throbber
CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`
`
`
`APPLICATION NUMBER:
`202107Orig1s000
`
`
`OTHER REVIEW(S)
`
`
`
`
`
`

`

`RPM FILING REVIEW
`
`(Including Memo of Filing Meeting)
`To be completed for all new NDAs, BLAs, and Efficacy Supplements [except SE8 (labeling
`change with clinical data) and SE9 (manufacturing change with clinical data]
`
`A lication Information
`
`Proprietary Name: Korlym
`Established/Proper Name: mifepristone
`Dosage Form: Tablets
`Stren ths: 300 my
`
`Applicant: CORCEPT Therapeutics
`A ~ cut for A licant: N/A
`
`Date of Application: 4/15/1 1
`Date of Receipt: 4/ 18/1 1
`Date clock started after UN: N/A
`
`PDUFA Goal Date: 2/18/12
`
`Action Goal Date (if different):
`2/17/12
`
`
`
`Date of Filin { Meetin 7: 6/14/11
`Filin { Date: 6/17/11
`Chemical Classification: 123 etc. ori ' Ial NDAs on]
`5
`
`Proposed indication: 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
`diabetes mellitus type 2 or glucose intolerance and have failed surgery or are not candidates for surgery.
`
`Type of Original NDA:
`AND (if applicable)
`Type of NDA Supplement:
`
`505(b)(2)
`
`If505(b)(2).° Draft the “505(b)(2) Assessment”form found at:
`h
`://inside. do. ov:9003/CDER/0 ceo 'ewDru s/InlmediateO ce/UCM027499
`and re er to -
`I endixA or urther in ormation.
`
`Review Classification:
`
`Standard
`
`Ifthe application includes a complete response to pediatric W71, review
`classification is Priority.
`
`Ifa tropical diseasepriority review voucher was submitted, review
`classification is Priority.
`
`Resubmission after withdrawal? No
`
`Resubmission after refuse to file? No
`
`Part 3 Combination Product? No
`
`[:1 Convenience kit/Co—package
`E] Pie-filled drug delivery device/system
`D Pre-filled biologic delivery device/system
`lfyes, can!!!“ the Office 01'Combination
`Products (OCP) and copy them on all Inter— [:1 Device coated/impregnated/combined with drug
`cam" ”WWI“
`El Device coated/impregnated/combined with biologic
`E] Drug/Biologic
`E] Separate products requiring cross-labeling
`E] Possible combination based on cross-labeling of separate
`roducts
`
`Other (drug/device/biological product)
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`1
`
`

`

`
`
`El Fast Track
`E] Rolling Review
`X Orphan Designation
`
`E] Rx-to-OTC switch, Full
`I: Rx—to-OTC switch, Partial
`E] Direct-to—OTC
`
`Other:
`
`El PMC response
`[I PMR response:
`El FDAAA [505(0)]
`El PREA deferred pediatric studies [21 CFR
`314.55(b)/21 CFR 601.27(b)]
`El Accelerated approval confirmatory studies (21 CFR
`314.510/21 CFR 601.41)
`I] Animal rule postrnarketing studies to verify clinical
`benefit and safe
`21 CFR 314.610/21 CFR 601.42
`
`Collaborative Review Division (if OTC product): N/A
`
`List referenced IND Numbers:
`
`"N" and 076480
`
`Goal Dates/Product Names/Classification Pro - rties
`
`PDUFA and Action Goal dates correct in tracking system?
`
`Ifno, ask the document room std/fto correct them immediately.
`These are the dates used or calculating ins
`
`Are the proprietary. established/proper. and applicant names
`correct in tracking system?
`
`Ifno, ask the document room stafl'to make the corrections. Also,
`ask the document room staffto add the established/proper name
`to the supporting IND(s) ifnot already entered into tracking
`5 stem.
`
`Is the review priority (S or P) and all appropriate
`classifications/properties entered into tracking system (e. g.,
`chemical classification. combination product classification,
`505(b)(2). orphan drug)? For MAWDA supplements, check
`the Application and Supplement Notification Checklistsfor a list
`ofall classifications/properties at:
`h
`://inside. da. ov:9003/CDER/0 ceo usinessProcessSu ort/ucm163970Jlt
`E
`
`Ifno, ask the document room stafl'to make the appropriate
`entries.
`
`A lication Inte_ri Polic
`
`Is the application afi‘ected by the Application Integrity Policy
`(AIP)? Check theAIP list at:
`h min/Anvil do. ov/ICECI/En orcemenMcrions/A Iicalionlme
`i‘“""‘"a‘“'“°“‘me“‘°°“““"
`
`'
`
`'PoIi
`
`
`
`/lle ault
`
`II.—
`
`If affected by AIP. has OC/DMPQ been notified of the
`submission? If yes, date notified:
`—EE-—IIE]
`Is Form 3397 (User Fee Cover Sheet) included with
`‘/
`authorized signature?
`
`Version: l/24/12
`
`Reference ID: 3090221
`
`2
`
`

