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`DEPARTMENT OF HEALTH AND HUMAN SERVICES
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`NDA 208745/S-002
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`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
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`Synergy Pharmaceuticals, Inc.
`Attn: Evelyn Jaeger
`Vice President Regulatory Affairs & Clinical Quality Assurance
`420 Lexington Avenue
`Suite 2012
`New York, NY 10170
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`Dear Ms. Jaeger:
`
`Please refer to your Supplemental New Drug Application (sNDA), received February 7, 2018,
`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for
`Trulance™ (plecanatide) 3mg oral tablet.
`
`This “Changes Being Effected” supplemental new drug application proposes to modify the
`approved label for clarity and consistency as follows:
`
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`• Table 4 - Study 3, in the Treatment Difference column an end parenthesis was changed to
`an end bracket for consistency.
`In Table 4, for Study 3 change to the placebo N to 350 and change to the TRULANCE N
`to 349. This response was not incorporated in the approved labeling by Synergy;
`however, these numbers are consistent with the descriptive text in Section 14.2.
`In Table 4, for Study 4, change to the TRULANCE N to 375. This response was not
`incorporated in the approved labeling by Synergy; however, these numbers are consistent
`with the descriptive text in Section 14.2.
`In addition, during the verification of the Table 4 N (s), Synergy found one additional
`data change to the Study 3 Treatment Difference column: [95% CIa] which should read
`[6%, 18%] rather than [6%,19%].
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`•
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`•
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`•
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application, as amended. It is approved,
`effective on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling
`text.
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`We note that your February 7, 2018, submission includes final printed labeling (FPL) for your
`package insert and Medication Guide. We have not reviewed this FPL. You are responsible for
`assuring that the wording in this printed labeling is identical to that of the approved content of
`labeling in the structured product labeling (SPL) format.
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`Reference ID: 4296564
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`

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`NDA 208745/S-002
`Page 2
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`CONTENT OF LABELING
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`As soon as possible, but no later than 14 days from the date of this letter, submit the content of
`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
`automated drug registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
`of labeling must be identical to the enclosed labeling (text for the package insertand Medication
`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
`supplements, as well as annual reportable changes not included in the enclosed labeling.
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`Information on submitting SPL files using eList may be found in the guidance for industry titled
`“SPL Standard for Content of Labeling Technical Qs and As” at
`http://www.fda.gov/downloads/DrugsGuidanceComplianceRegulatoryInformation/Guidances/U
`CM072392.pdf.
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`The SPL will be accessible from publicly available labeling repositories.
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`Also within 14 days, amend all pending supplemental applications that include labeling changes
`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
`changes approved in this supplemental application, as well as annual reportable changes and
`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
`should provide appropriate annotations, including supplement number(s) and annual report
`date(s).
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit the following, in triplicate, (1) a cover letter requesting advisory
`comments, (2) the proposed materials in draft or mock-up form with annotated references, and
`(3) the package insert(s) to:
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`OPDP Regulatory Project Manager
`Food and Drug Administration
`Center for Drug Evaluation and Research
`Office of Prescription Drug Promotion (OPDP)
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD format.
`For more information about submitting promotional materials in eCTD format, see the draft
`Guidance for Industry (available at:
`http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U
`CM443702.pdf ).
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`Reference ID: 4296564
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`

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`NDA 208745/S-002
`Page 3
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`You must submit final promotional materials and package insert(s), accompanied by a Form
`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
`FDA 2253 is available at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf.
`Information and Instructions for completing the form can be found at
`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
`more information about submission of promotional materials to the Office of Prescription Drug
`Promotion (OPDP), see http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm.
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA
`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Evangela Covert, Regulatory Project Manager, at (301) 796-4075.
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`Sincerely,
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`{See appended electronic signature page}
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`Joyce Korvick, M.P.H., M.D.
`Deputy Director, Safety
`Division of Gastroenterology and Inborn Errors
`Products
`Office of Drug Evaluation III
`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
`Content of Labeling
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`
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`Reference ID: 4296564
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`

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`Signature Page 1 of 1
`--------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically. Following this are manifestations of any and all
`electronic signatures for this electronic record.
`--------------------------------------------------------------------------------------------
`/s/
`------------------------------------------------------------
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`JOYCE A KORVICK
`07/25/2018
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`Reference ID: 4296564
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