CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`208341Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 208341
`
`SUPPL #
`
`HFD #
`
`Trade Name EPCLUSA
`
`Generic Name sofosbuvir and velpatasvir fixed dose combination tablet
`
`Applicant Name Gilead Sciences
`
`
`
`Approval Date, If Known June 28, 2016
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION 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
`
`NO
`
`If yes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`505(b)(1)
`
`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
`
`NO
`
`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: 3950816
`
`Page 1
`
`

`

`c) Did the applicant request exclusivity?
`
` YES
`
`NO
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`5 years
`
`d) Has pediatric exclusivity been granted for this Active Moiety?
` YES
`
`NO
`
` 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
`
`NO
`
`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).
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`PART II
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient 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
`
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`Reference ID: 3950816
`
`Page 2
`
`

`

`
`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 any one 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
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, if known, the
`NDA #(s).
`
`NDA# 204671
`NDA# 205834
`NDA#
`
`Sovaldi (sofosbuvir)
`Harvoni (sofosbuvir and ledipasvir)
`
`
`NDA 208341 contains velpatasvir, a new chemical entity, in combination with sofosbuvir, a
`previously approved active moiety. Under the Agency’s new interpretation described in the
`Agency’s Guidance for Industry, New Chemical Entity Exclusivity for Certain Fixed-
`Combination Drug Products, a drug substance is eligible for 5-year exclusivity, provided it
`meets the regulatory definition of new chemical entity, regardless of whether that drug
`substance is approved in a single-ingredient drug product or in a fixed-combination with
`another drug substance that contains no previously approved active moiety, or in a fixed-
`combination with another drug substance that contains a previously approved active moiety.
`This NDA is thus eligible for 5-year new chemical entity exclusivity pursuant to the new
`interpretation.
`
`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.
`
`Reference ID: 3950816
`
`Page 3
`
`

`

`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`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."
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets
`"clinical investigations" to mean investigations conducted on humans other than bioavailability
`studies.) If the 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 summary 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.
`
`(a) In light of previously approved applications, is a clinical investigation (either
`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
`
`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
`
`NO
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to
`
`Reference ID: 3950816
`
`Page 4
`
`

`

`
`
`disagree with the applicant's conclusion? If not applicable, answer NO.
`
`
`
` YES
`
`NO
`
` If yes, explain:
`
`
`
`
`
`(2) If the 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)(1) 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.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The
`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
`
`YES
`
`
`
`NO
`
`NO
`
`Reference ID: 3950816
`
`Page 5
`
`

`

`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
`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
`
`YES
`
`NO
`
`NO
`
`If you have answered "yes" for one or more investigation, identify the NDA 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 IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`
`
`!!
`
`! NO
`! Explain:
`
`
`
`Investigation #1
`
`IND #
`
`YES
`
`
`
`Reference ID: 3950816
`
`Page 6
`
`

`

`!!
`
`
`! NO
`! Explain:
`
`
`
`(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
`
`If yes, explain:
`
`
`
`=================================================================
`
`
`Reference ID: 3950816
`
`Page 7
`
`Investigation #2
`
`IND #
`
`YES
`
`
`
`
`
`
`
`

`

`Name of person completing form: Linda C Onaga
`Title: Senior Regulatory Project Manager
`Date: June 27, 2016
`
`
`Name of Office/Division Director signing form: Debra Birnkrant, MD
`Title: Director
`
`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05; removed hidden data 8/22/12
`
`Reference ID: 3950816
`
`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/
`----------------------------------------------------
`
`LINDA C ONAGA
`06/27/2016
`
`DEBRA B BIRNKRANT
`06/27/2016
`
`Reference ID: 3950816
`
`

