`NDA 218591
`
`NDA 207620/S-025
`
`
`Novartis Pharmaceuticals Corporation
`
`Attention: Byron Griffith, PhD
`
`Senior Global Program Regulatory Manager
`One Health Plaza
`Building 337
`
`East Hanover, New Jersey 07936-1080
`
`
`Dear Dr. Griffith:
`
`
`
` NDA APPROVAL
`
`
`
`Please refer to your new drug application (NDA) and your supplemental new drug
`
`
`
`
`application (sNDA) dated June 14, 2023, received, June 14, 2023 and your
`
`
`
`amendments, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
`
`
`
`Act (FDCA) for:
`
`
`• Entresto Sprinkle (sacubitril/valsartan) oral pellets
`• Entresto (sacubitril/valsartan) tablets
`
`
`
`
`
`
`
`This NDA and sNDA provide for the use of Entresto (sacubitril/valsartan) tablets and
`
`
`
`oral pellets for:
`
`• The treatment of symptomatic heart failure with systemic left ventricular systolic
`dysfunction in pediatric patients aged one year and older. ENTRESTO reduces
`NT-proBNP and is expected to improve cardiovascular outcomes.
`
`
`APPROVAL & LABELING
`
`
`
`We have completed our review of these applications, as amended. They are approved,
`
`
`effective on the date of this letter, for use as recommended in the enclosed agreed-
`
`upon labeling.
`
`
`
`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
`
`
`FDA.gov.1 Content of labeling must be identical to the enclosed labeling (text for the
`
`
`
`Prescribing Information, Patient Package Insert, and Instructions for Use) as well as
`
`
`
` 1 http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm
`
`
`
`Reference ID: 5363847
`
`

`

`
`
` NDA 218591
`
` sNDA 207620/S-025
`
`Page 2
`
`
`annual reportable changes not included in the enclosed labeling. Information on
`submitting SPL files using eLIST may be found in the guidance for industry SPL
`
`
`
`Standard for Content of Labeling Technical Qs and As.2
`
`
`
`
`The SPL will be accessible via publicly available labeling repositories.
`
`
`CARTON AND CONTAINER LABELING
`
`
`Submit final printed carton and container labeling that are identical to the enclosed
`
`carton and container labeling, as soon as they are available, but no more than 30 days
`
`after they are printed. Please submit these labeling electronically according to the
`
`
`guidance for industry SPL Standard for Content of Labeling Technical Qs & As. For
`administrative purposes, designate this submission “Final Printed Carton and
`
`Container Labeling for approved NDA 218591.” Approval of this submission by FDA
`
`
`is not required before the labeling is used.
`
`
`DATING PERIOD
`
`
`Based on the stability data submitted to date, the expiry dating period for Entresto
`
`
`Sprinkle (sacubitril/valsartan) oral pellets shall be 36 months from the date of
`
`
`
`
`manufacture when stored at 20°C to 25°C .
`
`ADVISORY COMMITTEE
`
`
`Your applications for Entresto Sprinkle and Entresto were not referred to an FDA
`
`
`
`advisory committee because, the application did not raise significant public health
`questions on the role of the drug in the diagnosis, cure, mitigation, treatment, or
`
`
`
`prevention of a disease
`
`
`PROMOTIONAL MATERIALS
`
`
`You may request advisory comments on proposed introductory advertising and
`promotional labeling. For information about submitting promotional materials, see the
`final guidance for industry Providing Regulatory Submissions in Electronic and Non-
`
`Electronic Format—Promotional Labeling and Advertising Materials for Human
`
`Prescription Drugs.3
`
`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials,
`
`and the Prescribing Information, at the time of initial dissemination or publication,
`
`
`
`
`2 We update guidances periodically. For the most recent version of a guidance, check the FDA Guidance
`
`
`
`
`
`
`
`
`
`
`Documents Database https://www.fda.gov/RegulatoryInformation/Guidances/default.htm.
`
`
`
`3 For the most recent version of a guidance, check the FDA guidance web page at
`
`
`
`
`
`
`
`
`
`
`https://www.fda.gov/media/128163/download.
`
`
`U.S. Food and Drug Administration
`
`
`
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 5363847
`
`