`

`
`
`User Fee Status
`
`Ifa userfee is required and it has not been paid (and it
`is not exempted or waived), the application is
`unacceptableforfilingfollowing a 5-day graceperiod.
`Review stops. Send Unacceptablefor Filing (07V) letter
`and contact userfee stafl.‘
`
`Exempt (orphan)
`
`Ifthefirm is in arrearsfor otherfees (regardless of
`whether a userfee has been paidfor this application),
`the application is unacceptableforfiling (5-day grace
`period does not apply). Review stops. Send UN letter
`and contact the userfee stafl.‘
`
`Not in arrears
`
`505(b)(2)
`(NDAs/NDA Effica Sn lements o
`
`difi‘erence is that the extent to which the active ingredient(s)
`is absorbed or otherwise made available to the site of action
`
`is less than that of the reference listed drug (RLD)? [see 21
`CFR 314.54(b)(1)].
`Is the application for a duplicate of a listed drug whose only
`difference is that the rate at which the proposed product’s
`active ingredient(s) is absorbed or made available to the site
`of action is unintentionally less than that of the listed drug
`[see 21 CFR 314.54(b)(2)]?
`
`Ifyou answered yes to any ofthe above questions, the application
`may be refusedforfiling under 21 CFR 314.101(d)(9). Contact
`the (b 2 review staj in the Immediate 0] ice 0 New
`_'
`
`Is there unexpired exclusivity on the active moiety (e.g.. 5-
`year. 3-year. orphan or pediatric exclusivity)?
`Check the Electronic Orange Book at:
`hwy/uwmaccessdata.(do.gov/scrigts/cder/ob/detault.cg
`
`If es. lease list below:
`
`
`
`Ifthere is unexpired, 5—year exclusivitv remaining on the active moietyfor the proposed drugproduct, a 505(b)(2)
`application cannot be submitted until the period ofexclusivity expires (unless the applicantprovides paragraph IV
`patent certification; then an application can be submittedfour years after the date ofapproval.) Pediatric
`exclusivitv will extend both ofthe timefi‘ames in this provision by 6 months. 21 CFR 108(b)(2). Unetpired, 3-_vear
`
`Does another product (same active moiety) have orphan
`exclusivity for the same indication? Check the Orphan Drug
`Designations and Approvals list at:
`
`Version: 1/2411 2
`
`Reference ID: 3090221
`
`3
`
`

`

`
`
`If another product has orphan exclusivity, is the product
`considered to be the same product according to the orphan
`drug definition of sameness [see 21 CFR 316.3(b)(13)]?
`
`I
`
`Ifyes, consult the Director, Division ofRegulatory Policy II,
`0] Ice 0 Re nlato Poli
`v
`Has the applicant requested 5-year or 3-year Waxman-Hatch
`exclusivity? (NDAsAVDA eflicaqi supplements only)
`
`\/
`
`7 years requested exclusivity
`
`Note: An applicant can receive exclasivitv without requesting it;
`there are, re nestin exclusivitv is not re aired.
`
`Is the proposed product a single enantiomer of a racemic drug
`previously approved for a different therapeutic use (NDAs
`onl )?
`If yes, did the applicant: (a) elect to have the single
`enantiomer (contained as an active ingredient) not be
`considered the same active ingredient as that contained in an
`already approved racemic drug, and/or (b): request
`exclusivity pursuant to section 505(u) of the Act (per
`FDAAA Section 1 1 13)?
`
`Ifyes, contact Mary Ann Holovac, Director ofDrug Information,
`OGD/DLPS/LRB.
`
`‘/
`
`'/
`
`Format and Content
`
`All paper (except for COL) Do not check mixed submission ifthe only electronic component
`
`is the content 0 labelin COL).
`
`If mixed (paper/electronic) submission, which parts of the
`a lication are submitted in electronic format?
`
`Overall Format/Content
`
`If electronic submission, does it follow the eCTD
`-
`'dance?1
`Index: Does the submission contain an accurate
`com DIChCDSiVC index?
`
`Is the submission complete as required under 21 CFR 314.50
`(NDAs/NDA eflicacy supplements) or under 21 CFR 601.2
`(BLAs/BLA eflicaqv supplements) including:
`
`E] legible
`E] English (or translated into English)
`C] pagination
`E] navi able h perlinks (electronic submissions onl )
`
`
`
`://www fda. ov/downloads/Dru s/GuidanceCon lianceReh lato Information/Guidances/ucn1072349.
`
`
`
`Version: l/24/12
`
`Reference ID: 3090221
`
`4
`
`

