CENTER FOR DRUG EVALUATION AND
`
`RESEARCH
`
`APPLICA TION NUMBER:
`
`21-372/S008/S010
`
`ADMINISTRATIVE and CORRESPONDENCE
`
`DOCUMENTS
`
`

`

`EXCLUSIVITY SUMMARY
`
`NDA # 21-372
`
`SUPPL # S-008/
`
`('0) (4)
`
`HFD # 180
`
`Trade Name Aloxi
`
`Generic Name Palonosetron Hydrochloride
`
`Applicant Name Helsinn Healthcare SA
`
`Approval Date, If Known N/A
`
`PART I
`
`IS AN EXCLUSIVITY DETERMINATION NEEDED?
`
`1. An exclusivity determination will be made for all original applications, and all efficacy
`supplements. Complete PARTS II and III of this Exclusivity Summary only if you answer "yes" to
`one or more of the following questions about the submission.
`
`a) Is it a 505(b)(l), 505(b)(2) or efficacy supplement?
`
`YES E
`
`NO [1
`
`Ifyes, what type? Specify 505(b)(1), 505(b)(2), SE1, SE2, SE3,SE4, SE5, SE6, SE7, SE8
`
`8-008 (SE1)
`
`- both are 505(b)(1)
`
`('0) (4)
`
`c) Did it require the review of clinical data other than to support a safety claim or change in
`labeling related to safety? (If it required review only of bioavailability or bioequivalence
`data, answer "no."
`
`YES
`
`NO El
`
`If your answer is "no" because you believe-the study is a bioavailability study and, therefore,
`not eligible for exclusivity, EXPLAIN why it is a bioavailability study, including your
`reasons for disagreeing with any arguments made by the applicant that the study was not
`simply a bioavailability study.
`
`N/A
`
`If it is a supplement requiring the review of clinical data but it is not an effectiveness
`supplement, describe the change or claim that is supported by the clinical data:
`
`N/A
`
`Page 1
`
`(b) (4)
`
`(b) (4)
`
`

`

`(1) Did the applicant request exclusivity?
`
`YES
`
`NO 1:]
`
`If the answer to (d) is "yes," how many years of exclusivity did the applicant request?
`
`3 years
`
`e) Has pediatric exclusivity been granted for this Active Moiety?
`YES [3
`
`NO IE
`
`If the answer to the above question in YES, is this approval a result of the studies submitted in
`response to the Pediatric Written Request?
`'
`
`IF YOU HAVE ANSWERED "NO" TO ALL OF THE ABOVE QUESTIONS, GO DIRECTLY TO
`THE SIGNATURE BLOCKS AT THE END OF THIS DOCUMENT.
`
`2. Is this drug product or indication a DESI upgrade?
`
`YESIj
`
`N0|E
`
`IF THE ANSWER TO QUESTION 2 IS "YES," GO DIRECTLY TO THE SIGNATURE BLOCKS
`ON PAGE 8 (even if a study was required for the upgrade).
`
`PART II
`
`FIVE-YEAR EXCLUSIVITY FOR NEW CHEMICAL ENTITIES
`
`(Answer either #1 or #2 as appropriate)
`
`1. Single active ingredient product.
`
`Has FDA previously approved under section 505 of the Act any drug product containing the same
`active moiety as the drug under consideration? Answer "yes" if the active moiety (including other
`esterified forms, salts, complexes, chelates or clathrates) has been previously approved, but this
`particular form ofthe active moiety, e.g., this particular ester or salt (including salts with hydrogen or
`coordination bonding) or other non-covalent derivative (such as a complex, chelate, or clathrate) has
`not been approved. Answer "no" if the compound requires metabolic conversion (other than
`deesterification of an esterified form of the drug) to produce an already approved active moiety.
`
`YES g
`
`NO |:|
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(S).
`
`Page 2
`
`

