CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`
`APPLICATION NUMBER:
`
`125390Orig1s000
`
`ADMINISTRATIVE and CORRESPONDENCE
`DOCUMENTS
`
`
`
`
`

`

`PEDIATRIC PAGE
`(Complete for all filed original applications and efficacy supplements)
`NDA/BLA#: BLA 125390
`Supplement Number:
`NDA Supplement Type (e.g. SE5):
`Division Name:DMEP
`PDUFA Goal Date: 2/24/14
`Stamp Date: 3/27/2013
`Proprietary Name: Myalept
`Established/Generic Name: metreleptin
`Dosage Form:
`for subcutaneous injection
`Applicant/Sponsor:
`Amylin Pharmaceuticals,LLC; (a wholly owned subsidiary of Bristol Myers Squibb
`Indication(s) previously approved (please complete this question for supplements and Type 6 NDAs only):
`(1)
`(2)
`(3)
`(4)
`Pediatric use for each pediatric subpopulation must be addressed for each indication covered by current
`application under review. A Pediatric Page must be completed for each indication.
`Number of indications for this pending application(s):1
`(Attach a completed Pediatric Page for each indication in current application.)
`Indication: as an adjunct to diet as replacement therapy to treat the complications of leptin
`deficiency in patients with congenital or acquired generalized lipodystrophy (1).
`Q1: Is this application in response to a PREA PMR?
`Yes
`Continue
`No
`Please proceed to Question 2.
`PMR #:
`
`Supplement #:
`If Yes, NDA/BLA#:
`Does the division agree that this is a complete response to the PMR?
`Yes. Please proceed to Section D.
`No. Please proceed to Question 2 and complete the Pediatric Page, as applicable.
`Q2: Does this application provide for (If yes, please check all categories that apply and proceed to the next
`question):
`active ingredient(s) (includes new combination);
`(a) NEW
`route of administration?*
`regimen; or
`No. PREA does not apply. Skip to signature block.
`(b)
`* Note for CDER: SE5, SE6, and SE7 submissions may also trigger PREA.
`Q3: Does this indication have orphan designation?
`Yes. PREA does not apply. Skip to signature block.
`No. Please proceed to the next question.
`Q4: Is there a full waiver for all pediatric age groups for this indication (check one)?
`Yes: (Complete Section A.)
`No: Please check all that apply:
`Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`Deferred for some or all pediatric subpopulations (Complete Sections C)
`Completed for some or all pediatric subpopulations (Complete Sections D)
`Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`Extrapolation in One or More Pediatric Age Groups (Complete Section F)
`
`dosing
`
`indication(s);
`
`dosage form;
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`(Please note that Section F may be used alone or in addition to Sections C, D, and/or E.)
`Section A: Fully Waived Studies (for all pediatric age groups)
`Reason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
`Necessary studies would be impossible or highly impracticable because:
`Disease/condition does not exist in children
`Too few children with disease/condition to study
`Other (e.g., patients geographically dispersed):
`Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial number of pediatric patients.
`Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`the labeling.)
`Justification attached.
`If studies are fully waived, then pediatric information is complete for this indication. If there is another
`indication, please complete another Pediatric Page for each indication. Otherwise, this Pediatric Page is
`complete and should be signed.
`Section B: Partially Waived Studies (for selected pediatric subpopulations)
`Check subpopulation(s) and reason for which studies are being partially waived (fill in applicable criteria below):
`Note: If Neonate includes premature infants, list minimum and maximum age in “gestational age” (in weeks).
`Reason (see below for further detail):
`Not meaningful
`therapeutic
`benefit*
`
`minimum
`
`maximum
`
`Page 2
`
`Not
`feasible#
`
`Ineffective or
`unsafe†
`
`Formulation
`failed∆
`
`wk. mo.
`wk. mo.
`Neonate
`yr. mo.
`yr. mo.
`Other
`yr. mo.
`yr. mo.
`Other
`yr. mo.
`yr. mo.
`Other
`yr. mo.
`yr. mo.
`Other
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`# Not feasible:
`Necessary studies would be impossible or highly impracticable because:
`Disease/condition does not exist in children
`Too few children with disease/condition to study
`Other (e.g., patients geographically dispersed):
`* Not meaningful therapeutic benefit:
`Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients in this/these pediatric subpopulation(s) AND is not likely to be used in a substantial number of
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`Page 3
`
`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`pediatric patients in this/these pediatric subpopulation(s).
