CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208082Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 208082
`
`SUPPL #
`
`HFD # 120
`
`Trade Name Austedo
`
`Generic Name deutetrabenazine tablets
`
`Applicant Name Teva Pharmaceuticals USA, Inc.
`
`Approval Date, If Known 4/3/ 1 7 (PDUFA)
`
`PART I
`
`IS AN EXCLUSIVITY DETERNIINATION NEEDED?
`
`1. An exclusivity determination Will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes"
`to one or more of the following questions about the submission.
`
`a) Is it a 505(b)(1), 505(b)(2) or efficacy supplement?
`
`YES|XI
`
`NO|:|
`
`Ifyes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(2)
`
`b) Did it require the review of clinical data other than to support a safety claim or change
`in labeling related to safety?
`(If it
`required review only of bioavailability or
`bioequivalence data, answer "no."
`
`YES E
`
`NO D
`
`If your answer is "no" because you believe the study is a bioavailability study and,
`therefore, not eligible for exclusivity, EXPLAIN why it
`is a bioavailability study,
`including your reasons for disagreeing with any arguments made by the applicant that the
`
`study was not simply a bioavailability study.
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`Reference ID: 4078065
`
`Page 1
`
`

`

`c) Did the applicant request exclusivity?
`
`YES g]
`
`NO |:|
`
`Ifthe answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`5 years
`
`(I) Has pediatric exclusivity been granted for this Active Moiety?
`YES [:|
`
`NO E
`
`If the answer to the above question in YES, is this approval a result of the studies submitted
`in response to the Pediatric Written Request?
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY
`TO THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`YES|:]
`
`NOE
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE
`BLOCKS ON PAGE 8 (even if a study was required for the upgrade).
`
`PART II
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingedient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the
`same active moiety as the drug under consideration? Answer "yes" if the active moiety
`(including other esterified forms, salts, complexes, chelates or clathrates) has been previously
`approved, but this particular form of the active moiety, e.g., this particular ester or salt (including
`salts with hydrogen or coordination bonding) or other non—covalent derivative (such as a
`complex, chelate, or clathrate) has not been approved. Answer "no" if the compound requires
`metabolic conversion (other than deesterification of an esterified form of the drug) to produce an
`already approved active moiety.
`
`YES|:]
`
`N0|z
`
`Reference ID: 4078065
`
`Page 2
`
`

`

`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`NDA#
`
`NDA#
`
`NDA#
`
`2. Combination product.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA
`previously approved an application under section 505 containing y y of the active moieties
`in the drug product? If, for example, the combination contains one never-before-approved active
`moiety and one previously approved active moiety, answer "yes."
`(An active moiety that is
`
`marketed under an OTC monograph, but that was never approved under an NDA, is considered
`not previously approved.)
`
`YES |:|
`
`NO E]
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`NDA#
`
`NDA#
`
`NDA#
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART II IS "NO," GO DIRECTLY TO
`THE SIGNATURE BLOCKS ON PAGE 8.
`(Caution: The questions in part II of the summary
`should only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEIVIENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of
`new clinical investigations (other than bioavailability studies) essential to the approval of the
`
`application and conducted or sponsored by the applicant." This section should be completed only
`if the answer to PART II, Question 1 or 2 was "yes."
`
`Reference ID: 4078065
`
`Page 3
`
`