`

`NDA#
`
`21-372
`
`Aloxi (palonosetron hydrochloride) 0.25 mg I.V.
`
`NDA#
`
`NDA#
`
`2. Combination product.
`
`.
`
`If the product contains more than one active moiety(as defined in Part II, #1), has FDA previously
`approved an application under section 505 containing a_ny Qfl of the active moieties in the drug
`product? If, for example, the combination contains one never-before-approved active moiety and
`one previously approved active moiety, answer "yes." (An active moiety that is marketed under an
`OTC monograph, but that was never approved under an NDA,
`is considered not previously
`a
`roved.
`pp
`)
`YES E]
`NO
`
`If "yes," identify the approved drug product(s) containing the active moiety, and, ifknown, the NDA
`#(s).
`*
`
`NDA#
`
`NDA#
`
`NDA#
`
`IF THE ANSWER TO QUESTION 1 OR 2 UNDER PART 11 IS "NO," GO DIRECTLY TO THE
`SIGNATURE BLOCKS ON PAGE 8. (Caution: The questions in part II of the summary should
`only be answered “NO” for original approvals of new molecular entities.)
`IF “YES,” GO TO PART III.
`
`PART III
`
`THREE-YEAR EXCLUSIVITY FOR NDAs AND SUPPLEMENTS
`
`To qualify for three years of exclusivity, an application or supplement must contain "reports of new
`clinical investigations (other than bioavailability studies) essential to the approval ofthe application
`and conducted or Sponsored by the applicant." This section should be completed only ifthe answer
`to PART 11, Question 1 or 2 was "yes."
`
`1. Does the application contain reports of clinical investigations? (The Agency interprets "clinical
`investigations" to mean investigations conducted on humans other than bioavailability studies.) If
`the application contains clinical investigations only by virtue of a right of reference to clinical
`investigations in another application, answer "yes," then skip to question 3(a). Ifthe answer to 3(a)
`is "yes" for any investigation referred to in another application, do not complete remainder of
`
`Page 3
`
`

`

`summary for that investigation.
`
`YES g NO [I
`
`IF "NO," GO DIRECTLY TO THE SIGNATURE BLOCKS ON PAGE 8.
`
`2. A clinical investigation is "essential to the approval" if the Agency could not have approved the
`application or supplement without relying on that investigation. Thus, the investigation is not
`essential to the approval if 1) no clinical investigation is necessary to support the supplement or
`application in light of previously approved applications (i.e., information other than clinical trials,
`such as bioavailability data, would be sufficient to provide a basis for approval as an ANDA or
`505(b)(2) application because of what is already known about a previously approved product), or 2)
`there are published reports of studies (other than those conducted or sponsored by the applicant) or
`other publicly available data that independently would have been sufficient to support approval of
`the application, without reference to the clinical investigation submitted in the application.
`
`(a) In light of previously approved applications, is a clinical investigation (either conducted
`by the applicant or available from some other source, including the published literature)
`necessary to support approVal of the application or supplement?
`YES X
`
`NO D
`
`If "no," state the basis for your conclusion that a clinical trial is not necessary for approval
`AND GO DIRECTLY TO SIGNATURE BLOCK ON PAGE 8:
`
`(b) Did the applicant submit a list of published studies relevant to the safety and effectiveness
`ofthis drug product and a statement that the publicly available data would not independently
`support approval of the application?
`'
`
`YES [I
`
`NO E
`
`(1) If the answer to 2(b) is "yes," do you personally know of any reason to disagree
`with the applicant's conclusion? If not applicable, answer NO.
`
`YES |:]
`
`NO D
`
`If yes, explain:
`
`(2) Ifthe answer to 2(b) is "no," are you aware of published studies not conducted or
`sponsored by the applicant or other publicly available data that could independently
`demonstrate the safety and effectiveness of this drug product?
`
`YES I:
`
`No
`
`Page 4
`
`

`

`If yes, explain:
`
`(0)
`
`Ifthe answers to (b)(1) and (b)(2) were both "no," identify the clinical investigations
`submitted in the application that are essential to the approval:
`('0) (4)-
`
`8-008,
`
`Investigation #1: PALO-04-06 (Phase 3 trial - pivitol investigation)
`Investigation #2: PALO-04—O7 (Phase3 trial - confirmatory study)
`Study 2500 (Phase 2 trial confirmatory study)
`
`Studies comparing two products with the same ingredient(s) are considered to be bioavailability
`studies for the purpose of this section.
`
`3. In addition to being essential, investigations must be "new" to support exclusivity. The agency
`interprets "new clinical investigation" to mean an investigation that 1) has not been relied on by the
`agency to demonstrate the effectiveness of a previously approved drug for any indication and 2) does
`not duplicate the results ofanother investigation that was relied on by the agency to demonstrate the
`effectiveness of a previously approved drug product, i.e., does not redemonstrate something the
`agency considers to have been demonstrated in an already approved application.
`
`a) For each investigation identified as "essential to the approval," has the investigation been
`relied on by the agency to demonstrate the effectiveness of a previously approved drug
`produCt?
`(If the investigation was relied on only to support the safety of a previously
`approved drug, answer "no.")
`
`Investigation #1
`
`Investigation #2
`
`YES El
`
`NO
`
`YES [3
`
`NO g
`
`If you have answered "yes" for one or more investigations, identify each such investigation
`and the NDA in which each was relied upon:
`
`b) For each investigation identified as "essential to the approval", does the investigation
`duplicate the results of another investigation that was relied on by the agency to support the
`effectiveness of a previously approved drug product?
`
`Investigation #1
`
`Investigation #2
`
`YES El
`
`NO IE
`
`YES E]
`
`NO XI
`
`Page 5
`
`(b) (4)
`
`