`† Ineffective or unsafe:
`Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if studies
`are partially waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective and unsafe in all pediatric subpopulations
`(Note: if studies are partially waived on this ground, this information must be included in the labeling.)
`∆ Formulation failed:
`Applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may only cover
`the pediatric subpopulation(s) requiring that formulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailing why a pediatric formulation cannot be developed. This
`submission will be posted on FDA's website if waiver is granted.)
`Justification attached.
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been deferred (if so, proceed to Sections C and complete the PeRC Pediatric Plan
`Template); (2) submitted studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additional studies in other age groups that are not needed because the
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Section E); and/or (4)
`additional studies in other age groups that are not needed because efficacy is being extrapolated (if so,
`proceed to Section F). Note that more than one of these options may apply for this indication to cover all of the
`pediatric subpopulations.
`
`Section C: Deferred Studies (for selected pediatric subpopulations).
`Check pediatric subpopulation(s) for which pediatric studies are being deferred (and fill in applicable reason
`below):
`
`Deferrals (for each or all age groups):
`
`Population
`
`minimum
`
`maximum
`
`Reason for Deferral
`
`Ready
`for
`Approval
`in Adults
`
`Need
`Additional
`Adult Safety or
`Efficacy Data
`
`Other
`Appropriate
`Reason
`(specify
`below)*
`
`Applicant
`Certification
`†
`
`Received
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric
`Populations
`Date studies are due (mm/dd/yy):
`
`0 yr. 0 mo.
`
`16 yr. 11 mo.
`
`Are the indicated age ranges (above) based on weight (kg)?
`Are the indicated age ranges (above) based on Tanner Stage?
`
`No;
`No;
`
`Yes.
`Yes.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`Page 4
`
`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`* Other Reason:
`† Note: Studies may only be deferred if an applicant submits a certification of grounds for deferring the studies,
`a description of the planned or ongoing studies, evidence that the studies are being conducted or will be
`conducted with due diligence and at the earliest possible time, and a timeline for the completion of the studies.
`If studies are deferred, on an annual basis applicant must submit information detailing the progress made in
`conducting the studies or, if no progress has been made, evidence and documentation that such studies will be
`conducted with due diligence and at the earliest possible time. This requirement should be communicated to
`the applicant in an appropriate manner (e.g., in an approval letter that specifies a required study as a post-
`marketing commitment.)
`If all of the pediatric subpopulations have been covered through partial waivers and deferrals, Pediatric Page is
`complete and should be signed. If not, complete the rest of the Pediatric Page as applicable.
`Section D: Completed Studies (for some or all pediatric subpopulations).
`
`Population
`
`minimum
`
`maximum
`
`Pediatric subpopulation(s) in which studies have been completed (check below):
`PeRC Pediatric Assessment form
`attached?.
`No
`No
`No
`No
`No
`No
`
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric Subpopulations
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`0 yr. 0 mo.
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`16 yr. 11 mo.
`
`Yes
`Yes
`Yes
`Yes
`Yes
`Yes
`
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Note: If there are no further pediatric subpopulations to cover based on partial waivers, deferrals and/or
`completed studies, Pediatric Page is complete and should be signed. If not, complete the rest of the Pediatric
`Page as applicable.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`
`Page 5
`
`Section E: Drug Appropriately Labeled (for some or all pediatric subpopulations):
`
`Additional pediatric studies are not necessary in the following pediatric subpopulation(s) because product is
`appropriately labeled for the indication being reviewed:
`Population
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric Subpopulations
`
`maximum
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`16 yr. 11 mo.
`
`minimum
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`0 yr. 0 mo.
`
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`If all pediatric subpopulations have been covered based on partial waivers, deferrals, completed studies, and/or
`existing appropriate labeling, this Pediatric Page is complete and should be signed. If not, complete the rest of
`the Pediatric Page as applicable.
`
`Section F: Extrapolation from Other Adult and/or Pediatric Studies (for deferred and/or completed studies)
`Note: Pediatric efficacy can be extrapolated from adequate and well-controlled studies in adults and/or other
`pediatric subpopulations if (and only if) (1) the course of the disease/condition AND (2) the effects of the
`product are sufficiently similar between the reference population and the pediatric subpopulation for which
`information will be extrapolated. Extrapolation of efficacy from studies in adults and/or other children usually
`requires supplementation with other information obtained from the target pediatric subpopulation, such as
`pharmacokinetic and safety studies. Under the statute, safety cannot be extrapolated.