`

`
`
`If no, exlain.
`
`divided manufacturing arrangement?
`
`BLAsonly:Companionapplicationreceivedifasharedor
`
`If es. BLA #
`Forms and Certifications
`
`I
`
`Electronicforms and certifications with electronic signatures (scanned, digital, or electronic — similar to DARRTS,
`e.g., /s/) are acceptable. 0tl1envise,_paperfonns and certifications with hand—written signatures must be included.
`Forms include: userfee cover sheet (3397), application form (356h), patent information (3542a), financial
`disclosure (3454/3455), and clinical trials (3674); Certifications include: debarment certification, patent
`certi cation(s), eld co icerti cation, and ediatric cer ‘ cation.
`A lication Form
`
`\E
`
`
`22-E-!_E-EI-E-fi-fi_fi-EI-I
`
`Is form FDA 356h included with authorized signature per 21
`CFR 314.50(a)?
`
`Ifforeign applicant, a (1.8. agent must sign theform [see 21 CFR
`314. 50(a (5 .
`
`on the form/attached to the form?
`
`Patent Information
`
`(NDAs/NDA effica
`
`su. lements on
`
`)
`
`Is patent information submitted on form FDA 3542a per 21
`CFR 314.53(c)?
`
`Financial Disclosure
`Are financial disclosure forms FDA 3454 and/or 3455
`
`included with authorized signature per 21 CFR 54.4(a)(1) and
`(3)?
`
`Forms must be signed by the APPLICANT, not an Agent [see 21
`CFR 54.2(g)].
`
`*
`
`I
`
`Note: Financial disclosure is requiredfor bioequivalence studies
`that are the basis or a I roral.
`
`Clinical Trials Database
`
`Is form FDA 3674 included with authorized signature?
`
`Ifyes, ensure that the application is also coded with the
`supporting document category, “Form 36 74. ”
`
`Ifno, ensure that language requesting submission oftheform is
`included in the acknowled ement letter sent to the a licant
`Debarment Certification
`
`Is a correctly worded Debarment Certification included with
`authorized signature?
`
`Certification is not requiredfor supplements ifsubmitted in the
`original application; Ifforeign applicant, bo_th the applicant and
`the US. Agent must sign the certification filer Guidancefor
`Industry: Submitting Debarment Certifications].
`
`\E
`
`\E
`
`oE8H
`
`OOEEEaaa
`
`9
`
`Version: l/24/12
`
`Reference ID: 3090221
`
`5
`
`

`

`
`
`Note: Debannent Certification should use wording in FDCA
`Section 306(k)(1) i.e., "[Name ofapplicant] hereby certifies that it
`did not and will not use in any capacity the services ofany person
`debarred under section 306 ofthe Federal Food, Drug, and
`Cosmetic Act in connection with this application. " Applicant may
`not use wordin « such as, “To the best 0 mv knowled e_,_ "
`
`Field Copy Certification
`DAs/NDA effica
`sn. lements on]
`
`NA Comment
`
`For paper submissions only: Is a Field Copy Certification
`(that it is a true copy of the CMC technical section) included?
`
`Field Copy Certification is not needed ifthere is no CMC
`technical section or ifthis is an electronic submission (the Field
`Oflice has access to the EDR)
`
`Ifmaroon field copyjacketsfrom foreign applicants are received,
`to the a ro riate teld 0] ice.
`
`Controlled Substance/Product with Abuse Potential mm-—
`I
`
`Is an Abuse Liability Assessment. including a proposal for
`scheduling. submitted per 21 CFR 314.50(d)(5)(vii)?
`
`Ifyes, date consult sent to the Controlled Substance Stafi’:
`
`For non—NMEs:
`
`Date ofconsult sent to Controlled Substance Stafl :
`
`
`
`—E_IIE]
`PREA
`/
`
`Does the application trigger PREA?
`
`Ifyes, notify PeRC RPM (PeRC meeting is requiredf
`
`Note: NDAs/BLAs/eflicacv supplementsfor new active ingredients,
`new indications, new dosageforms, new dosing regimens, or new
`routes ofadministration trigger PREL All waiver & deferral
`requests, pediatric plans, andpediatric assessment studies nmst be
`reviewed bv PeRC rior to a; moral o the a Ilication/su I lement.
`
`If the application triggers PREA. are the required pediatric
`assessment studies or a full waiver of pediatric studies
`included?
`
`If studies or full waiver not included, is a request for full
`waiver of pediatric studies OR a request for partial waiver
`and/or deferral with a pediatric plan included?
`
`If a request for full waiver/partial waiver/deferral is
`included, does the a lication contain the certification(s)
`
`://inside fda. ovz9003/CDER/OfficeofNeme s/PediatricandMatemalHealthStaff/ucmOZ7829.htm
`2h
`
`
`Version: 1/2411 2
`
`Reference ID: 3090221
`
`6
`
`

