`
`
`
`DEPARTMENT OF HEALTH AND HUMAN SERVICES
`
`
`
`
`
`
`NDA 207620/S-008
`
`
`
`
`
`
`Food and Drug Administration
`Silver Spring MD 20993
`
`SUPPLEMENT APPROVAL
`
`
`
`Novartis Pharmaceuticals Corporation
`Attention: Amol Parekh, PharmD
`Global Program Regulatory Manager, Drug Regulatory Affairs
`One Health Plaza, Building 100
`East Hanover, NJ 07936
`
`Dear Dr. Parekh:
`
`Please refer to your Supplemental New Drug Application (sNDA) dated and received July 27, 2017, and
`your amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
`for Entresto (sacubitril/valsartan) 24/26 mg; 49/51 mg; 97/103 mg Tablets.
`
`This supplemental new drug application provides for revisions to the approved labeling as follows
`(additions are shown as underlined text and deletions are shown as strikethrough text):
`
`
`1. Under WARNINGS AND PRECAUTIONS/Angioedema, the following text was added to the
`last paragraph:
`
`
`
`
`
`
`
`
`
`
`Patients with a prior history of angioedema may be at increased risk of angioedema with
`ENTRESTO [see Adverse Reactions (6.1)]. ENTRESTO should must not be used in
`patients with a known history of angioedema related to previous ACE inhibitor or ARB
`therapy [see Contraindications (4)]. ENTRESTO should not be used in patients with
`hereditary angioedema.
`
`2. Under ADVERSE REACTIONS, the following section was added:
`
`
`Postmarketing Experience
`6.2
`The following additional adverse reactions have been reported in postmarketing
`experience. Because these reactions are reported voluntarily from a population of
`uncertain size, it is not always possible to reliably estimate their frequency or establish a
`causal relationship to drug exposure.
`Hypersensitivity, including rash, pruritus and anaphylactic reaction
`
`3. Under What should I tell my doctor before taking ENTRESTO? the following bullet was
`added:
`
`• have a history of hereditary angioedema
`
`
`The following revision was made to the Entresto Patient Package Inset:
`
`
`Reference ID: 4185290
`
`

`

`NDA 207620/S-008
`Page 2
`
`
`
`4. The CONTENTS section was updated to reflect the addition of the new section (6.2).
`
`
`
`
`5. The revision date and version numbers were updated.
`
`
`There are no other changes from the last approved package insert.
`
`APPROVAL & LABELING
`
`We have completed our review of this supplemental application, as amended, and it is approved, effective
`on the date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
`
`CONTENT OF LABELING
`
`As soon as possible, but no later than 14 days from the date of this letter, submit the content of labeling
`[21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA automated drug
`registration and listing system (eLIST), as described at
`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content of
`labeling must be identical to the enclosed labeling (text for the package insert, text for the patient package
`insert), 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.
`
`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/UCM0723
`92.pdf.
`
`The SPL will be accessible from publicly available labeling repositories.
`
`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).
`
`PROMOTIONAL MATERIALS
`
`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:
`
`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
`
`
`Reference ID: 4185290
`
`

`

`NDA 207620/S-008
`Page 3
`
`
`
`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/UCM4437
`02.pdf ).
`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.
`
`All promotional materials that include representations about your drug product must be promptly revised
`to be consistent with the labeling changes approved in this supplement, including any new safety
`information [21 CFR 314.70(a)(4)]. The revisions in your promotional materials should include
`prominent disclosure of the important new safety information that appears in the revised package
`labeling. Within 7 days of receipt of this letter, submit your statement of intent to comply with
`21 CFR 314.70(a)(4) to the address above, by fax to 301-847-8444, or 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/UCM4437
`02.pdf ).
`
`REPORTING REQUIREMENTS
`
`We remind you that you must comply with reporting requirements for an approved NDA (21 CFR 314.80
`and 314.81).
`If you have any questions, please call:
`
`Lori Anne Wachter, RN, BSN, RAC
`Regulatory Project Manager for Safety
`(301) 796-3975
`
`
`Sincerely,
`
`{See appended electronic signature page}
`
`Mary Ross Southworth, PharmD.
`Deputy Director for Safety
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
`
`
`ENCLOSURE(S):
`Content of Labeling
`
`Reference ID: 4185290
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`MARY R SOUTHWORTH
`11/22/2017
`
`Reference ID: 4185290
`
`(
`
`
`
`