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`DEPARTMENT OF HEALTH & HUMAN SERVICES
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`Public Health Service
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`Food and Drug Administration
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`Rockville, MD 20857
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` NDA APPROVAL
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`NDA 22-253
`NDA 22-254
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`Schwarz Biosciences, Inc.
`Attention: Alan Blumberg
`Senior Director, US Regulatory Affairs
`P.O. Box 110167
`Research Triangle Park, NC 27709
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`Dear Mr. Blumberg:
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`Please refer to your new drug applications (NDAs) dated September 28, 2007, received
`September 28, 2007, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic
`Act (FDCA), for Vimpat (lacosamide) Tablets, 50 mg, 100 mg, 150 mg, and 200 mg, and
`Vimpat (lacosamide) Injection, 200 mg per 20 ml.
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`We acknowledge receipt of your additional submissions dated:
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`November 26, 2007 March 20, 2008 April 30, 2008
`December 13, 2007 April 3, 2008
`May 9, 2008
`January 23, 2008
`April 9, 2008
`May 27, 2008
`February 13, 2008
`April 14, 2008
`June 11, 2008
`February 22, 2008
`April 18, 2008
`July 11, 2008 (2)
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`These new drug applications provide for the use of Vimpat (lacosamide) as follows:
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`• Vimpat (lacosamide) Tablets as adjunctive therapy in the treatment of partial-onset seizures
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`in patients with epilepsy aged 17 years and older.
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`July 17, 2008
`July 30, 2008
`August 1, 2008
`August 14, 2008
`August 27, 2008
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`September 4, 2008
`September 23, 2008
`October 15, 2008
`October 21, 2008
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`• Vimpat (lacosamide) Injection as adjunctive therapy in the treatment of partial-onset seizures
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`in patients with epilepsy aged 17 years and older when oral administration is temporarily not
`feasible.
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`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 text.
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`

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`NDA 22-253
`NDA 22-254
`Page 2
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`Your applications for Vimpat (lacosamide) Tablets and Injection (NDA 22-253, 22-254) were
`not referred to an FDA advisory committee because your products are members of the class of
`previously approved anti-epileptic drugs and the products did not pose unique concerns beyond
`those applicable to other members of this class.
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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
`active ingredients, 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(s) in pediatric patients unless this requirement is waived,
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`deferred, or inapplicable.
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`We are waiving the pediatric study requirement for ages 0 to 1 month for these applications
`because necessary studies are impossible or highly impracticable because there are too few
`children with partial onset seizures in this age group to study.
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`In addition, we are deferring submission of your pediatric studies in partial onset seizures for
`ages 1 month up to 17 years for this application because this product is ready for approval for use
`in adults and the pediatric studies have not been completed.
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`Your deferred pediatric studies required by section 505B(a) of the FDCA are required
`postmarketing studies. The status of these postmarketing studies must be reported annually
`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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`1. Deferred pediatric studies under PREA for the adjunctive treatment of partial onset seizures
`in pediatric patients ages 1 month up to 17 years.
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`Final Report Submission: July 2013
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`Submit final study reports to these NDAs. For administrative purposes, all submissions related
`to these required pediatric postmarketing studies must be clearly designated “Required
`Pediatric Assessment.”
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`RISK EVALUATION AND MITIGATION STRATEGY (REMS) REQUIREMENTS
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`Title IX, Subtitle A, Section 901 of Food and Drug Administration Amendments Act of 2007
`(FDAAA) amends the FDCA to authorize FDA to require the submission of a Risk Evaluation
`and Mitigation Strategy (REMS) if FDA determines that such a strategy is necessary to ensure
`that the benefits of the drug outweigh the risks (section 505-1(a)). This provision took effect on
`March 25, 2008.
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`In accordance with section 505-1 of the FDCA, as one element of a REMS, FDA may require the
`development of a Medication Guide as provided for under 21 CFR Part 208. Pursuant to 21 CFR
`Part 208, FDA has determined that Vimpat (lacosamide) poses a serious and significant public
`health concern requiring the distribution of a Medication Guide. The Medication Guide is
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`