`

`
`
`required by FDCA Section SOSB(a)(3) and (4)?
`
`I no, reuest in 74-d¢ * letter
`
`BPCA (NDAs/NDA efficacy supplements only):
`
`Is this submission a complete response to a pediatric Written
`Request?
`
`Ifyes, notifly Pediatric Exclusivity Board RPM (pediatric
`exclusivi determination is re uired)’
`mm
`Is a proposed proprietary name submitted?
`/
`
`Ifyes, ensure that the application is also coded with the
`supporting document category, “Proprietary Name/Requestfor
`Review. ”
`
`_mmfl-—
`Is a REMS submitted?
`/
`REMS plan
`submitted
`
`Ifyes, send consult to OSE/DRISK and noti/jr 0C/
`OSI/DSC/PMSB via the DCRMSRMP mailbox
`
`_rescri.tion Labelin;_I Not applicable
`
`Check all types of labeling submitted.
`Package Insert (PI) Medication Guide
`Container Labels.
`
`—EEIII§l-—
`
`IsElectronicContentofLabeling(COL)submittedinSPL III-
`
`M III—
`
`If PI not submitted'in PLR format. was a waiver or
`
`deferral requested before the application was received or in
`the submission? If requested before application was
`submitted, what is the status of the request?
`
`Ifno waiver or deferral, request applicant to submit labeling in
`PLR ormat be are the (lin date.
`
`4 h
`
`_Ill—container labels consulted to OPDP?
`
`MedGuide, PPI. IFU (plus PI) consulted to OSE/DRISK?
`(send WORD version Ifavailable)
`
`Container labels. PI. PPI sent to OSE/DMEPA and
`
`appropriate CMC review office (OBP or ONDQA)?
`
`/
`
`J
`
`3h
`
`://inside fda. ov:9003/CDER/OfficeofNeme s/PediatiicandMatemalHealthStaff/ucmOZ7837.htm
`
`://inside fda. ovz9003/CDER/OfficeofNeme s/Stud End
`25576.htm
`
`intsandLabelin
`
`evelo mentTeam/ucmO
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`7
`
`

`

`OTC Labelin_
`Check all types of labeling submitted.
`
`Not Applicable
`I Outer carton label
`D Immediate container label
`D Blister card
`I] Blister backing label
`E] Consumer Information Leaflet (CIL)
`E] Physician sample
`
`Is electronic content of labeling (COL) submitted?
`
`I no, reIuest in 74-(1 I
`
`I letter.
`
`Are annotated specifications submitted for all stock keeping
`units (SKUs)?
`
`I no, reIuest in 74-4 I
`
`I letter.
`
`If representative labeling is submitted, are all represented
`SKUs defined?
`
`I no mates! in 74-41:
`
`letter.
`
`All labeling/packaging. and current approved Rx PI (if ---—
`switch sent to OSE/DMEPA?
`Other Consults
`m Comm
`Are additional consults needed?
`\/
`T Team. Maternal
`
`
`
`I es, s I eei; consult(s) and date(s) sent:
`Meetin MlllllteS/SPAS
`
`Date-(S).
`
`Date: 9/14/10
`
`Date(s):
`
`Version: 1/2411 2
`
`Reference ID: 3090221
`
`8
`
`

`

`
`
`
`
`NDA 202107 for mifepristone
`Filing Meeting – Tuesday June 14, 2011
`
`
`
`
`
`
`
`
`Sponsor: CORCEPT
`Drug: mifepristone 300mg Tablets
`
`
`
`Indication: For the treatment of hypercortisolism associated with Cushing’s Syndrome
`505(b)(2)
`
`
`
`
`
`Orphan Drug designation
`Paper submission
`
`Review Team:
`
`Division Director: Mary Parks, M.D.
`OND DMEP PM: Jena Weber, BS/Julie Marchick, MS
`CDTL: Dragos Roman, M.D.
`Clinical: Marina Zemskova, M.D.
`Chemistry: Xavier Ysern, Ph.D. (Su Tran, Ph.D., Ali Al-Hakim, Ph.D.)
`ONDQA PM: Kushboo Sharma
`Biopharm: Minerva Hughes, Ph.D. (Angelica Dorantes, Ph.D.)
`Pharm/Tox: Pat Brundage, Ph.D. (Todd Bourcier, Ph.D.)
`Pharm/Tox/Stats: Steve Thomson, Ph.D. (Karl Lin, Ph.D.)
`Clin Pharm Jee Eun Lee, Ph.D (Jaya Vaidyanathan, Ph.D.)
`Biometrics: Japo Choudhury, Ph.D. (Todd Sahlroot, Ph.D.)
`DMEP Safety: Amy Egan, M.D., John Bishai, Ph.D.
`DSI: Susan Leibenhaut, M.D. (Tejashri Purohit-Sheth, M.D.)
`DRISK: Suzanne Robottom, PharmD
`DDMAC: Sam Skariah, PharmD., Olga Salis, PharmD.
`DMEPA: Lena Maslov, PharmD., Zach Oleszczuk
`OSE: Rita Tossa, Claudia Karwoski, (Gerald Dal Pan, M.D.)
`OCC: Carla Cartwright, JD
`OC: Suzanne Barone
`ORP: Kristen Miller, Kristen Everett, Liz Dickinson, JD
`DCRP/QT: Devi Kozeli, RAC
`
`Receipt Date: April 18, 2011
`60-day Filing Date: June 17, 2011
`74-day letter: July 1, 2011
`Standard Review – 10 month Goal Date: February 17, 2012 (the 18th is a Sat).
`
`Filing Meeting: June 14, 2011
`Team Meeting#1: ~ August 2011
`Team Meeting #2: ~ November 2011
`Mid-Cycle Meeting: September 12, 2011
`AC Meeting: NN
`PeRC Meeting: N/A
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`9
`
`

