~... .. ~ ~
`( ~DEPARTMENT OF HEALTH AND HUMAN SERVICES
`<~~~t._
`~...(J
`
`NDA 022253/S-026 & S-027
`NDA 022254/S-019 & S-020
`NDA 022255/S-012 & S-013
`
`UCB, Inc.
`Attention: Susan Tegtmeyer, M.S .
`Associate Director, Regulat01y Affairs
`1950 Lake Park Drive,
`Smyma, Georgia 30080
`
`Dear Ms. Tegtmeyer:
`
`Food and Drug Administration
`Silver Spring MD 20993
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`SUPPLEMENT APPROVAL
`
`Please refer to your Supplemental New Dmg Applications (sNDAs) submitted under section
`505(b) of the Federal Food, Dmg, and Cosmetic Act (FDCA) for the following:
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`Application
`
`NDA 022253/S-026
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`NDA 02225 4/S-020
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`NDA 022255/S-013
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`Product Name
`Vimpat (lacosamide)
`Tablets
`Vimpat (lacosamide)
`Injection
`Vimpat (lacosamide)
`Oral Solution
`
`Submitted on:
`
`Received on:
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`July31 , 2013
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`August 1, 2013
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`July31 , 2013
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`August 1, 2013
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`July31 , 2013
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`August 1, 2013
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`These supplements propose:
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`The use ofVimpat as monotherapy (conversion to and initial) in the u·eatment ofpattial-onset
`seizures in patients with epilepsy age 17 years an d older.
`
`Application
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`NDA 022253/S-027
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`NDA 02225 4/S-019
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`NDA 022255/S-012
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`Product Name
`Vimpat (lacosamide)
`Tablets
`Vimpat (lacosamide)
`Injection
`Vimpat (lacosamide)
`Oral Solution
`
`Submitted on:
`
`Received on:
`
`July31 , 2013
`
`August 1, 2013
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`July31 , 2013
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`August 1, 2013
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`July31 , 2013
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`August 1, 2013
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`These supplements propose:
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`1. The initiation of VIMP AT therapy with a loading dose (oral or inu·avenous) of 200 mg.
`2. A lower liinit of 15 minutes for the infusion duration.
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`Refe rence ID: 36194 12
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`

`

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` NDA 022253/S-026 & S-027
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` NDA 022254/S-019 & S-020
`NDA 022255/S-012 & S-013
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` Page 2
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` We acknowledge receipt of your amendments dated October 3, 2013; October 11, 2013; October
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` 22, 2013; November 4, 2013; November 25, 2013; November 26, 2013; January 24, 2014;
` February 4, 2014; February 6, 2014; February 19, 2014; March 6, 2014; March 31, 2014; April
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` 25, 2014; May 2, 2014; May 9, 2014; May 15, 2014; May 23, 2014; May 27, 2014; May 30,
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` 2014; June 26, 2014; June 30, 2014; July 22, 2014, July 25, 2014; and August 7, 2014.
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`APPROVAL & LABELING
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`We have completed our review of this supplemental application. It is approved, effective on the
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`date of this letter, for use as recommended in the enclosed, agreed-upon labeling text.
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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
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`labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format using the FDA
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`automated drug registration and listing system (eLIST), as described at
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`http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Content
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`of labeling must be identical to the enclosed labeling (text for the package insert and Medication
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`Guide), with the addition of any labeling changes in pending “Changes Being Effected” (CBE)
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`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
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`“SPL Standard for Content of Labeling Technical Qs and As at
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`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 includes labeling changes
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`for this NDA, including CBE supplements for which FDA has not yet issued an action letter,
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`with the content of labeling [21 CFR 314.50(l)(1)(i)] in MS Word format, that includes the
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`changes approved in this supplemental application, as well as annual reportable changes and
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`annotate each change. To facilitate review of your submission, provide a highlighted or marked-
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`up copy that shows all changes, as well as a clean Microsoft Word version. The marked-up copy
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`should provide appropriate annotations, including supplement number(s) and annual report
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`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 new
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`active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of
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`administration are required to contain an assessment of the safety and effectiveness of the
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`product for the claimed indication(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`Reference ID: 3619412
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`