`

`ACTION PACKAGE CHECKLIST
`
`
`
`APPLICATION INFORMATION1
`NDA Supplement #
`If NDA, Efficacy Supplement Type:
`NDA # 208341
`(an action package is not required for SE8 or SE9 supplements)
`BLA Supplement #
`BLA #
`Proprietary Name: EPCLUSA
`Established/Proper Name: sofosbuvir and velpatasvir
`Dosage Form: tablets
`RPM: Linda C Onaga, MPH
`
`Applicant: Gilead Sciences, Inc
`Agent for Applicant (if applicable):
`
`NDA Application Type:
`Efficacy Supplement:
`
` 505(b)(1)
` 505(b)(1)
`
` 505(b)(2)
` 505(b)(2)
`
`BLA Application Type:
`Efficacy Supplement:
`
` 351(k)
` 351(k)
`
` 351(a)
` 351(a)
`
`Division: Division of Antiviral Products
`For ALL 505(b)(2) applications, two months prior to EVERY action:
`
` Review the information in the 505(b)(2) Assessment and submit
`the draft2 to CDER OND IO for clearance.
` Check Orange Book for newly listed patents and/or
`exclusivity (including pediatric exclusivity)
`
` No changes
` New patent/exclusivity (notify CDER OND IO)
`Date of check:
`
`Note: If pediatric exclusivity has been granted or the pediatric
`information in the labeling of the listed drug changed, determine whether
`pediatric information needs to be added to or deleted from the labeling of
`this drug.
`
` Actions
`Proposed action
`
` User Fee Goal Date is June 28, 2016
`Previous actions (specify type and date for each action taken)
`
` 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://www fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guida
`nces/ucm069965.pdf). If not submitted, explain
` Application Characteristics 3
`
` AP
`
` TA CR
`
` None
`
` Received
`
`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 OND IO 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: 8/13/15
`
`Reference ID: 3951969
`
`

`

`[XI Priority
`El Standard
`Review priority:
`Chemical classification (new NDAs only):
`(confirm chemical classification at time ofapproval)
`
`E Fast Track
`IXI Rolling Review
`El Orphan drug designation
`IXI Breakthrough Therapy designation
`(NOIE: Set the submission property in DARRTS and notify the CDER Breakthrough Therapy Program Manager;
`Refer to the “RPM 81' Checklistfor Considerations afier Designation Granted”for other require actions: CST SharePoint )
`
`E] Rx-to-OTC full switch
`E] Rx-to-OTC partial switch
`E] Direct-to-OTC
`
`NDAs: Subpart H
`[:I Accelerated approval (21 CFR 314.510)
`B Restricted distribution (21 CFR 3 14.520)
`Subpart I
`El Approval based on animal studies
`
`BLAs: Subpart E
`[:I Accelerated approval (21 CFR 601.41)
`|:] 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
`D Submitted in response to a Pediatric Written Request
`
`Comments:
`
`REMS: D MedGuide
`I: Communication Plan
`|:] ETASU
`[j MedGuide w/o REMS
`D REMS not required
`
`03° BLAs only: Is the product subject to oflicial FDA lot release per 21 CFR 610.2
`(approvals only)
`
`I: Yes
`
`El No
`
`{0 Public communications (approvals only)
`
`0 Office of Executive Programs (OEP) liaison has been notified of action
`
`IX Yes El No
`
`0
`
`Indicate what types (if any) of information were issued
`
`{0 Exclusivity
`
`0
`
`0
`
`Is approval of this application blocked by any type of exclusivity (orphan, 5-year
`NCE, 31-year, pediatric exclusivity)?
`Ifso,s'
`the p‘
`
`0? Patent Information (NDAs only)
`
`I:] None
`[X] FDA Press Release
`E] FDA Talk Paper
`E] CDER Q&As
`[Z Ofller HIV list serv
`
`X No
`
`[:I Yes
`
`
`
`0
`
`‘2 Verified
`Patent Information:
`I: Not a
`licable because dru is
`Verify that form FDA-3542a was submitted for patents that claim the drug for
`pp
`which approval is sought.
`g
`an old antibiotic.
`
`
`
`
`
`
`
`O
`
`
`
`°.° List of officers/employees who participated in the decision to approve this application and
`consented to be identified on this list (approvals only)
` Documentation of consent/non-consent by officers/employees
`
`Reference ID: 3951969
`
`