`

`Primary Reviews completed: January 13, 2012
`Wrap-Up meeting: ~ January 13, 2012
`Secondary reviews completed: January 20, 2012
`D81 inspections complete: To be determined
`Send labeling and PMR/PMC to sponsor: ~ January 27, 2012
`CDTL review complete: January 27, 2012
`Action Package to Division Director: January 28, 2012
`Action letter sign-off: NLT February 17, 2012
`
`Consults requested or to be requested prn:
`
`DDMAC: labeling
`TQT team
`OSE: Trade Name
`
`DRISK: Labeling, Med Guide
`DSI: Clinical sites
`
`DRUP: Possibility of pregnancy in Cushing’s patients; what precautions or additional
`precautions should be taken?
`
`Discussion Points:
`
`Should an AC be scheduled? No.
`
`REMS — specific to indication under this NDA
`Inspections: DSI/clinical and CMC/EER
`Exempt from PREA (Orphan)
`
`Notes:
`
`Additional info requested for TQT team to review
`Review of PLR labeling underway
`Employee list not to be included in NDA AP
`
`REVIEW TEAM:
`
`Discipline/Organization
`
`Reviewer: MZemskova
`
`Regulatory Project Management
`
`JWeber
`
`Cross-Discipline Team Leader (CDTL) DRoman
`
`CPMS/TL:
`
`JMarchick
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`10
`
`

`

`
`
`
`
`Social Scientist Review (for OTC
`products)
`
`
`OTC Labeling Review (for OTC
`products)
`
`
`Clinical Microbiology (for antimicrobial
`products)
`
`
`Clinical Pharmacology
`
`
`Biostatistics
`
`
`Nonclinical
`(Pharmacology/Toxicology)
`
`Statistics (carcinogenicity)
`
`
`Immunogenicity (assay/assay
`validation) (for BLAs/BLA efficacy
`supplements)
`
`Product Quality (CMC)
`
`
`Quality Microbiology (for sterile
`products)
`
`CMC Labeling Review
`
`Facility Review/Inspection
`
`
`TL:
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`Reviewer:
`
`TL:
`
`
`DRoman
`NN
`
`
`
`NN
`
`
`
`NN
`
`
`
`JELee
`
`JVaidyanathan
`
`JChoudhury
`
`TSahlroot
`
`PBrundage
`
`TBourcier
`
`SThomson
`
`KLin
`
`NN
`
`NN
`
`XYsern
`
`STran
`
`NN
`
`
`
`XYsern
`
`STran
`
`SLeibenhaut
`
`TPurohit-Sheth
`
`Y
`NN
`
`
`
`NN
`
`
`
`NN
`
`
`
`Y
`
`Y
`
`Y
`
`Y
`
`Y
`
`Y
`
`N
`
`N
`
`
`
`
`
`Y
`
`Y
`
`
`
`
`
`Y
`
`Y
`
`Y
`
`Y
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`11
`
`

`

`
`
`OSE/DMEPA (proprietary name)
`
`“Ems“ ”M9
`
`--—
`mm“ (“M9 -—-
`-—-
`Bioresearch Monitoring (OSI) -—-
`-—-
`Controlled Substance Staff(CSS) -—-
`
`TL'
`
`NN
`
`Other reviewers
`
`DRUP TQT MHT
`
`——-
`
`
`
`
`FILING NIEETING DISCUSSION:
`
`GENERAL
`
`505(b)(2) filing issues?
`
`Per reviewers. are all parts in English or English
`translation?
`
`YES
`
`0
`
`0 0
`
`0 Electronic Submission comments
`
`Not Applicable
`
`CLINICAL
`
`FILE, review issues for 74-day letter
`
`Clinicalstudysite(s)inspections(s)needed? NOS—
`
`0 Advisory Committee Meeting needed?
`Ifno, for an originalM‘lE or BLA application, include the
`reason. For example:
`this drug/biologic is not the first in its class
`the ch'nical study design was acceptable
`the application did not raise significant satin?
`or etficacy issues
`the application did not raise significantpublic
`health questions on the role ofthe
`drug/biolog'c in the diagnosis, cure,
`miti ation treatment or ; revention ofa
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`12
`
`