`
`Pediatric studies are not necessary in the following pediatric subpopulation(s) because efficacy can be
`extrapolated from adequate and well-controlled studies in adults and/or other pediatric subpopulations:
`Extrapolated from:
`Other Pediatric
`Studies?
`
`Adult Studies?
`
`Population
`
`minimum
`
`maximum
`
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric
`Subpopulations
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`
`0 yr. 0 mo.
`
`16 yr. 11 mo.
`
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Note: If extrapolating data from either adult or pediatric studies, a description of the scientific data supporting
`the extrapolation must be included in any pertinent reviews for the application.
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`If there are additional indications, please complete the attachment for each one of those indications.
`Otherwise, this Pediatric Page is complete and should be signed and entered into DFS or DARRTS as
`appropriate after clearance by PeRC.
`This page was completed by:
`
`Page 6
`
`{See appended electronic signature page}
`___________________________________
`Regulatory Project Manager
`
`(Revised: 6/2008)
`
`NOTE: If you have no other indications for this application, you may delete the attachments from this
`document.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`Attachment A
`(This attachment is to be completed for those applications with multiple indications only.)
`
`Page 7
`
`Indication #2:
`Q1: Does this indication have orphan designation?
`Yes. PREA does not apply. Skip to signature block.
`No. Please proceed to the next question.
`Q2: Is there a full waiver for all pediatric age groups for this indication (check one)?
`Yes: (Complete Section A.)
`No: Please check all that apply:
`Partial Waiver for selected pediatric subpopulations (Complete Sections B)
`Deferred for some or all pediatric subpopulations (Complete Sections C)
`Completed for some or all pediatric subpopulations (Complete Sections D)
`Appropriately Labeled for some or all pediatric subpopulations (Complete Sections E)
`Extrapolation in One or More Pediatric Age Groups (Complete Section F)
`(Please note that Section F may be used alone or in addition to Sections C, D, and/or E.)
`Section A: Fully Waived Studies (for all pediatric age groups)
`Reason(s) for full waiver: (check, and attach a brief justification for the reason(s) selected)
`Necessary studies would be impossible or highly impracticable because:
`Disease/condition does not exist in children
`Too few children with disease/condition to study
`Other (e.g., patients geographically dispersed):
`Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients AND is not likely to be used in a substantial number of pediatric patients.
`Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are fully waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are fully waived on this ground, this information must be included in
`the labeling.)
`Justification attached.
`If studies are fully waived, then pediatric information is complete for this indication. If there is another
`indication, please complete another Pediatric Page for each indication. Otherwise, this Pediatric Page is
`complete and should be signed.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`
`Page 8
`
`Section B: Partially Waived Studies (for selected pediatric subpopulations)
`Check subpopulation(s) and reason for which studies are being partially waived (fill in applicable criteria below):
`Note: If Neonate includes premature infants, list minimum and maximum age in “gestational age” (in weeks).
`Reason (see below for further detail):
`Not meaningful
`therapeutic
`benefit*
`
`minimum
`
`maximum
`
`Not
`feasible#
`
`Ineffective or
`unsafe†
`
`Formulation
`failed∆
`
`wk. mo.
`wk. mo.
`Neonate
`yr. mo.
`yr. mo.
`Other
`yr. mo.
`yr. mo.
`Other
`yr. mo.
`yr. mo.
`Other
`yr. mo.
`yr. mo.
`Other
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Reason(s) for partial waiver (check reason corresponding to the category checked above, and attach a brief
`justification):
`# Not feasible:
`Necessary studies would be impossible or highly impracticable because:
`Disease/condition does not exist in children
`Too few children with disease/condition to study
`Other (e.g., patients geographically dispersed):
`* Not meaningful therapeutic benefit:
`Product does not represent a meaningful therapeutic benefit over existing therapies for pediatric
`patients in this/these pediatric subpopulation(s) AND is not likely to be used in a substantial number of
`pediatric patients in this/these pediatric subpopulation(s).
`† Ineffective or unsafe:
`Evidence strongly suggests that product would be unsafe in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective in all pediatric subpopulations (Note: if
`studies are partially waived on this ground, this information must be included in the labeling.)