`

`(The Agency interprets
`1. Does the application contain reports of clinical investigations?
`"clinical investigations" to mean investigations conducted on humans other than bioavailability
`studies.) Ifthe application contains clinical investigations only by virtue of a right of reference to
`clinical investigations in another application, answer "yes," then skip to question 3(a).
`If the
`answer to 3(a) is “yes" for any investigation referred to in another application, do not complete
`remainder of smmnary for that investigation.
`
`YES
`
`|:|
`
`NO |:|
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved
`the application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical
`trials, such as bioavailability data, would be sufficient to provide a basis for approval as an
`ANDA or 505(b)(2) application because of what is already known about a previously approved
`product), or 2) there are published reports of studies (other than those conducted or sponsored by
`
`the applicant) or other publicly available data that independently would have been sufficient to
`support approval of the application, without reference to the clinical investigation submitted in
`the application.
`
`investigation (either
`is a clinical
`(a) In light of previously approved applications,
`conducted by the applicant or available from some other source, including the published
`literature) necessary to support approval of the application or supplement?
`YES [:|
`
`NO D
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`(b) Did the applicant submit a list of published studies relevant to the safety and
`effectiveness of this drug product and a statement that the publicly available data would
`not independently support approval of the application?
`
`YES D NO D
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to
`disagree with the applicant's conclusion? Ifnot applicable, answer NO.
`
`YES|:]
`
`NO|:|
`
`Ifyes, explain:
`
`Reference ID: 4078065
`
`Page 4
`
`

`

`(2) Ifthe answer to 2(b) is "no," are you aware of published studies not conducted
`or sponsored by the applicant or other publicly available data that
`could
`independently demonstrate the safety and effectiveness of this drug product?
`
`YES|:]
`
`NO|:|
`
`If yes, explain:
`
`(c)
`
`If the answers to (b)(l) and (b)(2) were both "no," identify the clinical
`investigations submitted in the application that are essential to the approval:
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`In addition to being essential, investigations must be "new" to support exclusivity. The
`3.
`agency interprets "new clinical investigation" to mean an investigation that 1) has not been relied
`on by the agency to demonstrate the effectiveness of a previously approved drug for any
`indication and 2) does not duplicate the results of another investigation that was relied on by the
`agency to demonstrate the effectiveness of a previously approved drug product, i.e., does not
`redemonstrate something the agency considers to have been demonstrated in an already approved
`application.
`
`a) For each investigation identified as "essential to the approval," has the investigation
`been relied on by the agency to demonstrate the effectiveness of a previously approved
`drug product?
`(If the investigation was relied on only to support the safety of a
`previously approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`YES |:|
`
`NO [I
`
`YES |:|
`
`NO D
`
`If you have answered "yes" for one or more investigations,
`
`identify each such
`
`investigation and the NDA in which each was relied upon:
`
`b) For each investigation identified as "essential to the approval", does the investigation
`
`Reference ID: 4078065
`
`Page 5
`
`

`

`duplicate the results of another investigation that was relied on by the agency to support
`the effectiveness of a previously approved drug product?
`
`Investigation #1
`
`Investigation #2
`
`YES |:|
`
`NO |:|
`
`YES |:|
`
`NO D
`
`If you have answered "yes" for one or more investigation, identify the NBA in which a
`similar investigation was relied on:
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the
`application or supplement that is essential to the approval (i.e., the investigations listed in
`
`#2(c), less any that are not "new" :
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored
`by" the applicant if, before or during the conduct of the investigation, 1) the applicant was the
`sponsor of the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or
`its predecessor in interest) provided substantial support for the study. Ordinarily, substantial
`support will mean providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(c): if the investigation was
`carried out under an 1ND, was the applicant identified on the FDA 1571 as the sponsor?
`
`! !
`
`! NO |:|
`! Explain:
`
`! !
`
`! NO |:|
`! Explain:
`
`Investigation #1
`
`IND #
`
`YES E]
`
`Investigation #2
`
`1ND #
`
`YES |:]
`
`Reference ID: 4078065
`
`Page 6
`
`

