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` NDA 207620/S-013
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`SUPPLEMENT APPROVAL
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` Novartis Pharmaceuticals Corp.
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` Attention: Amol Parekh, PharmD
` Sr. Global Program Regulatory Manager
`
`One Health Plaza
` Building 315, Room 5250A
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` East Hanover, NJ 07936
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`Dear Dr. Parekh:
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`Please refer to your supplemental new drug application (sNDA) dated April 1, 2019,
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`received April 1, 2019, and your amendments, submitted under section 505(b) of the
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`Federal Food, Drug, and Cosmetic Act (FDCA) for Entresto® (sacubitril/valsartan),
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`Tablets.
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`This Prior Approval supplemental new drug application, submitted in response to a
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`Pediatric Written Request, supports a labeled indication for use of Entresto® for
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`treatment of symptomatic heart failure with systemic left ventricular systolic dysfunction
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`in pediatric patients aged one year and older. Entresto® reduces NT-proBNP and is
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`expected to improve cardiovascular outcomes.
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`APPROVAL & LABELING
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`We have completed our review of this application. It is approved, effective on the date of
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`this letter, for use as recommended in the enclosed agreed-upon labeling.
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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
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`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using
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`the FDA automated drug registration and listing system (eLIST), as described at
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`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
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`Prescribing Information, Patient Package Insert), with the addition of any labeling
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`changes in pending “Changes Being Effected” (CBE) supplements, as well as annual
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`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
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`industry SPL Standard for Content of Labeling Technical Qs and As.2
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` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
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` 2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
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` Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`Reference ID: 4499982
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`

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` NDA 207620/S-013
` Page 2
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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
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`changes for this NDA, including CBE supplements for which FDA has not yet issued an
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`action letter, with the content of labeling [21 CFR 314.50(l)(1)(i)] in Microsoft Word
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`format, that includes the changes approved in this supplemental application, as well as
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`annual reportable changes. To facilitate review of your submission(s), provide a
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`highlighted or marked-up copy that shows all changes, as well as a clean Microsoft
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`Word version. The marked-up copy should provide appropriate annotations, including
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`supplement number(s) and annual report date(s).
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`REQUIRED PEDIATRIC ASSESSMENTS
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`Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
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`new active ingredients (which includes new salts and new fixed combinations), new
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`indications, new dosage forms, new dosing regimens, or new routes of administration
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`are required to contain an assessment of the safety and effectiveness of the product for
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`the claimed indication in pediatric patients unless this requirement is waived, deferred,
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`or inapplicable.
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`PREA assessments were previously waived under the original NDA submission. This
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`Prior Approval Supplement triggered PREA for a new dosage regimen. This submission
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`contained pediatric data that fulfilled a pediatric assessment in children ages 1 year to
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`<18 years with dilated cardiomyopathy (DCM). We are waiving the pediatric study
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`requirement for ages one month to <1 year because necessary studies are impossible
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`or highly impracticable because of rarity of DCM in this age group.
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`We are waiving the pediatric study requirement for ages 0 to one month because there
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`is evidence strongly suggesting that the drug product would be ineffective and unsafe in
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`this pediatric group because of potential impact of renin-angiotensin system blockade
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`on kidney development.
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4499982
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` NDA 207620/S-013
` Page 3
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` PROMOTIONAL MATERIALS
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` You may request advisory comments on proposed introductory advertising and
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` 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
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` annotated references, and (3) the Prescribing Information to:
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`OPDP Regulatory Project Manager
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`Food and Drug Administration
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`Center for Drug Evaluation and Research
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`Office of Prescription Drug Promotion (OPDP)
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`5901-B Ammendale Road
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`Beltsville, MD 20705-1266
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`Alternatively, you may submit a request for advisory comments electronically in eCTD
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`format. For more information about submitting promotional materials in eCTD format,
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`see the draft guidance for industry Providing Regulatory Submissions in Electronic and
`Non-Electronic Format-Promotional Labeling and Advertising Materials for Human
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`Prescription Drugs.3
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`You must submit final promotional materials and Prescribing Information, accompanied
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`by a Form FDA 2253, at the time of initial dissemination or publication
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`[21 CFR 314.81(b)(3)(i)]. Form FDA 2253 is available at FDA.gov.4 Information and
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`Instructions for completing the form can be found at FDA.gov.5 For more information
`about submission of promotional materials to the Office of Prescription Drug Promotion
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`(OPDP), see FDA.gov.6
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`REPORTING REQUIREMENTS
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` We remind you that you must comply with reporting requirements for an approved NDA
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` (21 CFR 314.80 and 314.81).
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` 3 When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent
` version of a guidance, check the FDA guidance web page at
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` https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
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`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
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` 5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
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` 6 http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm090142.htm
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4499982
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`

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`Sincerely,
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`{See appended electronic signature page}
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`
`Norman Stockbridge, M.D., Ph.D.
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`Director
`
`Division of Cardiovascular and Renal Products
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`Office of Drug Evaluation I
`
`Center for Drug Evaluation and Research
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`NDA 207620/S-013
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`Page 4
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`If you have any questions, please call Alexis Childers, Sr. Regulatory Project Manager
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`at (301) 796-0442.
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`ENCLOSURE(S):
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`• Content of Labeling
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`o Prescribing Information
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`o Patient Package Insert
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`U.S. Food and Drug Administration
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`Silver Spring, MD 20993
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`www.fda.gov
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`Reference ID: 4499982
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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/
`------------------------------------------------------------
`
`NORMAN L STOCKBRIDGE
`10/01/2019 03:44:01 PM
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`Reference ID: 4499982
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`(
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