`

`If you have answered "yes" for one or more investigation, identify the NDA in which a
`similar investigation was relied on:
`
`c) If the answers to 3(a) and 3(b) are no, identify each "new" investigation in the application
`or supplement that is essential to the approval (i.e., the investigations listed in #2(c), less any
`that are not "new" :
`
`(b) (4)
`
`8-008)
`
`Investigation #1: PALO-04-06 (Phase 3 trial - pivitol investigation)
`Investigation #2: PALO-O4—07 (Phase3 trial - confirmatory study)
`Study 2500 (Phase 2 trial confirmatory study
`
`4. To be eligible for exclusivity, a new investigation that is essential to approval must also have
`been conducted or sponsored by the applicant. An investigation was "conducted or sponsored by"
`the applicant if, before or during the conduct ofthe investigation, 1) the applicant was the sponsor of
`the IND named in the form FDA 1571 filed with the Agency, or 2) the applicant (or its predecessor
`in interest) provided substantial support for the study. Ordinarily, substantial support will mean
`providing 50 percent or more of the cost of the study.
`
`a) For each investigation identified in response to question 3(0): if the investigation was
`carried out under an IND, was the applicant identified on the FDA 1571 as the sponsor?
`
`.
`
`!1
`
`2 NO |:|
`! Explain:
`
`!2
`
`1 NO El
`! Explain:
`
`Investigation #1
`
`IND#39,797
`
`YES
`
`Investigation #2
`
`IND#39,797
`
`YES
`
`(b) For each investigation not carried out under an IND or for which the applicant was not
`identified as the sponsor, did the applicant certify that it or the applicant's predecessor in
`
`Page 6
`
`(b) (4)
`
`

`

`interest provided substantial support for the study?
`
`Investigation #1
`
`YESI:I
`Explain:
`
`lv
`
`!NOI:I
`! Explain:
`
`Investigation #2
`
`!
`
`YESD
`Explain:
`
`!NO|:I
`! Explain:
`
`(0) Notwithstanding an answer of "yes" to (a) or (b), are there other reasons to believe that
`the applicant should not be credited with having "conducted or sponsored" the study?
`(Purchased studies may not be used as the basis for exclusivity. However, if all rights to the
`drug are purchased (not just studies on the drug), the applicant may be considered to have
`sponsored or conducted the studies Sponsored or conducted by its predecessor in interest.)
`
`YEslj
`
`NOIZ
`
`If yes, explain:
`
`Name of person completing form: Jagjit Grewal
`Title: Regulatory Project Manager
`»
`Date: 2/26/08
`
`Name of Office/Division Director signing form: Joyce Korvick
`Title: Deputy Division Director
`
`Page 7
`
`

`

`Form OGD-011347; Revised 05/10/2004; formatted 2/15/05
`
`Page 8
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Jagjit S Grewal
`2/29/2008 06:37:42 PM
`CSO
`
`Joyce Korvick
`2/29/2008 07:38:22 PM
`MEDICAL OFFICER
`
`