`

`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`interest provided substantial support for the study?
`
`! !
`
`! NO |:|
`! Explain:
`
`! !
`
`! NO |:|
`! Explain:
`
`Investigation #1
`
`YES |:|
`Explain:
`
`Investigation #2
`
`YES |:]
`Explain:
`
`(c) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to
`the drug are purchased (not just studies on the drug), the applicant may be considered to
`have sponsored or conducted the studies sponsored or conducted by its predecessor in
`interest.)
`
`YES|:|
`
`NO|:|
`
`Ifyes, explain:
`
`
`
`Name of person completing form: Stacy Metz, Phann D
`Title: Senior Regulatory Project Manager
`Date: 3/31/17
`
`Reference ID: 4078065
`
`Page 7
`
`

`

`
`Name of Office/Division Director signing form:
`Deputy Director
`Title:
`
`Eric Bastings, MD
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 4078065
`
`Page 8
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`STACY M METZ
`03/31/2017
`
`ERIC P BASTINGS
`04/01/2017
`
`Reference ID: 4078065
`
`

`

`ACTION PACKAGE CHECKLIST
`
`
`
`NDA Supplement #
`BLA Supplement #
`
`IfNDA. Efficacy Supplement Type:
`(an action package is not requiredfor SE8 or SE9 supplements)
`
`
`
`
`NDA # 208082
`BLA #
`
`
` Proprietary Name: Austedo
`
`Applicant: Teva Pharmaceuticals USA, Inc.
`Established/Proper Name: deutetrabenazine
`
`
`Dosage Form:
`Oral Tablet
`Agent for Applicant (if applicable): Christine Schulteis
`
`
`Division: DNP
`
`
`For ALL 505
`lication two months
`2 a
`rior to EVERY action:
`
`
`
`
`
`
`
`
`RPM: Stacy Metz
`
`NDA Application Type: D 505(b)(l) E 505(b)(2)
`Efficacy Supplement:
`E] 505(b)(1)
`|:| 505(b)(2)
`
`|:| 351(a)
`BLA Application Type: E] 351(k)
`Efficacy Supplement:
`[:I 351(k) D 351(a)
`
`
`
`
`
`
`
`
`
`
`
`0 Review the information in the 505(b)(2) Assessment and submit
`the draft2 to CDER 0ND 10 for clearance.
`
`0 Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
`E No changes
`E] New patent/exclusivity (nonfi CDER 0ND 10)
`Date of check:
`
`
`
`
`Note: Ifpediatric exclusivity has been granted or the pediatric
`information in the labeling ofthe listed drug changed, determine whether
`pediatric information needs to be added to or deletedfrom the labeling of
`this drug.
`
`User Fee Goal Date is 4/3/17
`E AP D TA DCR
`
`
`Previous actions (specifir type and datefor each action taken)
`
`E] None CR 5/29/16
`
`If accelerated approval or approval based on efficacy studies in animals. were promotional
`materials received?
`
`Note: Promotional materials to be used within 120 days after approval must have been
`submitted (for exceptions. see
`http://“vv' fda.gov/downloads/Drugs/GuidanceC omplianc eRegulatmylnfonnation/Guida
`nces/uc111069965.
`. Ifnot submitted. ex lain
` Application Characteristics 3
`
`1 The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 2) lists
`the documents to be included in the Action Package.
`2 For resubmissions. 505(b)(2) applications must be cleared before the action. but it is not necessary to resubmit the draft 505(b)(2)
`Assessment to CDER 0ND 10 unless the Assessment has been substantively revised (e.g.. new listed drug. patent certification
`revised).
`3 Answer all questions in all sections in relation to the pending application. i.e.. if the pending application is an NDA or BLA
`supplement. then the questions should be answered in relation to that supplement. not in relation to the original NDA or BLA.
`
`Version: 2/12/16
`
`Reference ID: 408031 0
`
`