`Evidence strongly suggests that product would be ineffective and unsafe in all pediatric
`subpopulations (Note: if studies are partially waived on this ground, this information must be
`included in the labeling.)
`∆ Formulation failed:
`Applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for
`this/these pediatric subpopulation(s) have failed. (Note: A partial waiver on this ground may only cover
`the pediatric subpopulation(s) requiring that formulation. An applicant seeking a partial waiver on this
`ground must submit documentation detailing why a pediatric formulation cannot be developed. This
`submission will be posted on FDA's website if waiver is granted.)
`Justification attached.
`For those pediatric subpopulations for which studies have not been waived, there must be (1) corresponding
`study plans that have been deferred (if so, proceed to Section C and complete the PeRC Pediatric Plan
`Template); (2) submitted studies that have been completed (if so, proceed to Section D and complete the
`PeRC Pediatric Assessment form); (3) additional studies in other age groups that are not needed because the
`drug is appropriately labeled in one or more pediatric subpopulations (if so, proceed to Section E); and/or (4)
`additional studies in other age groups that are not needed because efficacy is being extrapolated (if so,
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`Page 9
`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`proceed to Section F).. Note that more than one of these options may apply for this indication to cover all of the
`pediatric subpopulations.
`
`Section C: Deferred Studies (for some or all pediatric subpopulations).
`Check pediatric subpopulation(s) for which pediatric studies are being deferred (and fill in applicable reason
`below):
`
`Deferrals (for each or all age groups):
`
`Population
`
`minimum
`
`maximum
`
`Reason for Deferral
`
`Ready
`for
`Approval
`in Adults
`
`Need
`Additional
`Adult Safety or
`Efficacy Data
`
`Other
`Appropriate
`Reason
`(specify
`below)*
`
`Applicant
`Certification
`†
`
`Received
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric
`Populations
`Date studies are due (mm/dd/yy):
`
`0 yr. 0 mo.
`
`16 yr. 11 mo.
`
`No;
`No;
`
`Yes.
`Yes.
`
`Are the indicated age ranges (above) based on weight (kg)?
`Are the indicated age ranges (above) based on Tanner Stage?
`* Other Reason:
`† Note: Studies may only be deferred if an applicant submits a certification of grounds for deferring the studies,
`a description of the planned or ongoing studies, evidence that the studies are being conducted or will be
`conducted with due diligence and at the earliest possible time, and a timeline for the completion of the studies.
`If studies are deferred, on an annual basis applicant must submit information detailing the progress made in
`conducting the studies or, if no progress has been made, evidence and documentation that such studies will be
`conducted with due diligence and at the earliest possible time. This requirement should be communicated to
`the applicant in an appropriate manner (e.g., in an approval letter that specifies a required study as a post-
`marketing commitment.)
`If all of the pediatric subpopulations have been covered through partial waivers and deferrals, Pediatric Page is
`complete and should be signed. If not, complete the rest of the Pediatric Page as applicable.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`10
`Section D: Completed Studies (for some or all pediatric subpopulations).
`
`Page
`
`Population
`
`minimum
`
`maximum
`
`Pediatric subpopulation(s) in which studies have been completed (check below):
`PeRC Pediatric Assessment form
`attached?
`No
`No
`No
`No
`No
`No
`
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric Subpopulations
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`0 yr. 0 mo.
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`16 yr. 11 mo.
`
`Yes
`Yes
`Yes
`Yes
`Yes
`Yes
`
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Note: If there are no further pediatric subpopulations to cover based on partial waivers, deferrals and/or
`completed studies, Pediatric Page is complete and should be signed. If not, complete the rest of the Pediatric
`Page as applicable.
`
`Section E: Drug Appropriately Labeled (for some or all pediatric subpopulations):
`
`Additional pediatric studies are not necessary in the following pediatric subpopulation(s) because product is
`appropriately labeled for the indication being reviewed:
`Population
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric Subpopulations
`
`maximum
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`16 yr. 11 mo.
`
`minimum
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`0 yr. 0 mo.
`
`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`If all pediatric subpopulations have been covered based on partial waivers, deferrals, completed studies, and/or
`existing appropriate labeling, this Pediatric Page is complete and should be signed. If not, complete the rest of
`the Pediatric Page as applicable.