`

`Pediatric Research and Equity Act Deferrals
`
`Product name and active ingredient/ dosage form: Aloxi gpalonosetron hydrochloride2
`Intravenous Injection, 0.075 mg/ 1.5 mL
`b
`4
`
`NDA #: NDA 21-372
`
`)
`) (
`(
`Supplement Type: SEl— new indication (8008,
`SE8— labeling w/clinical change (S0102
`
`Supplement Numbers: 8-008,
`
`8-010
`
`HFD-1—80
`
`Indication(s): Two new indications
`(NOTE: If the drug is approved for or you are seeking approval for more than one
`indication, address the following for each indication.)
`
`o
`
`Indication #1 (8-0082: Aloxi18 indicated for the prevention of post operative nausea
`and vomiting (PONV2 for up to
`(b) (4)
`
`1. Deferral specifics
`a. Pediatric age group(s) included in deferral:
`
`1 month to 16 years old
`
`b. Reason(s) for requesting deferral of pediatric studies (address each age group
`separately and for each age group — choose all that apply):
`Adult studies completed and ready for approval
`El Additional safety or effectiveness data needed (describe)
`El Other (specify)
`
`0. Pediatric age group(s) not included in deferral: 0 months to 1 month old
`
`(1. Reason(s) for not including the pediatric age group(s) listed in letter c in the
`deferral request (address each excluded age group separately and for each such
`age group —— choose all that apply):
`El Adequate pediatric labeling exists
`El Studies completed in the specified age group ‘
`Requesting a partial waiver
`El Other (specify)
`
`2. The law requires that certain criteria be met BEFORE a deferral is granted.
`the applicant must submit——
`“(1) certification of the grounds for deferring the assessments;
`“(11) a description of the planned or ongoing studies;
`“(111) evidence that the studies are being conducted or will be conducted with due
`diligence and at the earliest possible time; and
`“(IV) a timeline for the completion of such studies.
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`Has the Sponsor submitted these (if yes, this should be reviewed at the same time
`as the deferral).
`Yes, pediatric plan submission dated November 2, 2007
`
`3. Has a pediatric plan been submitted to the Agency? Note: Pediatric plans MUST
`be reviewed by the Pediatric Review Committee (PeRC)
`
`o
`
`o
`
`If so, provide date
`
`Submission dated November 2 2007
`
`If not, provided projected date pediatric plan is to be submitted
`
`3. Timeline for the completion of studies
`December 13 2008
`
`4. Has a Written Request been issued?
`
`M
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`(b) (4)
`
`

`

`
`
`(b) (4)
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Jagj it 8 Grewal
`2/26/2008 11:38:12 AM
`CSO
`
`

`

`
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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.
`
`Iris Masucci
`
`2/21/2008 09:56:52 AM
`DDMAC REVIEWER
`
`Laurie Burke
`
`2/25/2008 11:54:28 AM
`INTERDISCIPLINARY
`
`

`

`MEMORANDUM OF TELECON
`
`DATE: February 13, 2008, 1:00PM EST
`
`APPLICATION NUMBER: NDA 21-372/5-008, (b) W's-010
`
`BETWEEN:
`
`Name:
`
`Craig Lehmann, Pharm.D., US Agent (August Consulting)
`Dr. Dario Ceriani, Deputy Director, Regulatory Affairs, Helsinn
`Dr. Mauro Capodiferro, Manager, Corporate Regulatory Affairs, Helsinn
`Dr. Giuseppina Clerici, Manager Corporate Clinical Development, Helsinn
`
`(304) 345—7563
`Phone:
`Representing: Helsinn Healthcare SA
`
`AND
`
`Name:
`
`Dr. Hugo Gallo-Torres, Medical Team Leader
`Dr. Nancy Snow, Medical Officer
`Jagjit Grewal, RPM
`
`Division of Gastroenterology Products, HFD-l 80
`
`SUBJECT: Inform Sponsor of PeRC Committee Recommendations of Pediatric Plan
`
`Helsinn Healthcare SA submitted their pediatric drug development plan dated November 2, 2007
`in response to the FDA letter dated July 2, 2007. The sponsor’s pediatric plan was reviewed
`earlier today by the Agency’s PeRC Review Committee. This teleconference was to convey the
`PeRC committee’s recommendations regarding the sponsor’s pediatric plan.
`
`1. The sponsor was informed that they should submit publications/data to justify their request
`for partial waiver in the 0 to 1 month of age population. The sponsor agreed to submit
`publications/data to support the requested waiver for 0 to 1 month of age.
`
`2. The sponsor was also informed that they should incorporate a PK study in their pediatric plan
`to determine appropriate dosing. The sponsor indicated that the inclusion of a PK study with
`the pediatric plan was discussed in at the pre-sNDA meeting December 7, 2006 at which
`several FDA Pediatric Staff attended. During the pre-sNDA meeting, it was noted that for
`the very low I.V. palonosetron doses planned for the pediatric assessment study in pediatric
`patients (1 meg/kg and 3 meg/kg), the plasma levels are very low and largely below the limit
`of quantitation for the analytical method. Only the Cmax and several hours of plasma
`concentrations after the Cmax are expected to be captured in a PK analysis for the lowest dose
`(1 mcg/kg) and limited characterization for the 3 meg/kg dose.
`
`(b) (4)
`
`