`

`NDA/BLA #
`
`Page 2
`
`Review priority: 8 Standard El Priority
`Chemical classification (new NDAs only):
`(confirm chemical classification at time ofapproval)
`
`I] Fast Track
`I] Rolling Review
`E Orphan drug designation
`[:I Breakthrough Therapy designation
`(NOIE: Set the submission property in DARRTS' and notify the CDER Breakthrough Therapy Program Manager;
`Refer to the “
`1M 81' Checklistfor Considerations after Designation Granted”for other required actions: CST SharePoint)
`
`I] Rx-to-OTC full switch
`D Rx-to-OTC partial switch
`D Direct-to-OTC
`
`NDAs: Subpart H
`D Accelerated approval (21 CFR 314.510)
`[I Restricted distribution (21 CFR 314.520)
`Subpart I
`D Approval based on animal studies
`
`BLAs: Subpart E
`[:I Accelerated approval (21 CFR 601.41)
`E] Restricted distribution (21 CFR 601.42)
`Subpart H
`D Approval based on animal studies
`
`D Submitted in response to a PMR
`I] Submitted in response to a PMC
`I] Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: E MedGuide
`I] Communication Plan
`E] ETASU
`E MedGuide w/o REMS
`E REMS not required
`
`'3' BLAs only: Is the product subject to ofiicial FDA lot release per 21 CFR 610.2
`(approvals only)
`
`D Yes D No
`
`'3' Public communications (approvals only)
`
`0 Ofiice of Executive Programs (OEP) liaison has been notified of action
`
`E Yes [:I No
`
`.
`.
`.
`.
`.
`Indicate what types (if any) of information were issued
`
`0
`
`I] None
`I] FDA Press Release
`D FDA Talk Paper
`D CDER Q&As
`E Other Social Media (twitter. c
`
`0:0 Exclusivity
`
`0
`
`0
`
`Is approval of this application blocked by any type of exclusivity (orphan. 5-year
`NCE. 3-year. pediatric exclusivity)?
`Ifso.si
`the pe
`
`E No
`
`D Yes
`
`.20 Patent Information (NDAs only)
`
`0
`
`Patent Information:
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`which approval is sought.
`
`E Verified
`I] Not applicable because drug is
`an old antibiotic.
`
`
`
`
`
` o
`
`0.0
`List of officers/employees who participated in the decision to approve this application and
`
`consented to be identified on this list (approvals only) M Included
`
`Documentation of consent/non—consent by officers/employees
`
`E Included
`
`Reference ID: 408031 0
`
`

`

`NDA/BLA #
`
`Page 3
`
`O
`0.. Copies of all action letters (including approval letter withfinal labeling)
`
`
`
`
`Action(s) and date(s) CR 5/27/16 :
`
`
`
`
`O
`0.. Package Insert (write submission/comnmnication date at upper light offirstpage ofPI)
`
`E Included
`
`0 Most recent draft labeling (ifit is division-proposed labeling, it should be in
`track—chum es ormat)
`0 Original applicant-proposed labeling
`
`0? Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirstpage ofeach piece)
`
`
`
`E Included
`
`E Medication Guide
`E Patient Package Insert
`D Instructions for Use
`D Device Labeling
`
`
`
`E Included
`0 Most-recent drafi labeling (ifit is division-proposed labeling, it should be in
`track—changesformat)
`0 Original applicant-proposed labeling
`E Included
`
`6° Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper light offirstpage ofeach submission)
`0 Most-recent draft labeling
`
`I Inpnetary Name
`Acceptability/non-acceptability letter(s) (indicate date(s))
`0
`Review(s) (indicate date(s)
`
`O
`0.9
`
`Labeling reviews (indicate dates ofreviews)
`
`E Incl
`
`7/2/15 and 1/12/17
`6,22/15 and “10/17
`
`RPM: |:| None 8/6/15
`DMEPA: I] None 10/30/112
`
`DMPP/PLT (DRISK):
`E] None 7/12/16 and E
`
`OPDP: El None 6/6/16 and E
`
`SEALD: E None
`CSS: E None
`Product Quality D None see t
`
`Other: I None
`
`
`
`7/17/1 5 Filing Meeting
`5/24/16 Filing Review at
`
`0O0.90..
`
`RPM Filing Review‘lMemo of Filing Meeting (indicate date ofeach review)
`All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`[I Not a (b)(2)
`
`cleared 5/27/16 :
`
`Q
`0.. NDAs only: Exclusivity Summary (signed by Division Directoz)
`
`E Included
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Reference ID: 408031 0
`
`
`
`