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`NDA/BLA# BLA 125390BLA 125390BLA 125390BLA 125390BLA 125390
`11
`
`Page
`
`Section F: Extrapolation from Other Adult and/or Pediatric Studies (for deferred and/or completed studies)
`Note: Pediatric efficacy can be extrapolated from adequate and well-controlled studies in adults and/or other
`pediatric subpopulations if (and only if) (1) the course of the disease/condition AND (2) the effects of the
`product are sufficiently similar between the reference population and the pediatric subpopulation for which
`information will be extrapolated. Extrapolation of efficacy from studies in adults and/or other children usually
`requires supplementation with other information obtained from the target pediatric subpopulation, such as
`pharmacokinetic and safety studies. Under the statute, safety cannot be extrapolated.
`
`Pediatric studies are not necessary in the following pediatric subpopulation(s) because efficacy can be
`extrapolated from adequate and well-controlled studies in adults and/or other pediatric subpopulations:
`Extrapolated from:
`Other Pediatric
`Studies?
`
`Adult Studies?
`
`Population
`
`minimum
`
`maximum
`
`Neonate
`Other
`Other
`Other
`Other
`All Pediatric
`Subpopulations
`
`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
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`wk. mo.
`yr. mo.
`yr. mo.
`yr. mo.
`yr. mo.
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`0 yr. 0 mo.
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`16 yr. 11 mo.
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`Yes.
`No;
`Are the indicated age ranges (above) based on weight (kg)?
`Yes.
`No;
`Are the indicated age ranges (above) based on Tanner Stage?
`Note: If extrapolating data from either adult or pediatric studies, a description of the scientific data supporting
`the extrapolation must be included in any pertinent reviews for the application.
`
`If there are additional indications, please copy the fields above and complete pediatric information as
`directed. If there are no other indications, this Pediatric Page is complete and should be entered into DFS
`or DARRTS as appropriate after clearance by PeRC.
`
`This page was completed by:
`
`{See appended electronic signature page}
`___________________________________
`Regulatory Project Manager
`
`FOR QUESTIONS ON COMPLETING THIS FORM CONTACT THE PEDIATRIC AND MATERNAL HEALTH
`STAFF at 301-796-0700
`
`(Revised: 6/2008)
`
`IF THERE ARE QUESTIONS, PLEASE CONTACT THE CDER PMHS VIA EMAIL (cderpmhs@fda.hhs.gov) OR AT 301-796-0700.
`
`Reference ID: 3455233
`
`

`

`---------------------------------------------------------------------------------------------------------
`This is a representation of an electronic record that was signed
`electronically and this page is the manifestation of the electronic
`signature.
`---------------------------------------------------------------------------------------------------------
`/s/
`----------------------------------------------------
`
`PATRICIA J MADARA
`02/17/2014
`
`Reference ID: 3455233
`
`

`

`Amylin Pharmaceuticals, Inc.
`Metreleptin BLA STN125390
`
`MODULE 1
`Page 1
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`1.3.3 Debarment Certification
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`Metreleptin BLA STN125390
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`In compliance with the Section 306(k) of the Federal Food, Drug, and Cosmetic Act
`
`(the Act), 21 U.S.C. §335a(k), as amended by the Generic Drug Enforcement Act of 1992,
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`we, Amylin Pharmaceuticals, Inc., state the following with respect to this Biologics License
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`Application.
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`Amylin Pharmaceuticals, Inc. hereby certifies that it did not and will not use in any capacity
`the services of any person debarred under section 306 of the Federal Food, Drug, and
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`Cosmetic Act in connection with this application.
`
` /l/'/{_,/2a,>p
`
`Lloyd A. Rowland
`Vice President
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`Chief Compliance Officer
`
`Date
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`

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`ACTION PACKAGE CHECKLIST
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`APPLICATION INFORMATION1
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`NDA #
`BLA # 125390
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`NDA Supplement #
`BLA Supplement #
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`IfNDA, Efficacy Supplement Type.