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`NDA 22-253
`NDA 22-254
`Page 3
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`necessary for patients’ safe and effective use of Vimpat (lacosamide). FDA has determined that
`Vimpat (lacosamide) has serious risks of which patients should be made aware because
`information concerning the risks could affect patients' decisions to use Vimpat (lacosamide). In
`addition, patient labeling could help prevent serious adverse effects related to the use of these
`products. Vimpat (lacosamide) may increase the risk of suicidal thoughts or behavior in patients
`taking anti-epileptic drugs for any indication. Under 21 CFR 208, you are responsible for
`ensuring that the Medication Guide is available for distribution to patients who are dispensed
`Vimpat (lacosamide).
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`Your proposed REMS, submitted on October 17, 2008, in an electronic communication, is
`approved. The REMS consists of the Medication Guide included with this letter and the
`timetable for submission of assessments of the REMS included in your October 17, 2008
`submission.
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`Prominently identify submissions containing REMS assessments or proposed modifications of
`the REMS with the following wording in bold capital letters at the top of the first page of the
`submission:
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`• NDA 22-253 & 22-254 REMS ASSESSMENT
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`• NEW SUPPLEMENT FOR NDA 22-253 & 22-254
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`PROPOSED REMS MODIFICATION
`< other supplement identification > [if included]
`<REMS ASSESSMENT> [if included]
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`POSTMARKETING REQUIREMENTS UNDER 505(o)
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`Title IX, Subtitle A, Section 901 of FDAAA amends the FDCA to authorize FDA to require
`holders of approved drug and biological product applications to conduct postmarketing studies
`and clinical trials for certain purposes, if FDA makes certain findings required by the statute
`(section 505(o)(3)(A), 21 U.S.C. 355(o)(3)(A)).
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`We have determined that an analysis of spontaneous postmarketing adverse events reported
`under subsection 505(k)(1) of the FDCA will not be sufficient to assess the known serious risk of
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`developmental neurotoxicity.
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`Furthermore, the new pharmacovigilance system that FDA is required to establish under section
`505(k)(3) has not yet been established and is not sufficient to assess this serious risk.
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`Therefore, based on appropriate scientific data, FDA has determined that you are required,
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`pursuant to section 505(o)(3) of the FDCA, to conduct the following study:
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`2. A nonclinical study in rats to examine the effects of Vimpat (lacosamide) on brain
`development during the prenatal and early postnatal periods using more sensitive techniques
`for assessing central nervous system structure and function than were employed in the
`standard pre- and postnatal development study. You should consider the use of multiple
`daily dosing as a means of achieving higher plasma drug exposures during pregnancy and to
`better mimic the human exposure pattern.
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`

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`NDA 22-253
`NDA 22-254
`Page 4
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`The timetable you have submitted on October 28, 2008 states that you will conduct this study
`according to the following schedule:
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`Within 6 months of approval
`Protocol Submission:
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`Final Report Submission: Within 30 months of approval
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`Submit protocols to your IND 57,939 with a cross-reference letter to these new drug applications
`(NDA) 22-253 and 22-254. Submit final reports to your NDAs 22-253 and 22-254. Please use
`the following designators to label prominently all submissions, including supplements, relating
`to this postmarketing study as appropriate:
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`• Required Postmarketing Protocol under 505(o)
`• Required Postmarketing Final Report under 505(o)
`• Required Postmarketing Correspondence under 505(o)
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`Section 505(o)(3)(E)(ii) of the FDCA requires you to report periodically on the status of any
`study or clinical trial required under this section. This section also requires you to periodically
`report to FDA on the status of any study or clinical trial otherwise undertaken to investigate a
`safety issue. Section 506B of the FDCA, as well as 21 CFR 314.81(b)(2)(vii) requires you to
`report annually on the status of any postmarketing commitments or required studies or clinical
`trials.
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`FDA will consider the submission of your annual report under section 506B and 21 CFR
`314.81(b)(2)(vii) to satisfy the periodic reporting requirement under section 505(o)(3)(E)(ii)
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` provided that you include the elements listed in 505(o) and 21 CFR 314.81(b)(2)(vii). We
`remind you that to comply with 505(o), your annual report must also include a report on the
`status of any study or clinical trial otherwise undertaken to investigate a safety issue. Failure to
`submit an annual report for studies or clinical trials required under 505(o) on the date required
`will be considered a violation of FDCA section 505(o)(3)(E)(ii) and could result in enforcement
`action.
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`POSTMARKETING COMMITMENTS
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`We acknowledge your written commitment to conduct the following postmarketing study as
`described in your submission dated October 28, 2008, as outlined below:
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`3. In vitro data to determine which enzymes may be involved in the metabolism of Vimpat
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`(lacosamide) in addition to CYP2C19.
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`Final Report Submission: within 18 months of approval
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` (b) (4)
` Submit nonclinical and chemistry, manufacturing, and
`Submit the protocol to your IND
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`controls protocols and all study final reports to these NDAs. In addition, under 21 CFR
`314.81(b)(2)(vii) and 314.81(b)(2)(viii), you should include a status summary of each
`commitment in your annual report to these NDAs. The status summary should include expected
`summary completion and final report submission dates, any changes in plans since the last
`annual report, and, for clinical studies, number of patients entered into each study.
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`