`

`NDA/BLA #
`
`Page 3
`
`
`
`
`.
`‘ .
`‘
`_
`_
`_
`.
`.
`a.
`0 Copies ofall action letters (including app) ma] letter Withfinal labeling)
`
`Action(s) and date(s)
`June 28, 2016
`
`
`
`
`
`03° Package Insert (write submission/communication date at upper right offirstpage ofPI)
`
`IE Included
`
`0 Most recent drafi labeling ('y’it is dh'ision-proposed labeling, it should be in
`______________________________”ackcllanswfomaf)
`' Original applicant-proposed labeling
`
`[Z Included
`
`
`
`
`
`D Medication Guide
`[E Patient Package Insert
`El Instructions for Use
`El Device Labeling
`
`I:I None
`IX] Included
`
`'2 Included
`
`[Z Included
`
`January 11, 2016
`January 8, 2016
`
`RPM: D None Dec 23, 2015
`DMEPA: D None June 8, 2016
`March 03, 2016
`DMPP/PLT (DRISK):
`D None May 20, 2016
`OPDP: D None May 13’ 2016
`SEALD: [Z None
`CSS: X None
`Product Quality g None
`Other: IX None
`
`
`
`
`
`{0 Medication Guide/Patient Package Insert/Instructions for Use/Device Labeling (write
`submission/communication date at upper right offirstpage ofeachpiece)
`____________________________________________________________________________________________________________________________________________________________________________________________________
`0 Most-recent draft labeling (ifit is division—proposed labeling, it should be in
`track-changesformat)
`0 Original applicant—proposed labeling
`
`'3' Labels (full color carton and immediate-container labels) (write
`submission/communication date on upper right offirstpage ofeach submission)
`
`0 Most-recent draft labeling
`
`03° Proprietary Name
`Acceptability/non-acceptability letter(s) (indicate date(s))
`Review(s) (indicate date(s)
`
`0
`
`v Labehng renews (indicate dates ofreviews)
`
`'3' RPM Filing Review/Mono ofFiling Meeting (indicate date ofeach review)
`$0 All NDA 505(b)(2) Actions: Date each action cleared by 505(b)(2) Clearance Committee
`
`Deco-bet 23’ 2016
`IX Not a (b)(2)
`
`6° NDAs only: Exclusivity Summary (signed by Division Director)
`
`IX Included
`
`'3' Application Integrity Policy (AIP) Status and Related Documents
`hflpflwww fda.gov/1CECI/EnforcementActions/ApplicationIntegg'gPolicy/default htm
`
`4 Filing reviews for scientific disciplines are NOT required to be included in the action package.
`
`Reference ID: 3951969
`
`

