocol Submission: 08/2012
`Trial Completion:
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`05/2013
`Final Report Submission:
`08/2013
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`Submit the protocols to your IND 076480, with a cross-reference letter to this NDA. Submit all
`final reports to your NDA.
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`Reference ID: 3089791
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`NDA 202107
`Page 4
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`Prominently identify the submission with the following wording in bold capital letters at the top
`of the first page of the submission, as appropriate: “Required Postmarketing Protocol Under
`505(o)”, “Required Postmarketing Final Report Under 505(o)”, “Required Postmarketing
`Correspondence Under 505(o)”.
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`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any
`study or clinical trial required under this section. This section also requires you to periodically
`report to FDA on the status of any study or clinical trial otherwise undertaken to investigate a
`safety issue. Section 506B of the FDCA, as well as 21 CFR 314.81(b)(2)(vii) requires you to
`report annually on the status of any postmarketing commitments or required studies or clinical
`trials.
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`FDA will consider the submission of your annual report under section 506B and 21
`CFR 314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section
`505(o)(3)(E)(ii) provided that you include the elements listed in 505(o) and 21 CFR
`314.81(b)(2)(vii). We remind you that to comply with 505(o), your annual report must also
`include a report on the status of any study or clinical trial otherwise undertaken to investigate a
`safety issue. Failure to submit an annual report for studies or clinical trials required under 505(o)
`on the date required will be considered a violation of FDCA section 505(o)(3)(E)(ii) and could
`result in enforcement action.
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`RISK EVALUATION AND MITIGATION STRATEGY REQUIREMENTS
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`We acknowledge receipt of your submission dated April 15, 2011, of a proposed risk evaluation
`and mitigation strategy (REMS). We have determined that, at this time, a REMS is not
`necessary for Korlym (mifepristone) to ensure that its benefits outweigh its risks. We will notify
`you if we become aware of new safety information and make a determination that a REMS is
`necessary.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert
`to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert, at the time of initial dissemination or publication, accompanied by a Form FDA
`2253. For instruction on completing the Form FDA 2253, see page 2 of the Form.
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`Reference ID: 3089791
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`NDA 202107
`Page 5
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`For more information about submission of promotional materials to the Office of Prescription
`Drug Promotion (OPDP), see
`http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`We request that for a period of 5 years, you submit reports of all cases of endometrial
`hyperplasia and/or vaginal bleeding, retinopathy, and major adverse cardiovascular events as 15-
`day alert reports, and that you provide analyses of clinical trial and post-marketing cases of these
`adverse events of special interest in your periodic safety update reports.
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`If you have any questions, please call Ms. Jena Weber, Regulatory Project Manager, at
`301-796-1306.
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`Sincerely,
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`{See appended electronic signature page}
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`Mary H. Parks, M.D.
`Director
`Division of Metabolism and Endocrinology Products
`Office of Drug Evaluation II
`Center for Drug Evaluation and Research
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`ENCLOSURES:
`Content of Labeling (package insert and Medication Guide)
`Container Labels
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`Reference ID: 3089791
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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
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`MARY H PARKS
`02/17/2012
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`Reference ID: 3089791
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