`

`Not Applicable
`
`NO
`
`Not Applicable
`
`FILE, review issues for 74-day letter
`
`NO
`
`FILE, review issues for 74-day letter
`
`FILE, review issues for 74-day letter
`
`Not Applicable
`
`
`FILE, review issues for 74-day letter
`
`Not Applicable
`
`YES
`
`
` YES
` NO
`
`
`
` YES
` NO
`
`
` Not Applicable
`
`
`
`
`
`
` •
`
`
`•
`
`disease
`
` Abuse Liability/Potential
`
`If the application is affected by the AIP, has the
`division made a recommendation regarding whether
`or not an exception to the AIP should be granted to
`permit review based on medical necessity or public
`health significance?
`
`
`CLINICAL MICROBIOLOGY
`
`CLINICAL PHARMACOLOGY
`
`• Clinical pharmacology study site(s) inspections(s)
`needed?
`
`
`BIOSTATISTICS
`
`NONCLINICAL
`(PHARMACOLOGY/TOXICOLOGY)
`
`IMMUNOGENICITY (BLAs/BLA efficacy
`supplements only)
`
`PRODUCT QUALITY (CMC)
`
`Environmental Assessment
`
` •
`
`
`
` Categorical exclusion for environmental assessment
`(EA) requested?
`
`If no, was a complete EA submitted?
`
`
`If EA submitted, consulted to EA officer (OPS)?
`
`
`Quality Microbiology (for sterile products)
`
` •
`
` Was the Microbiology Team consulted for validation
`of sterilization? (NDAs/NDA supplements only)
`
`
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`13
`
`

`

`
`
`Facilig' Inspection
`
`0 Establishment(s) ready for inspection?
`
`.
`
`Establishment Evaluation Request (EER/TBP—EER)
`submitted to OMPQ?
`
`Facing/Microbiology Review (BLAs only)
`
`Not Applicable
`
`CMC Labefin Refiew
`
`REGULATORY PROJECT MANAGEMENT
`
`Signatory Authority: Mary Parks, M.D., Division Director
`
`REGULATORY CONCLUSIONS/DEFICIENCIES
`
`a The application is unsuitable for filing. Explain why:
`
`X
`
`The application. on its face. appears to be suitable for filing.
`
`Review Issues: review issues have been identified for the 74-day letter.
`
`
`
`R—eviewClassification. Standard Review
`
`ACTIONS ITEMS
`
`a BLA/BLA supplements. Iffiled send 60-day filing letter If priority review:
`
`Ensure that any updates to the review priority (S or P) and classifications/properties are
`entered into tracking system (e.g. chemical classification combination product
`classification, 505(b)(2)_ o han dru-V).
`If RTF. notify everybody who already received a consult request. OSE PM. and Product
`Quali PM (to cancel EER/TBP-EER).
`If filed. and the application is under AIP. prepare a letter either granting (for signature by
`Center Director) or denying (for signature by ODE Director) an exception for review.
`
`I
`
`I
`
`0
`
`notify sponsor in writing by day 60 (For BLAs/BLA supplements: include1n 60-day
`filin letter: For NDAs/NDA sun lements: see CST for choices)
`
`Version: l/24/12
`
`Reference ID: 3090221
`
`14
`
`

`

`
`
`X
`
`
`
`
`
`
`
`
`
`
`
`
`
`Jena M. Weber
`Regulatory Project Manager
`
`
`
`Julie Marchick
`Chief, Project Management Staff
`
`• notify OMPQ (so facility inspections can be scheduled earlier)
` Send review issues/no review issues by day 74
`
`Conduct a PLR format labeling review and include labeling issues in the 74-day letter
`
`BLA/BLA supplements: Send the Product Information Sheet to the product reviewer and
`the Facility Information Sheet to the facility reviewer for completion. Ensure that the
`completed forms are forwarded to the CDER RMS-BLA Superuser for data entry into
`RMS-BLA one month prior to taking an action [These sheets may be found at:
`http://inside.fda.gov:9003/CDER/OfficeofNewDrugs/ImmediateOffice/UCM027822]
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`February 16, 2012
`Date
`
`February 21, 2012
`Date
`
`Version: 1/24/12
`
`Reference ID: 3090221
`
`15
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`JENA M WEBER
`02/21/2012
`
`JULIE C MARCHICK
`02/21/2012
`
`Reference ID: 3090221
`
`