`

`NDA/BLA #
`
`Page 4
`
`°§° Application Integrity Policy (AIP) Status and Related Documents
`
`http://“MW fda. gov/ICECI/EnforcementActions/ApplicationlnteglityPolicy/default.htm
`
`Applicant is on the AIP
`
`This application is on the AIP
`
`[I Yes X No
`
`I] Yes E No
`
`o
`
`0
`
`If yes. Center Director’s Exception for Review memo (indicate date)
`
`If yes. 0C clearance for approval (indicate date ofclearance
`communication)
`
`[:I Not an AP action
`
`Pediatrics (approvals only)
`Date reviewed by PeRC
`IfPeRC review not necessary. explain: Orphan Designation
`
`Breakthrough Therapy Designation
`
`IX N/A
`
`Breakthrough Therapy Designation Letter(s) (granted. denied. an/or rescinded)
`
`CDER Medical Policy Council Breakthrough Therapy Designation
`Determination Rew'ew Template(s) (include only the completed template(s) and
`not the meetin minutes)
`
`CDER Medical Policy Council Brief — Evaluating a Breakthrough Therapy
`Designation for Rescission Template(s) (include only the completed template(s)
`and not the meeting mitmtes)
`
`(completed CDER 11ch templates can befound in DARRTS as clinical reviews or on
`the MPC' SlIarePoint Site
`
`Outgoing communications: letters. emails. and faxes considered important to include in
`the action package by the reviewing office/division (e.g.. clinical SPA letters. RTF letter.
`Formal Dispute Resolution Request decisional letters. etc.) (do not include OPDP letters
`regardingpre—launch promotional materials as these are non—disclosable; do not include
`Master File letters; do not include previous action letters, as these are located elsewhere
`in tacka e)
`Internal documents: memoranda. telecons. emails. and other documents considered
`
`important to include in the action package by the reviewing office/division (e.g..
`Re-
`.to Briefin - minutes. Medical Polic Council meetin- minutes
`
`Minutes of Meetings
`
`O
`0..
`
`O
`0.0
`
`O
`0.0
`
`O
`0..
`
`0
`0..
`
`
`
`
`If not the first review cycle. any end-of—review meeting (indicate date ofmtg)
`
`D N/A or no mtg
`
`10/18/16
`
`Pre-NDA/BLA meeting (indicate date ofmtg)
`
`EOP2 meeting (indicate date ofmtg)
`
`Mid-cycle Communication (indicate date ofmtg)
`
`Late-cycle Meeting (indicate date ofmtg)
`
`E] Nomtg 4/17/15
`
`D No mtg
`
`12/26/12
`
`D N/A 12/2/15
`
`E] N/A 3/21/16
`
`Other milestone meetings (e.g.. EOP2a. CMC focused milestone meetings)
`(indicate dates 0 mt_ s)
`
`Reference ID: 4080310
`
`