`

`It was noted that at the pre-sNDA meeting, Dr. Lisa Mathis (PMHS) expressed concern that it
`would not be appropriate to stick children under these circumstances since useful PK data would
`not be obtained, and therefore it was suggested that the Sponsor perform modeling of the PK
`parameters for these low PON\
`(b) (4):loses instead of performing an in-Vivo pediatric PK trial.
`The Sponsor agreed to perform the modeling instead of a pediatric PK study at the pre-sNDA
`meeting.
`
`Dr. Gallo-Torres commented that he thinks this is a reasonable approach, that by itself the Cmax is
`not expected to be usefiil without the additional PK parameters, and that the Sponsor should
`provide this explanation in a reply submission.
`
`The sponsor expects to submit the requested information (justification of requested partial waiver
`and explanation of the basis for modeling of the PK parameters) within one week of today’s
`teleconference.
`
`
`
`J agj it Grewal, MPH
`Regulatory Project Manager
`
`(b) (4)
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Jagj it S Grewal
`2/19/2008 02:24:50 PM
`CSO
`
`

`

`r
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`
`Office ofDrug Evaluation ODE III
`
`
`
`FACSIMILE TRANSMITTAL SHEET
`
`
`DATE: February 28, 2008
`
`Craig Lehmann
`To: US Agent for Helsinn Healthcare SA
`
`Jagi it Grewal, MPH
`rom: Regulatory Project Manager
`
`Company: August Consulting
`
`'
`
`Division of Gastroenterology Products
`
`Fax number: (512) 347-9375
`
`Fax number: (301) 796-9905
`
`Phone number: (512) 347-1755
`
`Phone number: (301) 796-0846
`
`
`
`Subject: NDA 21-372/8-008/8-010 (Aloxi I.V.) — Additional Labeling Comments
`
`3
`Total No. of pgs
`including cover:
`
`
`
`
`DOCUMENT TO BE MAILED? NO
`
`Dr. Lehmann,
`
`Please find enclosed additional labeling comments in regards to NDA 21—3 72/S-008/S-010 for Aloxi (palonosetron
`hydrochloride) 0.075 mg/1.5 mL intravenous injection.
`1 can be reached through the above contact information or
`email if you have any questions. Thank you.
`
`Jagjit Grewal
`Regulatory Project Manager
`Division of Gastroenterology Products
`Food & Drug Administration
`
`THIS DOCUMENT IS INTENDED ONLY FOR THE USE OF THE PARTY T0 WHOM IT IS ADDRESSED AND MAY CONTAIN
`INFORMATION THAT IS PRIVILEGED, CONFIDENTIAL, AND PROTECTED FROM DISCLOSURE UNDER APPLICABLE LAW.
`
`If you are not the addressee, or a person authorized to deliver this document to the addressee, you are hereby notified that any review, disclosure,
`dissemination, copying, or other action based on the content of this communication is not authorized. If you have received this document in error,
`please notify us immediately by telephone at (301) 796-2120. Thank you.
`
`

`

`NDA 21-372/S-008/S-010
`
`Page 2
`
`Please refer to your April 27, 2007 supplemental new drug applications submitted under
`section 505(b) of the Federal Food, Drug, and Cosmetic Act for Aloxi (palonosetron
`hydrochloride) 0.075 mg/l .5 mL intravenous injection.
`
`We are reviewing the proposed labeling of your submission and have the following
`comments.
`
`A. Container Label
`
`1. Revise the established name and product strength so that is in accordance
`(b) (4) Consult Rik Lostritto, chair of the
`CDER Labeling and Nomenclature Committee for further guidance.
`
`Revise the color scheme for the 0.075 mg/1.5 mL strength to ensure it is
`adequately differentiated from the 0.25 mg/5 mL strength.
`
`. Revise the color scheme for the proprietary name so that the entire name is
`presented in one color font.
`
`Revise the color of the font utilized for the established name and product
`strength so that it provides adequate contrast against the grey backround.
`
`.
`
`Increase the prominence of the established name and product strength.
`
`B. Carton Labeling
`l. Revise the established name and product strength so that is in accordance
`(b) (4) Consult Rik Lostritto, chair of the
`CDER Labeling and Nomenclature Committee for further guidance.
`
`Revise the color scheme of the proprietary name so that the entire name is
`presented in one color font.
`
`. Revise the color of the font utilized or the established name and product
`strength so that it provides adequate contrast against the grey backround.
`
`Increase the prominence of the established name and product strength.
`
`. Eliminate the use of trailing zeroes.
`
`Include a “New Strength” banner on the principal display panel for a period
`not to exceed six months.
`
`(b) (4)
`
`(b) (4)
`
`