`

`
`
`
`
`
`
` NDA 218591
`
` sNDA 207620/S-025
`
`Page 3
`
`
`accompanied by a Form FDA 2253. Form FDA 2253 is available at FDA.gov.4
`
`
`
`
`Information and Instructions for completing the form can be found at FDA.gov.5
`
`PATENT LISTING REQUIREMENTS
`
`
`
`
`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
`submitted in a supplement require you to submit patent information for listing in the
`
`Orange Book upon approval of the supplement. You must submit the patent information
`
`
`required by 21 CFR 314.53(d)(2)(i)(A) through (C) and 314.53(d)(2)(ii)(A) and (C), as
`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
`
` supplement for the patent information to be timely filed (see 21 CFR
` 314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
`
`
`
`
` require the submission of a request to remove patent information from the Orange Book
`
`
` are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
`
` 314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
`
`METHODS VALIDATION
`
`
` We have not completed validation of the regulatory methods. However, we expect your
`
` continued cooperation to resolve any problems that may be identified.
`
` REPORTING REQUIREMENTS
`
` We remind you that you must comply with reporting requirements for an approved NDA
`
`
` (21 CFR 314.80 and 314.81).
`
` COMPENDIAL STANDARDS
`
` A drug with a name recognized in the official United States Pharmacopeia or official
`
`
`
` National Formulary (USP-NF) generally must comply with the compendial standards for
`
` strength, quality, and purity, unless the difference in strength, quality, or purity is plainly
`stated on its label (see FD&C Act § 501(b), 21 USC 351(b)). FDA typically cannot share
`application-specific information contained in submitted regulatory filings with third
`parties, which includes USP-NF. To help ensure that a drug continues to comply with
`compendial standards, application holders may work directly with USP-NF to revise
`
`official USP monographs. More information on the USP-NF is available on USP’s
`
`website6.
`
`
`
`
`
`
`
`
`
`4 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM083570.pdf
`
`
`5 http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf
`
`
`6 https://www.uspnf.com/
`
`
`
`U.S. Food and Drug Administration
`
`
`
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 5363847
`
`

`

`
`
`
`
`
`
` NDA 218591
`
` sNDA 207620/S-025
`
`Page 4
`
`
`REQUIRED PEDIATRIC ASSESSMENTS
`
`
` Under the Pediatric Research Equity Act (PREA) (21 U.S.C. 355c), all applications for
`
`
`
` new active ingredients (which includes new salts and new fixed combinations), new
` indications, new dosage forms, new dosing regimens, or new routes of administration
`
`
` are required to contain an assessment of the safety and effectiveness of the product for
` the claimed indication in pediatric patients unless this requirement is waived, deferred,
`
`
` or inapplicable.
`
`
`
`We are waiving the pediatric study requirement for this application because pediatric
`
`
`patients birth to less than 1 month of age because studies are impossible or highly
`
`
`
`impractical because the number of patients with heart failure and left ventricular systolic
`
`
`disfunction would be too small.
`
`
`
`
`We note that you have fulfilled the pediatric study requirements for ages 1 month to
`
`
`less than 18 years of age for this application.
`
`
`
`
`If you have any questions, please contact Maryam Changi, Regulatory Project Manager,
`
`
`
`
`at maryam.changi@fda.hhs.gov.
`
`
`
`
`Sincerely,
`
`
`
`{See appended electronic signature page}
`
`Norman Stockbridge, MD, PhD
`
`Director
`
`Division of Cardiology and Nephrology
`
`
`
`Office of Cardiology, Hematology,
`
`
`Endocrinology, and Nephrology
`
`Office of New Drugs
`
`Center for Drug Evaluation and Research
`
`
`
`
`
`
`
`
`ENCLOSURE(S):
`
`• Content of Labeling
`
`
`
`o Prescribing Information
`
`
`o Patient Package Insert
`
`
`Instructions for Use
`
`
`o
`• Carton and Container Labeling
`
`
`
`
`U.S. Food and Drug Administration
`
`
`
`
`
`Silver Spring, MD 20993
`
`www.fda.gov
`
`Reference ID: 5363847
`
`

`

`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
`04/12/2024 03:42:28 PM
`
`Reference ID: 5363847
`
`