`

`
`
`
`
`O Mid-cycle Communication (indicate date ofmtg)
`
`
`I: N/A February 11. 2016
`
`0
`
`Late-cycle Meeting (indicate date ofmtg)
`
`I:] N/A April 19. 2016
`
`0 Other milestone meetings (e.g.. EOP2a. CMC focused milestone meetings)
`(indicate dates 0 mt_ s)
`
`N/A
`
`°§° Advisory Committee Meeting(s)
`
`0 Date(s) of Meeting(s)
`
`IX] No AC meeting
`
`0
`
`This application is on the AIP
`0
`Ifyes. Center Director’s Exception for Review memo (indicate date)
`
`El Yes D No
`
`0
`
`Ifyes. 0C clearance for approval (indicate date ofclearance
`.
`.
`a
`comnmmcatton)
`
`D NotanAP action
`
`'3' Pediatrics (approvals only)
`0 Date reviewed by PeRC May 11. 2016
`If PeRC review not necessary. explain:
`
`‘2' Breakthrough Therapy Designation
`
`E] N/A
`
`Granted May 15. 2015
`Rescinded April 1. 2015
`Intent to Rescind: February 4,
`2015
`Granted: Aril 22. 2014
`
`0
`
`0
`
`0
`
`Breakthrough Therapy Designation Letter-(s) (granted. denied. an/or rescinded)
`
`CDER Medical Policy Council Breakthrough Therapy Designation
`Determination Review Template(s) (include only the completed template(s) and
`not the meetin minutes)
`
`N/A
`
`CDER Medical Policy Council Brief — Evaluating a Breakthrough Therapy
`Designation for Rescission Template(s) (include only the completed template(s)
`and not the meeting minutes)
`
`May 14. 2014
`
`(completed CDER IMPC templates can befound in DARRTS as clinical reviews or on
`the MPC SharePoint Site
`
`°1° Outgoing communications: letters. emails. and faxes considered important to include in
`the action package by the reviewing oifice/division (e.g.. clinical SPA letters. RTF letter.
`Formal Dispute Resolution Request decisional letters. etc.) (do not include previous
`action letters, as these are located elsewhere in acka_ e)
`Internal documents: memoranda. telecons. emails. and other documents considered
`
`02°
`
`Included
`
`important to include in the action package by the reviewing ofiice/division (e.g..
`Re to Briefin- minutes. Medical Poli Council meetin minutes
`
`N/A
`
`°1° Minutes of Meetings
`
`El None
`June 28. 2016
`‘3’ Oflice Director Decisional Memo (indicate datefor each review)
`|:]NoneJunel62016
`""""""""DvisonDirectorSummaryReew(znd1catedatefozeaclevIeI)
`""""""""ELQQBAQLQEL'EQQIQIQQEQ1Q;}§ZQ}§§;};};};}Q}LZL§M.) EINonJun12016
`"""""""EEQEBELQLQQEQL};'EZEQLQZEL}nb) I:]NonJun242016
`
`Reference ID: 3951969
`
`
`
`

`

`NDAIBLA #
`
`Page 5
`
`'3' Clinical Reviews
`
`0
`
`0
`
`0
`
`Clinical Team Leader Review(s) (indicate datefir each review)
`
`Clinical review(s) (indicate datefor each review)
`
`IX No separate review
`
`June 1_. 2016 (Addendum)
`March 29, 2016
`
`Social scientist review(s) (if OTC drug) (indicate datefor each review)
`
`IX None
`
`4° Financial Disclosure reviews(s) or location/date if addressed in another review
`OR
`Ifno financial disclosure information was required, check here El and include a
`review/memo explaining why not (indicate date ofreview/memo)
`
`March 29, 2016
`Page 160
`
`.
`°:° Clinical reviews from immunology and other clinical areas/divisions/Centers (indicate
`date ofeach review)
`
`one
`‘2 N
`
`03° Controlled Substance Stafl'review(s) and Scheduling Recommendation (indicate date of
`each review)
`
`[Z NlA
`
`{0 Risk Management
`0
`REMS Documents and REMS Supporting Document (indicate date(s) of
`submission(s))
`REMS Memo(s) and letter(s) (indicate date(s))
`Risk manage-ent review(s) and recommendations (including those by OSE and
`CSS) (indicate date ofeach review and indicate location/date flincorporated
`into another review
`
`El None April 19,. 2016
`
`°.° DSI Chmcal Inspection Revrew Summary(1es) (Include copies of051 letters to
`tm'estlgatm s)
`
`D None re
`
`I
`
`ted May 13’ 2016
`
`4° Clinical Microbiology Team Leader Review(s) (indicate datefor each review)
`""""""
`""""""""
`""""""""""""":"""""""j
`Clinical Microbiology Rev1ew(s) (Indicate datefor each Ieweu)
`
`IX No separate review
`DNoneMarch E53613"""""""""
`March 24’ 2016
`
`'3' Statistical Division Director Review(s) (indicate datefor each review)
`
`Statistical Team Leader Review(s) (indicate datefor each review)
`
`Statistical Review(s) (indicate datefor each review)
`
`IX No separate review
`
`IX No separate review
`
`I: None March 29, 2016
`
`'3' Clinical Pharmacology Division Director Review(s) (indicate datefor each revieu)
`
`IX No separate review
`
`
`
`
`
`Clinical Pharmacology Team Leader Review(s) (indicate datefor each review)
`
`Clinical Pharmacology review(s) (indicate datefor each review)
`
`X No separate review
`"mlj"fi3fi€""}iifié‘i‘f§6'i‘6 """""""""""
`(Addendum)
`March 25, 2016
`
`'2' 081 Clinical Pharmacology Inspection Review Summary (include copies of 081 letters)
`
`[2 None requested
`
`Reference ID: 3951969
`
`