`

`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA #/Product Name:
`
`PMR/PMC Description:
`
`NDA 202107/Korlym (mifepristone)
`To obtain drug use data to better characterize the reporting rates of adverse
`events associated with the long-term use of Korlym (mifepristone).
`
`
` 06/17/2012
` 08/17/2012
` 02/17/2013
` 02/17/2014
` 02/17/2015
` 02/17/2016
` 02/17/2017
`
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`
`Interim report submissions:
`
`
`
`
`
`
`
`
`
`Final Report Submission:
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a
`pre-approval requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
` Other
`
`
`
`Endogenous Cushing’s syndrome is a rare disorder (~20,000 patients with Cushing’s syndrome in
`the U.S.). The indication for Korlym (mifepristone) is for the control of hyperglycemia due to
`hypercortisolism in adult patients with endogenous Cushing’s syndrome who have type 2 diabetes
`or glucose intolerance who have failed surgery or who are not candidates for surgery. The estimated
`number of patients who would be candidates for Korlym (mifepristone) therapy is ~5,000. For these
`patients, there are currently no approved medical therapies. The clinical development program
`consisted of 1 trial enrolling 50 patients, 30 of whom were followed in an extension trial for a
`variable duration of time. The small size and the relatively short duration of the trials precluded an
`assessment of the potential long-term complications of Korlym treatment, including retinopathy,
`endometrial hyperplasia and/or vaginal bleeding, and major adverse cardiovascular events (due to
`reductions in HDL-cholesterol associated with Korlym [mifepristone] use). These adverse events
`will be collected using enhanced pharmacovigilance. The purpose of the drug use PMR is to
`provide a denominator for these adverse events to see if reporting rates in the Korlym-treated
`population exceed the background incidence rates in the Cushing’s population.
`
`
`2. Describe the particular review issue and the goal of the study/clinical trial. If the study/clinical trial is
`a FDAAA PMR, describe the risk. If the FDAAA PMR is created post-approval, describe the “new
`safety information.”
`
`PMR/PMC Development Template
`
`Last Updated 2/13/2012
`
`Page 1 of 3
`
`Reference ID: 3088503
`
`

`

`Potential adverse events associated with long-term exposure to Korlym (mifepristone) include
`endometrial hyperplasia and/or vaginal bleeding, retinopathy, and major adverse cardiovascular
`events, due to observed reductions in HDL-cholesterol. Because of the small size and short duration
`of the clinical trials, a determination regarding these risks could not be made. The drug use PMR
`will provide a denominator for the adverse events and will provide information on dose, duration of
`use of the product, patient age, patient gender, indication for treatment, and prescriber specialty.
`
`
`
`3. If the study/clinical trial is a PMR, check the applicable regulation.
`If not a PMR, skip to 4.
`- Which regulation?
` Accelerated Approval (subpart H/E)
` Animal Efficacy Rule
` Pediatric Research Equity Act
` FDAAA required safety study/clinical trial
`- If the PMR is a FDAAA safety study/clinical trial, does it: (check all that apply)
` Assess a known serious risk related to the use of the drug?
` Assess signals of serious risk related to the use of the drug?
` Identify an unexpected serious risk when available data indicate the potential for a serious
`risk?
`
`- If the PMR is a FDAAA safety study/clinical trial, will it be conducted as:
` Analysis of spontaneous postmarketing adverse events?
`Do not select the above study/clinical trial type if: such an analysis will not be sufficient to
`assess or identify a serious risk
`
`
`
` Analysis using pharmacovigilance system?
`Do not select the above study/clinical trial type if: the new pharmacovigilance system that the
`FDA is required to establish under section 505(k)(3) has not yet been established and is thus
`not sufficient to assess this known serious risk, or has been established but is nevertheless not
`sufficient to assess or identify a serious risk
`
` Study: all other investigations, such as investigations in humans that are not clinical trials as
`defined below (e.g., observational epidemiologic studies), animal studies, and laboratory
`experiments?
`Do not select the above study type if: a study will not be sufficient to identify or assess a
`serious risk
`
`
`
`
`
` Clinical trial: any prospective investigation in which the sponsor or investigator determines
`the method of assigning investigational product or other interventions to one or more human
`subjects?
`4. What type of study or clinical trial is required or agreed upon (describe and check type below)? If the
`study or trial will be performed in a subpopulation, list here.
`A drug utilization study to provide the following information about users of Korlym (mifepristone):
`age, gender, dose, duration of use, indication for treatment, and prescriber specialty.
`
`PMR/PMC Development Template
`
`Last Updated 2/13/2012
`
`Page 2 of 3
`
`Reference ID: 3088503
`
`