`

`NDA/BLA #
`
`Page 5
`
`0? Advisory Committee Meeting(s)
`
`E No AC meeting
`
`0 Date(s) of Meeting(s)
`
`4° Oflice Director Decisional Memo (indicate datefor each review)
`
`[I None
`
`5/27/16 and 4/3/17
`
`Division Director Summary Review (indicate datefor each review)
`
`[I None
`
`5/27/16 and 3/29/17
`
`Cross-Discipline Team Leader Review (indicate datefor each review)
`
`I] None
`
`5/24/16 and 3/28/ 17
`
`PMR/PMC Development Templates (indicate total number)
`
`E None
`
`5/24/16 and 3/28/17
`
`
`
`9..
`
`Clinical Reviews
`
`0
`
`0
`
`0
`
`0
`
`Clinical Team Leader Review(s) (indicate datefor each review)
`
`E No separate review
`
`Clinical review(s) (indicate datefor each review)
`
`5/24/16 and 3/28/17
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`I] None
`
`°1° Financial Disclosure reviews(s) or location/date if addressed in another review
`OR
`If no financial disclosure information was required. check here I] and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`.
`.
`.
`.
`see chmcal primary rev1ew
`
`4° Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)5
`0
`0..
`
`Controlled Substance Staff review(s) and Scheduling Recommendation (indicate date of
`each review)
`
`E None
`
`E] N/A 7/30/15, 3/8/16 and 1
`
`’1' Risk Management
`0
`REMS Docmnents and REMS Supporting Document (indicate date(s) of
`submission(s))
`REMS Memo(s) and letteifs) (indicate date(s))
`Risk management review(s) and recommendations (including those by OSE and
`CSS) (indicate date ofeach review and indicate location/date ifincmporated
`into another review)
`
`9
`0.9
`
`E] None 5/2/16 and 4/3/17
`
`
`
`
`081 Clinical Inspection Review Summary(ies) (include copies of08] letters to
`im‘estigators)
`
`El None requested 2/22/16
`
`K4
`
`’1' Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`
`I] No separate review
`
`Clinical Microbiology Review(s) (indicate datefor each review)
`
`I] None
`
`I
`
`6° Statistical Division Director Review(s) (indicate datefor each review)
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`Statistical Team Leader Review(s) (indicate datefor each review)
`
`E No separate review
`
`E No separate review
`
`Statistical Review(s) (indicate datefor each review)
`
`E] None
`
`2/19/16
`
`5 For Part 3 combination products. all reviews from the reviewing Center(s) should be entered into the official archive (for timber
`instructions. see “Section 508 Compliant Documents: Process for Regulatory Project Managers” located in the CST electronic
`repository).
`
`Reference ID: 408031 0
`
`

`

`NDA/BLA #
`
`Page 6
`
`6° Clinical Pharmacology Division Director Review(s) (indicate datefor each review)
`
`Clinical Pharmacology Team Leader Review(s) (indicate datefor each review)
`
`Clinical Pharmacology review(s) (indicate datefor each review)
`
`
`I
`
`'1' 081 Clinical Pharmacology Inspection Review Summary (include copies of081 letters)
`
`
`0 ADP/T Review(s) (indicate datefor each review)
`
`E] No separate rev1ew 5/24/16 :
`
`O
`0.9 Pharmacology/Toxicology Discipline Reviews
`
`
`
`Supervisory Review(s) (indicate datefor each review)
`0
`fmtox rev1ew(s). mcludmg referenced IND revrews (indicate datefor each
`0
`°3° Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`_
`for each review)
`
`I] No separate review 3/31/16
`C] None
`2/4/16 and 1/18/17
`
`E None
`
`'1' Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`E No care
`
`-
`I.
`. ECAC/CAC report/memo of meeting
`
`E None
`Included in Pfl' review. a _ e
`
`4° OSI Nonclinical Inspection Review Summary (include copies of051 letters)
`
`E None requested
`
`I
`
`
`6° Product Quality Discipline Reviews6
`
`0
`
`0
`
`Tertiary review (indicate datefor each review)
`
`Secondary review (e.g.. Branch Chief) (indicate datefor each review)
`
`X None
`
`E None
`
`0
`
`Integrated Quality Assessment (contains the Executive Summary and the primary
`.
`.
`.
`.
`.
`.
`revrews from each product quahty revrew disc1phne) (indicate datefor each
`review)
`9
`0.0 Reviews by other disciplines/divisions/Centers requested by product quality review team
`(indicate date ofeach review)
`0
`9.. Environmental Assessment (check one) (original and supplemental applications)
`
`El None
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`4/
`
`/
`.
`/ 4/
`18 16 5 2
`
`16 and
`
`.
`.-
`
`E None
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`8 Categorical Exclusion (indicate review date)(all original applications and
`all eflicacy supplements that could increase thepatientpopulation)
`
`see CMC Revrew 3,7,”
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`[3 Review & FONSI (indicate date of review)
`
`[:I Review & Environmental Impact Statement (indicate date ofeach review)
`
`9
`0.9 Facilities Review/Inspection
`
`table
`8 Facilities inspections (action must be taken prior to the re-evaluation date) (only E Acc
`original applications and eflicacv supplements that require a mamg’acturing
`Re-evalgtion date'
`facility inspection(e.g., new strength, manufacturingprocess, or manufacturing
`El Withhold reco
`site change)
`I Not applicable
`
`endation
`
`
`
`
`6 Do not include Master File (IVIF) reviews or communications to IMF holders. However. these documents should be made available
`upon signatory request.
`
`Reference ID: 408031 0
`
`