`

`NDAIBLA #
`
`Page 6
`
`'2' Pharmacology/1'oxicology Discipline Reviews
`
`0
`
`0
`
`Supervisory Review(s) (indicate datefor each review)
`
`Pharm/tox review(s), including referenced IND revrews (indicate datefor each
`renew)
`
`E] No separate review March 24,
`201 6
`
`E No separate review
`
`C] None March 28. 2016
`
`0? Review(s) by other disciplines/divisions/Centers requested by P/T reviewer (indicate date
`_
`for each reweu)
`
`IX None
`
`°3° Statistical review(s) of carcinogenicity studies (indicate datefor each review)
`
`IX No carc
`
`-
`.
`. ECAC/CAC report/memo of meeting
`
`'2' 081 Nonclinical Inspection Review Summary (include copies of081 letters)
`
`4° Product Quality Discipline Reviews
`
`IX] None
`Included in PIT review. a . e
`
`IE None requested
`
`
`
`
`
`
`
`
`
`0
`
`0
`
`0
`
`Tertiary review (indicate datefor each review)
`
`IX None
`
`Secondary review (e.g., Branch Chief) (indicate datefor each review)
`
`IX None
`
`Integrated Quahty Assessment (contains the Erecutive. Summary and the primary D None
`rev1ews from each product quality renew d1sc1plme) (mdlcate datefor each
`review)
`
`June 24’ 2016
`April 1 2016
`’
`
`'3' Reviews by other disciplines/divisions/Centers requested by product quality review team
`.
`.
`.
`(Indicate date ofeach review)
`
`IX None
`
`‘3' Environmental Assessment (check one) (original and supplemental applications)
`
`IX Categorical Exclusion (indicate review date)(all original applications and
`all eflicaqv supplements that could increase the patientpopulation)
`
`April 1, 2016
`Page 140 Product Quafity IQA
`
`[I Review & FONSI (indicate date of review)
`
`El Review & Environmental Impact Statement (indicate date ofeach review)
`
`°:° Facilities Review/Inspection
`
`g Facilities inspections (action must be taken prior to the re—evaluation date) (onlv
`_
`_
`_
`_
`_
`_
`'
`original applications and efi'icacy supplements that require a manufacturing
`fafihi’n‘ Inspection(e.g., new strength, manufacturingprocess, or manufacturing
`S’ e c ange)
`
`IE Acceptable
`Re-evaluation date'
`El Withhold rec
`I: Not applicable
`
`endation
`
`Reference ID: 3951969
`
`

`

`NDA/BLA #
`Page 7
`
`Day of Approval Activities
`
` For all 505(b)(2) applications:
` Check Orange Book for newly listed patents and/or exclusivity (including
`pediatric exclusivity)
`
`Finalize 505(b)(2) assessment
`
` For Breakthrough Therapy (BT) Designated drugs:
` Notify the CDER BT Program Manager
` For products that need to be added to the flush list (generally opioids): Flush List
` Notify the Division of Online Communications, Office of Communications
` Send a courtesy copy of approval letter and all attachments to applicant by fax or secure
`email
` If an FDA communication will issue, notify Press Office of approval action after
`confirming that applicant received courtesy copy of approval letter
` 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
`identified as the “preferred” name
` Ensure Pediatric Record is accurate
`
` Send approval email within one business day to CDER-APPROVALS
`
` No changes
` New patent/exclusivity (Notify
`CDER OND IO)
`
` Done
`
` Done
`(Send email to CDER OND IO)
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
` Done
`
`Reference ID: 3951969
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`06/28/2016
`
`Reference ID: 3951969
`
`