`

`
`Required
` Observational pharmacoepidemiologic study
` Registry studies
` Primary safety study or clinical trial
` Pharmacogenetic or pharmacogenomic study or clinical trial if required to further assess safety
` Thorough Q-T clinical trial
` Nonclinical (animal) safety study (e.g., carcinogenicity, reproductive toxicology)
`Continuation of Question 4
`
`
` Nonclinical study (laboratory resistance, receptor affinity, quality study related to safety)
` Pharmacokinetic studies or clinical trials
` Drug interaction or bioavailability studies or clinical trials
` Dosing trials
` Additional data or analysis required for a previously submitted or expected study/clinical trial
`(provide explanation)
`
` Meta-analysis or pooled analysis of previous studies/clinical trials
` Immunogenicity as a marker of safety
` Other (provide explanation)
`Drug utilization study
`
`Agreed upon:
` Quality study without a safety endpoint (e.g., manufacturing, stability)
` Pharmacoepidemiologic study not related to safe drug use (e.g., natural history of disease,
`background rates of adverse events)
` Clinical trials primarily designed to further define efficacy (e.g., in another condition,
`different disease severity, or subgroup) that are NOT required under Subpart H/E
` Dose-response study or clinical trial performed for effectiveness
` Nonclinical study, not safety-related (specify)
`
` Other
`
`
`
`
`
`5. Is the PMR/PMC clear, feasible, and appropriate?
` Does the study/clinical trial meet criteria for PMRs or PMCs?
` Are the objectives clear from the description of the PMR/PMC?
` Has the applicant adequately justified the choice of schedule milestone dates?
` Has the applicant had sufficient time to review the PMRs/PMCs, ask questions, determine
`feasibility, and contribute to the development process?
`
`
`PMR/PMC Development Coordinator:
` This PMR/PMC has been reviewed for clarity and consistency, and is necessary to further refine
`the safety, efficacy, or optimal use of a drug, or to ensure consistency and reliability of drug
`quality.
`
`
`_______________________________________
`(signature line for BLAs)
`
`PMR/PMC Development Template
`
`Last Updated 2/13/2012
`
`Page 3 of 3
`
`Reference ID: 3088503
`
`

`

`PMR/PMC Development Template
`
`
`This template should be completed by the PMR/PMC Development Coordinator and included for each
`PMR/PMC in the Action Package.
`
`
`NDA #/Product Name:
`
`PMR/PMC Description:
`
`202107/Korlym (mifepristone)
`A drug-drug interaction clinical trial to determine a quantitative estimate of
`the change in exposure of mifepristone following co-administration with
`ketoconazole (a strong CYP3A4 inhibitor).
`
` 08/18/2012
` 05/18/2013
` 08/18/2013
`
`
`
`
`PMR/PMC Schedule Milestones: Final Protocol Submission:
`
`Study/Trial Completion:
`
`Final Report Submission:
`
`Other:
`
`
`1. During application review, explain why this issue is appropriate for a PMR/PMC instead of a
`pre-approval requirement. Check type below and describe.
` Unmet need
` Life-threatening condition
` Long-term data needed
` Only feasible to conduct post-approval
` Prior clinical experience indicates safety
` Small subpopulation affected
` Theoretical concern
` Other
`
`
`
`Endogenous Cushing’s syndrome is a rare disorder (~20,000 patients with Cushing’s
`syndrome in the U.S.). The indication for Korlym (mifepristone) is for the control of
`hyperglycemia due to hypercortisolism in adult patients with endogenous Cushing’s syndrome
`who have type 2 diabetes or glucose intoler

This document is available on Docket Alarm but you must sign up to view it.


Or .

Accessing this document will incur an additional charge of $.

After purchase, you can access this document again without charge.

Accept $ Charge
throbber

Still Working On It

This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.

Give it another minute or two to complete, and then try the refresh button.

throbber

A few More Minutes ... Still Working

It can take up to 5 minutes for us to download a document if the court servers are running slowly.

Thank you for your continued patience.

This document could not be displayed.

We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.

Your account does not support viewing this document.

You need a Paid Account to view this document. Click here to change your account type.

Your account does not support viewing this document.

Set your membership status to view this document.

With a Docket Alarm membership, you'll get a whole lot more, including:

  • Up-to-date information for this case.
  • Email alerts whenever there is an update.
  • Full text search for other cases.
  • Get email alerts whenever a new case matches your search.

Become a Member

One Moment Please

The filing “” is large (MB) and is being downloaded.

Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.

Your document is on its way!

If you do not receive the document in five minutes, contact support at support@docketalarm.com.

Sealed Document

We are unable to display this document, it may be under a court ordered seal.

If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.


Access Government Site

We are redirecting you
to a mobile optimized page.





Document Unreadable or Corrupt

Refresh this Document
Go to the Docket

We are unable to display this document.

Refresh this Document
Go to the Docket