`

`NDA 21-372/8—008/8-010
`
`Page 3
`
`C. Package Insert Labeling
`
`1. HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`USE IN SPECIFIC POPULATIONS — referecnce “(8.4)” at the end of the
`sentence, “Safety and effectiveness in patients below the age of l 8 years
`have not been established (8.4)”
`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`DOSAGE AND ADMINISTRATION — put a space between the words
`“administered” and “over” under the PONV subsection.
`
`. HIGHLIGHTS OF PRESCRIBING INFORMATION
`
`“See 17 for PATIENT COUSELING INFORMATION and FDA-aproved
`patient labeling.” The words “Patient” and “Labeling” should be
`capitalized.
`
`FULL PRESCRIBING INFORMATION
`
`Section 6 ADVERSE REACTIONS — delete the subsection heading
`Delete the space between the heading
`“ADVERSE REACTIONS” and the first paragraph beginning “Because
`clinical trials are conducted under widely varying conditions...”
`
`. FULL PRESCRIBING INFORMATION
`
`Section 6.1 & 6.2 — the subheadings “CHEMOTHETAPY-INDUCED
`NAUSEA AND VOMITING” and “POSTOPERATIVE NAUSEA AND
`
`VOMITING” should not be written in all caps. The headings should be
`listed as “Chemotherapy-Induced Nausea and Vomiting” and “Postoperative
`Nausea and Vomiting.” Do not underline these two subheadings.
`
`FULL PRESCRIBING INFORMATION
`
`Section 14.1 & 14.2 — the subheadings “CHEMOTHETAPY—INDUCED
`NAUSEA AND VOMITING” and “POSTOPERATIVE NAUSEA AND
`
`VOMITING” should not be written in all caps. The headings should be
`listed as “Chemotherapy-Induced Nausea and Vomiting” and “Postoperative
`Nausea and Vomiting.” Do not underline these two subheadings.
`
`FULL PRESCRIBING INFORMATION
`
`Section 14.1 Chemotherapy-Induced Nausea and Vomiting — referring to the
`first paragraph after Table 5, correct the spelling of the word “the.”
`
`(b) (4)
`
`

`

`
`
`02Q’28/2008 11:55 FAX
`
`3014433285 7
`
`DBP
`
`'
`
`
`
`I001
`
`
`
`TRANSMISSION UK
`
`TX/RX N0
`RECIPIENT ADDRESS
`DESTINATION ID
`
`ST. TIME
`TIME USE
`PREES SENT
`RESULT
`
`‘
`
`***********X*XX*****X
`***
`TX REPORT
`***
`****xx****xxxxxxxxx*x
`
`'
`
`.
`
`2873
`815123478375
`
`02/28 11 55
`00'34
`3
`
`UK
`
`r
`
`Food and Drug Administration
`Center for Drug Evaluation and Research
`
`Office ofDrugEvaluation ODE III
`
`
`FACSIMILE TRANSMITTAL SHEET1
`
`DATE: February '28. 2008
`Craig Lchmann
`To: US Agent for'Hclninn Healthcare SA
`
`
`Jagjit Grewal, MPH
`I rom: Regulatory Project Manager
`
`'
`
`'
`
`Company: August Consulting
`
`Fax number: (512) 347-9375
`
`
`Division of Gastrocntcrology Products
`Fax number: (301) 796-9905
`
`Phone number: (512) 347—1755
`
`_
`
`Phone number: (301)796-0846
`
`Subject:
`NDA 21—372/3—003/s-010 (Aloxi I.V.) _ Additional Labeling Comments
`
`m
`‘
`
`3
`Total No. of pgs
`including cover:
`
`WmM
`
`
`
`
`
`DOCUMENT TO BE MAILED? N0
`Dr, Lehmann,
`'
`
`'
`
`Please find enclosed additional labeling comments in regards to NDA 21-372/8-008/8-010 for Aloxi (palomsetron
`hydrochloride) 0.075 rug/1.5 mL intravenous injection. I can be reached through the ab0ve contact information or
`V email if you have any questions. Thank you.
`
`Jagi it Grown]
`Regulatory Project Manager
`Division of Gastroentcrology Products
`Food & Drug Administration
`
`_
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Jagjit S Grewal
`2/28/2008 11:06:20 AM
`CSO
`
`