`

`
`
`
`
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`Public Health Service
`
`Division of Antiviral Drug Products
`Food and Drug Administration
`Silver Spring, MD 20903
`MEMORANDUM OF ELECTRONIC MAIL CORRESPONDENCE
`
`208341
`NDA:
`
`sofosbuvir/velpatisvir FDC
`Drug:
`
`June 17, 2016
`Date:
`
`Prachi Shah MBS, RAC, Manager, Regulatory Affairs
`To:
`
`
`Gilead Sciences, Inc.
`Sponsor:
`
`
`
`
`
`
`NDA 208341 DAVP Proposed Labeling Changes
`Subject:
`______________________________________________________________________________
`Please find attached the Division’s labeling edits for NDA 208341. A word copy of the label
`will be attached to this correspondence.
`
`Please provide your response/revised labeling by June 21, 2016.
`
`We are providing this above information via e-mail for your convenience. Please feel free to
`contact me at 301-796-0759 if you have any questions regarding the contents of this
`transmission.
`
`
`
`
`
`
`_____________________________
`Linda Onaga, MPH
`Senior Regulatory Project Manager
`Division of Antiviral Products
`Office of Antimicrobial Products
`Center for Drug Evaluation and Research
`
`_________________________________________________________________________________________________
`DAVP/HFD-530 • 10903 New Hampshire Ave • Silver Spring, MD 20903 • (301) 796-1500 • Fax: (301) 796-9883
`
`Reference ID: 3947829
`
`35 Page(s) of Draft Labeling have been Withheld in Full as b4 (CCI/TS) immediately following this page
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`LINDA C ONAGA
`06/17/2016
`
`Reference ID: 3947829
`
`

`

`PeRC Meeting Minutes
`May 11, 2016
`
`
`
`PeRC Members Attending:
`Lynne Yao
`Meshaun Payne
`Dianne Murphy
`Gerri Baer
`Peter Starke
`Gil Burckart
`Raquel Tapia
`Greg Reaman
`Dionna Green
`Robert “Skip” Nelson
`Kevin Krudys
`Barbara Buch
`Rosemary Addy
`Shrikant Pagay
`Adrienne Hornatko-Munoz
`Wiley Chambers
`Jackie Yancy
`Thomas Smith
`John Alexander
`Karen Davis-Bruno
`
`
`
`
`
`
`
`Reference ID: 3943338
`
`
`Page 1 of 12
`
`1 Page(s) has been Withheld in Full as Non Responsive immediately
`following this page
`
`

`

`NDA
`208341
`
`Sofosbuvir/Velpatasvir (Partial
`Waiver/Deferral/Plan) with Agreed
`iPSP
`
`11:30
`
`DAVP
`
`Linda Onaga
`
`Treatment of chronic hepatitis C
`infection in adults
`
`
`
`
`
`
`
`Reference ID: 3943338
`
`
`Page 3 of 12
`
`Non Responsive
`
`Non Responsive
`
`Non Responsive
`
`6 Page(s) have been Withheld in Full as Non Responsive
`immediately following this page
`
`

`

`Sofosbuvir/Velpatasvir (Partial Waiver/Deferral/Plan) with Agreed iPSP
`• Proposed Indication: Treatment of chronic hepatitis C infection in adults
`• This product triggers PREA as a new indication.
`• The division noted that there is agreed iPSP and the division agrees with the plan as
`outlined in the agreed iPSP. The plan includes waiver for patients < 3 years of age
`(because of the potential for spontaneous resolution of HCV); and deferral for patients 3
`to < 18 years of age. This product has high promise in the treatment of HCV in children
`because it appears to be effective in all major HCV genotypes and is a regimen that does
`not require interferon or ribavirin.
`• The division stated the Written Request for this product is completed but has not been
`issued.
`• PeRC Recommendations:
`o The PeRC agreed with the spon