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` NDA 022253/S-026 & S-027
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` NDA 022254/S-019 & S-020
`NDA 022255/S-012 & S-013
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` Page 3
` We are waiving the pediatric studies requirement for ages 0 to 1 month because necessary
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` studies are impossible or highly impracticable. This is because studies are challenging in
` children < 1month due to small number of patients and difficulty of diagnosis in this age group.
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`We are deferring submission of your pediatric studies for ages ≥ 1 month to < 17 years for this
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`application because this product is ready for approval for use in adults and the pediatric studies
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`have not been completed.
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`Your deferred pediatric studies required by section 505B(a) of the FDCA are required
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`postmarketing studies. The status of these postmarketing studies must be reported annually
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`according to 21 CFR 314.81 and section 505B(a)(3)(B) of the FDCA. These required studies are
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`listed below.
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`2773-1 A PK-PD bridging simulation study must be conducted to determine the
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`appropriate lacosamide monotherapy regimen for the treatment of partial-onset
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`seizures in the pediatric population ≥ 1 month to < 17 years of age, and to support
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`efficacy by extrapolation based on PK and efficacy data of lacosamide for
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`adjunctive therapy for partial-onset seizures in pediatrics and adults, and efficacy
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`for monotherapy for partial-onset seizures in adults. If the exposure-response
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`relationship in younger children, e.g., less than 4 years old, is different from the
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`older children and adult populations, this will be considered, and changes will be
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`made accordingly.
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`Final Protocol Submission: 02/2018 (Statistical Analysis Plan)
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`06/2018
`Study Completion:
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`Final Report Submission:
`12/2018
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`2773-2 An open-label safety and tolerability study using lacosamide as monotherapy in
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`pediatric patients ≥ 1 month to < 17 years of age.
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`Final Protocol Submission: 02/2019
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`02/2023
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`Study Completion:
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`Final Report Submission:
`08/2023
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`2774-1 A safety study of replacement of oral dosing with intravenous dosing
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`administered over 30 to 60 minutes in pediatric patients ≥ 1 month to < 17 years
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`of age with partial-onset seizures. If safety is acceptable, a replacement study at a
`faster rate of infusion (15 minutes) must be conducted in this population. Sparse
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`PK samples must be collected to evaluate the pharmacokinetics of lacosamide and
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`its metabolite using PPK approach in this population.
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`Final Protocol Submission: 07/2015
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`08/2017
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`Study Completion:
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`Final Report Submission:
`01/2018
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`Reference ID: 3619412
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`

`

`
` NDA 022253/S-026 & S-027
`
` NDA 022254/S-019 & S-020
`NDA 022255/S-012 & S-013
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` Page 4
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` 2774-2 A study that will examine safety and tolerability of an oral loading dose that will
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` allow a more rapid achievement of the final recommended therapeutic dose in
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` pediatric patients ≥ 1 month to < 17 years of age.
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`Final Protocol Submission: 03/2019
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`09/2020
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`Study Completion:
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`Final Report Submission:
`03/2021
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`2774-3 A study that will examine safety and tolerability of an intravenous loading dose
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`that will allow a more rapid achievement of steady-state exposures of the final
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`recommended therapeutic dose in pediatric patients ≥ 1 month to < 17 years of
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`age.
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`Final Protocol Submission: 03/2019
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`09/2020
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`Study Completion:
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`Final Report Submission:
`03/2021
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`Please allow for adequate time for Agency review and comment on each of the protocols, and for
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`agreement on the protocols, prior to the final protocol submission dates.
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`Submit the protocols to IND 057939 and IND 073809, with a cross-reference letter to this NDA.
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`Reports of these required pediatric postmarketing studies must be submitted as a new drug
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`application (NDA) or as a supplement to your approved NDA with the proposed labeling
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`changes you believe are warranted based on the data derived from these studies. When
`submitting the reports, please clearly mark your submission "SUBMISSION OF REQUIRED
`PEDIATRIC ASSESSMENTS" in large font, bolded type at the beginning of the cover letter of
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`the submission.
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`Reference ID: 3619412
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`

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` NDA 022253/S-026 & S-027
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` NDA 022254/S-019 & S-020
`NDA 022255/S-012 & S-013
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` Page 5
` PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
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`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
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` (3) the package insert(s) to:
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`
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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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`You must submit final promotional materials and package insert(s), accompanied by a Form
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`FDA 2253, at the time of initial dissemination or publication [21 CFR 314.81(b)(3)(i)]. Form
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`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
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`http://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM375154.pdf. For
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`more information about submission of promotional materials to the Office of Prescription Drug
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`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
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`(21 CFR 314.80 and 314.81).
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`If you have any questions, call Stephanie N. Parncutt, MHA, Regulatory Project Manager, at
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`(301) 796-4098.
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`Sincerely,
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`{See appended electronic signature page}
`
`
`Eric Bastings, M.D.
`
`Deputy Director
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`Division of Neurology Products
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`Office of Drug Evaluation I
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`Center for Drug Evaluation and Research
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`ENCLOSURE(S):
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`Content of Labeling
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`Reference ID: 3619412
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`

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`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`ERIC P BASTINGS
`08/29/2014
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`Reference ID: 3619412
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`