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` NDA 208700/S-019
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`NDA 208700/S-023
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` SUPPLEMENT APPROVAL/
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` FULFILLMENT OF POSTMARKETING COMMITMENT
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`Advanced Accelerator Applications USA, Inc.
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`Attention: Jouliana Jean Paul, J.D.
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`Global Program Regulatory Director
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`57 E. Willow Street
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`Millburn, NJ 07041
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`Dear Ms. Paul:
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`Please refer to your supplemental new drug application (sNDA) dated and received
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`August 13, 2021, and February 25, 2022, respectively, and your amendments,
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`submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA)
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`for Lutathera (lutetium Lu 177 dotatate) injection.
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`NDA 208700/019:
`This Prior Approval sNDA provides for revisions to the CLINICAL STUDIES,
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`Progressive, Well-differentiated Advanced or Metastatic Somatostatin Receptor-Positive
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`Midgut Carcinoid Tumors (14.1) subsection of the package insert (PI) based on the
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`results of the final overall survival analysis of the NETTER-1 trial. Subsection 5.3
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`(Secondary Myleodysplastic Syndrome and Leukemia) of the WARNINGS AND
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`PRECAUTIONS section was also updated based on the additional follow-up information
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`provided. Minor changes were also made to other sections of labeling to enhance
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`clarity and brevity.
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`NDA 208700/023:
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`This Prior Approval sNDA provides for the addition of Hypersensitivity Reactions (5.6) in
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`the WARNINGS AND PRECAUTIONS section, along with corresponding updates to the
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`DOSAGE AND ADMINISTRATION, Important Safety Instructions (2.1), Premedication
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`and Concomitant Medications (2.3), Dosage Modifications for Adverse Reactions (2.4);
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`ADVERSE REACTIONS (6) and Postmarketing Experience (6.2); and, PATIENT
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`COUNSELING INFORMATION (17) sections of the PI.
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`APPROVAL & LABELING
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`We have completed our review of this application, as amended. It is approved, effective
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`on the date of this letter, for use as recommended in the enclosed agreed-upon
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`labeling.
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`Reference ID: 4998594
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`

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` NDA 208700/S-019 and S-023
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` Page 2
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`WAIVER OF ½ PAGE LENGTH REQUIREMENT FOR HIGHLIGHTS
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` Please note that we have previously granted a waiver of the requirements of 21 CFR
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` 201.57(d)(8) regarding the length of Highlights of Prescribing Information.
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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
` 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), with the addition of any labeling changes in pending “Changes
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`Being Effected” (CBE) supplements, as well as annual reportable changes not included
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`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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`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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`Because none of these criteria apply to your applications, you are exempt from this
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`requirement.
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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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`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: 4998594
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` NDA 208700/S-019 and S-023
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` Page 3
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`FULFILLMENT OF POSTMARKETING COMMITMENT
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` We have received your submission dated August 13, 2021, under NDA 208700/019,
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` containing the final report for the following postmarketing commitment listed in the
` January 26, 2018, approval letter.
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`3326-03 Submit the final clinical report and datasets at the time of the final analysis
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`for overall survival (OS) for Trial NETTER-1, entitled “A Multicentre,
`stratified, open, randomized, comparator-controlled, parallel-group phase
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` III study comparing treatment with 177 Lu-DOTA0-Tyr3-Octreotate to
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`Octreotide LAR in Patients with Inoperable, Progressive, Somatostin
`Receptor Positive, Midgut Carcinoid Tumors”, to revise product labeling
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`with mature OS data.
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`We have reviewed your submission and conclude that the above commitment was
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`fulfilled.
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`We remind you that there are postmarketing requirements listed in the
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`January 26, 2018, approval letter that are still open.
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`PROMOTIONAL MATERIALS
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`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-
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`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
`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
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`PATENT LISTING REQUIREMENTS
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`Pursuant to 21 CFR 314.53(d)(2) and 314.70(f), certain changes to an approved NDA
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`submitted in a supplement require you to submit patent information for listing in the
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` 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
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`applicable, to FDA on Form FDA 3542 within 30 days after the date of approval of the
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`supplement for the patent information to be timely filed (see 21 CFR
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` 3 For the most recent version of a guidance, check the FDA guidance web page at
` https://www.fda.gov/media/128163/download.
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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
`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: 4998594
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` NDA 208700/S-019 and S-023
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` Page 4
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`314.53(c)(2)(ii)). You also must ensure that any changes to your approved NDA that
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`require the submission of a request to remove patent information from the Orange Book
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`are submitted to FDA at the time of approval of the supplement pursuant to 21 CFR
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`314.53(d)(2)(ii)(B) and 314.53(f)(2)(iv).
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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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` If you have any questions, call Emily Pak, Regulatory Health Project Manager, at 301-
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` 837-7531.
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`Sincerely,
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`{See appended electronic signature page}
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`
`Martha Donoghue, M.D.
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`Deputy Director
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`Division of Oncology 2
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`Office of Oncologic Diseases
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`Center for Drug Evaluation and Research
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`ENCLOSURE:
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`• Content of Labeling
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`o Prescribing Information
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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: 4998594
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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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`MARTHA B DONOGHUE
`06/13/2022 05:21:16 PM
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`Reference ID: 4998594
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`(
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