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`NDA 22-253
`NDA 22-254
`Page 5
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`All submissions, including supplements, relating to these postmarketing study commitments
`should be prominently labeled:
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`• Postmarketing Study Commitment Protocol
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`• Postmarketing Study Commitment Final Report
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`• Postmarketing Study Commitment Correspondence
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`HIGHLIGHTS WAIVER
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`We are waiving the requirements of 21 CFR 201.57(d)(8) regarding the length of Highlights of
`prescribing information. This waiver applies to all future supplements containing revised
`labeling unless we notify you otherwise.
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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, please submit the
`content of labeling [21 CFR 314.50(l)] in structured product labeling (SPL) format as described
`at http://www.fda.gov/oc/datacouncil/spl.html that is identical to the enclosed labeling (text for
`the package insert and Medication Guide). Upon receipt, we will transmit that version to the
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`National Library of Medicine for public dissemination. For administrative purposes, please
`designate this submission, “SPL for approved NDA 22-253 and NDA 22-254.”
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`CARTON AND IMMEDIATE CONTAINER LABELS
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`Submit final printed carton and container labels as soon as they are available, but no more than
`30 days after they are printed. Please submit these labels electronically according to the
`guidance for industry titled Providing Regulatory Submissions in Electronic Format – Human
`Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications
`(October 2005). Alternatively, you may submit 12 paper copies, with 6 of the copies individually
`mounted on heavy-weight paper or similar material. For administrative purposes, designate this
`submission “Final Printed Carton and Container Labels for approved NDA 22-253 and
`NDA 22-254” Approval of this submission by FDA is not required before the labeling is used.
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`In addition, we note your agreement on October 28, 2008 to address and make the following
`changes into your carton and immediate container labels:
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`General
`(b) (4)
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`NDA 22-253
`NDA 22—253
`NDA 22-254
`NDA 22—254
`Page 6
`Page 6
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`(b) (4)
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`(b) (4)
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`(b) (4)
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`NDA 22-253
`NDA 22-254
`Page 7
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`(b) (4)
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`Marketing the products with FPL that is not identical to the approved labeling text including the
`changes noted above may render the product misbranded and an unapproved new drug.
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`CONTROLLED SUBSTANCE CLASS
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` We have recommended that this product be scheduled under the Controlled Substances Act. We
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`remind you of the following statement that appears on the Form FDA 356h, “If this application
`applies to a drug product that FDA has proposed for scheduling under the Controlled Substances
`Act, I agree not to market the product until the Drug Enforcement Administration makes a final
`scheduling decision.” Once a final scheduling decision is made, your label must be amended to
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`reflect the schedule.
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`EXPIRATION DATE (Injection)
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`We grant the proposed 36 month drug product expiry, when stored at controlled room
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`temperature, for lacosamide 200 mg/20 mL injection packaged in 20 mL type I colorless glass
`vials with a grey rubber stopper coated with a
`and aluminum overseal.
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`PROMOTIONAL MATERIALS
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`You may request advisory comments on proposed introductory advertising and promotional
`labeling. To do so, submit, in triplicate, a cover letter requesting advisory comments, the
`proposed materials in draft or mock-up form with annotated references, and the package insert(s)
`to:
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`Food and Drug Administration
`Center for Drug Evaluation and Research
`Division of Drug Marketing, Advertising, and Communications
`5901-B Ammendale Road
`Beltsville, MD 20705-1266
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`As required under 21 CFR 314.81(b)(3)(i), you must submit final promotional materials, and the
`package insert(s), at the time of initial dissemination or publication, accompanied by a Form
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`FDA 2253. For instruction on completing the Form FDA 2253, see page 2 of the Form. For
`more information about submission of promotional materials to the Division of Drug Marketing,
`Advertising, and Communications (DDMAC), see www.fda.gov/cder/ddmac.
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` LETTERS TO HEALTH CARE PROFESSIONALS
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`If you issue a letter communicating important safety related information about this drug product
`(i.e., a “Dear Health Care Professional” letter), we request that you submit an electronic copy of
`the letter to both this NDA and to the following address:
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`(b) (4)
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`

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`NDA 22-253
`NDA 22-254
`Page 8
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`MedWatch
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`Food and Drug Administration
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`Suite 12B05
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`5600 Fishers Lane
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`Rockville, MD 20857
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`REPORTING REQUIREMENTS
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`We remind you that you must comply with reporting requirements for an approved NDA (21
`CFR 314.80 and 314.81).
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`MEDWATCH-TO-MANUFACTURER PROGRAM
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`The MedWatch-to-Manufacturer Program provides manufacturers with copies of serious adverse
`event reports that are received directly by the FDA. New molecular entities and important new
`biologics qualify for inclusion for three years after approval. Your firm is eligible to receive
`copies of reports for this product. To participate in the program, please see the enrollment
`instructions and program description details at www.fda.gov/medwatch/report/mmp.htm.
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`If you have any questions, call Jacqueline H. Ware, Pharm.D., Supervisory Regulatory Project
`Manager, at (301) 796-1160.
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`Sincerely,
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`{See appended electronic signature page}
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`Ellis F. Unger, M.D.
`Deputy Director (Acting)
`Office of Drug Evaluation I
`Center for Drug Evaluation and Research
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`Enclosures (FDA Approved Labeling Text, Medication Guide, and REMS document)
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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/
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`---------------------
`Ellis Unger
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`10/28/2008 08:00:13 PM
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