`

`
`
`NDA/BLA #
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`Page 7
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`-
`-
`o:- For all 505(b)(2) apphcations:
`0 Check Orange Book for newly listed patents and/or exclusivity (including
`.
`.
`.
`.
`pedratnc exclusrvrty)
`
`
`han es
`.
`_
`.
`E No c
`g
`.
`Iggeggilgexcmmw (Nonfi
`)
`
`0
`Finalize 505(b)(2) assessment
`E Done
`
`
` 0
`
`E] Done
`°2° For Breakthrough Therapy (BT) Designated drugs:
`(Send email to CDER 0ND 10)
`0 No I
`the CDER BT Pro :4 .
`I Mana ' er
`O
`0.0 For products that need to be added to the flush list (generally opioids): Flush List D Done
`0 Notify the Division of Online Communications, Oflice of Communications
`9.. Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`email
`0
`0.0
`
`Ifan FDA communication will issue, notify Press Office of approval action afier
`confirming that applicant received courtesy copy of approval letter
`
`E Done
`
`E Done
`
`O
`0.0
`
`Ensure that proprietary name. if any, and established name are listed in the
`Application Product Names section of DARRTS. and that the proprietary name is E Done
`
`identified as the “preferred” name
`'3 Ensure Pediatric Record is accurate
`
`E Done
`
`02° Send approval email within one business day to CDER-APPROVALS
`
`E Done
`
`
`
`Reference ID: 4080310
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`STACY M METZ
`04/05/2017
`
`Reference ID: 4080310
`
`

`

`From:
`To:
`Subject:
`
`Date:
`Attachments:
`
`Metz, Stacy
`Metz, Stacy
`FW: NDA 208082 Resubmission to CR/Austedo (deuterated tetrabenazine) in Huntington"s disease--Orphan
`Designation
`Friday, March 31, 2017 3:52:02 PM
`05 Nov 2014 - Letter from FDA Granting Orphan Designation for Huntingto....pdf
`
`-----Original Message-----
`From: PeRC
`Sent: Thursday, November 17, 2016 1:39 PM
`To: Metz, Stacy
`Subject: RE: NDA 208082 Resubmission to CR/Austedo (deuterated tetrabenazine) in Huntington's
`disease--Orphan Designation
`
`Thanks Stayce-
`
`No additional information is needed at this time.
`
`Meshaun
`
`-----Original Message-----
`From: Metz, Stacy
`Sent: Thursday, November 17, 2016 12:10 PM
`To: PeRC
`Subject: NDA 208082 Resubmission to CR/Austedo (deuterated tetrabenazine) in Huntington's disease--
`Orphan Designation
`Importance: High
`
`Hello.
`
`DNP received an NDA resubmission to a CR for a Huntington's disease product on 10/3/16 with PDUFA
`of 4/3/16.
`
`NDA 208082: will not trigger PREA because the application has an Orphan designation. I have attached
`the orphan designation letter.
`EDR Location: \\CDSESUB1\evsprod\NDA208082\208082.enx
`
`Please let me know if you need anything else.
`Thanks!
`Stacy
`
`Reference ID: 4078400
`
`