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`Applicant: Amylin Pharmaceuticals, LLC
`Agent for Applicant (if applicable):
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`Division: DMEP
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`Proprietary Name: Myalept
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`Establlshed/Proper Name: metreleptm
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`subcutaneous injection
`Dosage Form:
`RPM: Patricia Madara
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`505(b)(2) Original NDAs and 505(b)(2) NDA supplements:
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`NDAs and NDA Efficacy Supplements:
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`NDA Application Type: X 505(b)(1) [j 505(b)(2)
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`Efficacy Supplement:
`I] 505(b)(1) E] 505(b)(2)
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`(For additional information regarding 505(b)(2)s,
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`
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`please refer to
`ht_tp://inside.fda.gov:9003/CDER/OfficeofNewDrugs/I
`
`mmediateOffice/Re gplatogAffairsTeam/ucmOZ7499.
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`hm)
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`Listed drug(s) relied upon for approval (include NDA #(s) and drug
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`name(s)):
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`, Provide a brief explanation ofhow thisproduct is different from thefl' "ted
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`E This application doesvnot reply upon a listed drug.
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`~
`This application relies on literature.
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`D This application relies on a final OTC monograph.
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`D This application relies on (explain)
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`A For ALL (b)(2) applications, two months pr1ior:t El
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`to CDER 0ND IO for clearance. Finalize the 505(b)(2) 9,,,
`draf
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`Assessment at the time of the approval action.
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`0n the day of approval, check the Orange Book again for any new
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`patents or pediatric exclusivity.
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`E] No changes D Updated Date of check:
` If pediatric exclusivity has been granted or the pediatric information in
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`the labeling of the listed drug changed, determine whether pediatric
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`information needs to be added to or deleted from the labeling of this
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`drug.
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`Proposed action
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`User Fee Goal Date1s 2/24/2014
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`Previous actions (specifi) type and datefor each action taken)
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`l The Application Information Section is (only) a checklist. The Contents of Action Package Section (beginning on page 5) lists
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`, documents to be included in the Action Package.
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`‘ For resubmissions, (b)(2) applications must be cleared before the action, but it is not necessary to resubmit the drafi 505(b)(2)
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`Assessment to CDER 0ND 10 unless the Assessment has been substantively revised (e. g., nrew listed drug, patent certification
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`revised).
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`
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`Version: 12/09/2013
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`

`

`
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`BLA #125390
`
`Page 2
`O
`0.0
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`If accelerated approval or approval based on efficacy studies in animals, were promotional
`materials received?
`
`
`Note: Promotional materials to be used within 120 days after approval must have been
`
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`submitted (for exceptions, see
`http://www.fda.ng/downloads/DruggGuidanceComphangeRegulatgflInformation/Guida
`
`
`
`
`. If not submitted exlainnces/ucm0699 5.
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`D Received
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`Review priority: D Standard X Priority
`Chemical classification (new NDAs only):
`
`XX Fast Track
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`XX Rolling Review
`XX Orphan drug designation
`U Breakthrough Therapy designation
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`Rx-to-OTC full switch
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`Rx-to-OTC partial switch
`Direct—to-OTC
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`NDAs: Subpart H
`
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`[3 Restricted distribution (21 CFR 31
`Subpart I
`'
`U Approval based on animal Studies
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`B Submitted in response to a PMR
`-
`.:_
`i
`I
`' Vi
`7 i"?-
`D Submitted in response to a PMC
`n
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`‘-
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`H
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`>
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`D Submitted in response to a Pediatric Written Re'q'ues"
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`‘ xComments:
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`;:-_;-,
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`,_
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`.._
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`'9' BLAs only. Is the product subject to official FDAlotreleaseper2_lCFR 6l0.2
`(approvals only)
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`- Press Officenotifiedofaction(byOEP)
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`XX HHS Press Release
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`E] FDA Talk Paper
`0
`Indicate what types (if any) of information dissemination are anticipated
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`[I CDER Q&As
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`D Other
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`3 Answer all questions in all sections in relation to the pending application, i.e., if the pending application is an NDA or BLA
`supplement, then the questions should be answered in relation to that supplement, not in relation to the original NDA or BLA. For
`example, if the application is a pending BLA supplement, then a new RMS-BLA Product Information Sheetjbr 731’ must be
`completed.
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`Version:
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`l2/09/2013
`
`

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`BLA #125390
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`Page 3
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`Is approval of this application blocked by any type of exclusivity?
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`o NDAs and BLAs: Is there existing orphan drug exclusivity for the “same”
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`drug or biologic for the proposed indication(s)? Refer to 21 CFR
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`If, yes, NDA/BLA #
`and
`31 6.3(b)(13) for the definition of “same drug "for an orphan drug (i.e.,
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`active moiety