`

`-‘.
`
`Public Health Service
`DEPARTMENT OF HEALTH 8- HUMAN SERVICES
`
`
`Office of Orphan Products Development
`Food and Drug Administration
`10903 New Hampshire Avenue
`WO32- 5295
`
`Silver Spring, MD 20993
`
`NOV 0 5 2014
`
`Hyman, Phelps & McNamara, RC.
`700 Thirteenth Street, NW.
`Suite 1200
`
`Washington, DC. 20005-5929
`
`Attention:
`
`Kurt R. Karst
`
`US Regulatory Representative
`
`Re: Designation Request # 12-3832
`Amendment dated:
`Amendment received:
`
`September 8, 2014
`September 10,2014
`
`Dear Mr. Karst:
`
`This letter responds to your amended request submitted on behalf of Auspex
`Pharmaceuticals for orphan-drug designation of dé-teuabenazine (also referred to as: SD-
`809 and deutrabenazine) for “treatment of chorea associated with Huntington’s disease."
`
`Pursuant to section 526 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bb),
`your orphan-drug designation requth of ds-tetrabenazine (deutrabenazine) is granted for
`treatment ofHuntington 's disease. Please note that the designation granted is broader than
`the indication proposed in your designation request. Please be advised that it is the active
`moiety or principal molecular structural features of the drugl and not the formulation of the
`drug that is designated.
`
`If your drug receives marketing approval for an indication broader than what is designated,
`it may not be entitled to exclusive marketing rights under section 527 (21 U.S.C. 360cc).
`Therefore, prior to submission of your marketing application, we mqmt that you compare
`the drug’s orphan designation with the proposed marketing indication and submit additional
`information to amend the orphan-drug designation if warranted. 21 CFR 316.26
`
`' The term “drug" in this letter includes drug and biological products.
`
`Reference ID: 4082538
`
`

`

`
`
`
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`Hyman, Phelps & McNamara, RC.
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`2
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`If the same drug is approved for the same orphan indication before you obtain marketing
`
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`approval of your drug, you will have to demonstrate that your drug is clinically superior to
`
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`the already approved same drug in order to obtain orphan-drug exclusivity. Failure to
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`demonstrate clinical superiority over the already approved same drug will result in your
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`drug not receiving orphan-drug exclusivity. 21 CFR 316.34(c)
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`You must submit to the Office of Orphan Products Development a brief progress report of
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`drug development within 14 months after this date and annually thereafter until marketing
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`approval. 21 CFR 316.30
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`Please notify this Office within 30 days of submitting a marketing application for the drug’s
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`designated use. Once your marketing application is approved, please contact Stephanie
`
`
`
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`
`
`
`
`
`
`
`Donahoe, RPh, MPH,Vat 301-796-8681 or alternatively at 301-796-8660 to assess eligibility
`
`
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`for orphanvdrug exclusivity.
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`If you have questions regarding the development of your designated product, please feel
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`
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`free to contact John D. Milto, MD, at 301-796-8687 or alternatively at 301496-8660.
`
`
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`
`
`Congratulations on obtaining your orphan-drug designation.
`
`Sincerely,
`
`
`
`
`
`
`A! %£%7 égam' fl €20
`
`
`
`
`
`Gaya R. Rao, MD, JD
`
`Director
`
`
`
`
`Office of Orphan Products Development
`
`
`
`
`
`Reference ID: 4082538
`Reference ID: 4082538
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`STACY M METZ
`03/31/2017
`
`Reference ID: 4078400
`
`

`

`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`PROPRIETARY NAME REQUEST
`CONDITIONALLY