`

`Page 1 of 1
`
`Grewal, Jagjit
`
`From:
`
`Sent:
`
`To:
`
`Grewal, Jagjit
`
`Friday, February 22, 2008 4:45 PM
`
`'Lehmann, Craig‘
`
`(b)
`Grewal, Jagjit
`Cc:
`(4)8010 - FDA Revised Label 2/22/08
`NDA 21-372/SOOBI
`Subject:
`Attachments: Aloxi |.V. — FDA Revised Label 2.22.08.doc
`
`Hello Craig,
`
`Please find attached the Agency's revised label in response to the sponsor revised label dated 2/19/08.
`Additionally, I did received your email earlier today indicating the submission of a 4 month safety update,
`statement of good clinical practices, and revised AE Table 2 for labeling. Thank you.
`
`Jagj it Grewal, MPH
`Regulatory Project Manager
`Division of Gastroenterology Products
`CDER/OND/ODE 111
`
`Food & Drug Administration
`
`Phone: (301) 796-0846
`Fax:
`(301) 796-9905
`Email: Jagjit. Grewal@fda. hhs. gov
`
`2/27/2008
`
`(b)
`(4)
`
`

`

`fil’agds) Withheld
`
`§ 552(b)(4~) Trade Secret / Confidential
`
`
`
`/ § 552(b)(4) Draft Labeling
`
`§ 552(b)(5) Deliberative Process
`
`Withheld Track Number: Administrative- 02"} 75‘
`soccefl/fl
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Jagjit S Grewal
`2/27/2008 11:11:37 AM
`CSO
`
`

`

`Page I of 1
`
` Grewal, Jagjit
`
`From:
`
`Sent:
`
`To:
`
`Grewal, Jagjit
`
`Thursday, February 14, 2008 5:45 PM
`
`'Lehmann, Craig‘
`
`Grewal, Jagjit
`Cc:
`NDA 21-372/8008(b) (4)8010 FDA Revised Labeling
`Subject:
`Attachments: FDA Revised Label 2.14.08.doc
`
`Hello Craig,
`
`(D) (4)
`
`Please find attached the FDA's proposed changes to the labeling for NDA 21-372/8008
`Please review and feel free to contact me with any questions.
`
`SO10 Aloxi lV.
`
`l will fonlvard marked up carton and vial labeling once I received feedback from our reviewers. Thank you.
`
`Jagjit Grewal, MPH
`Regulatory Project Manager
`Division of Gastroenterology Products
`CDER/OND/ODE III
`
`Food & Drug Administration
`
`(301) 796—0846
`Phone:
`(301) 796-9905
`Fax:
`Email: Jagjit. Grewal@fda. hhs.gov
`
`2/27/2008
`
`(b) (4)
`
`(b) (4)
`
`

`

`#Pagds) Withheld
`
`§ 552(b)(4) Trade Secret / Confidential
`
`# § 552(b)(4) Draft Labeling
`
`§ 552(b)(5) Deliberative Process
`
`Withheld Track Number: Administrative-QI’ 3 ‘7;
`5099/50/&
`
`

`

`This is a representation of an electronic record that was signed electronically and
`this page is the manifestation of the electronic signature.
`
`Jagj it S Grewal
`2/27/2008 11:05:46 AM
`CSO
`
`

`

`_
`
`Public Health SerVIce
`
`.
`
`Food and Drug Administration
`Rockville, MD 20857
`
`DEPARTMENT OF HEALTH & HUMAN SERVICES
`
`1 /
`
`ab
`
`NDA21-372/S-008,
`
`(b)
`(4)310
`
`Helsinn Healthcare
`
`Attn: Craig Lehmann
`Authorized US Agent
`c/o August Consulting , Inc
`515 Capital of Texas Highway, Suite 150
`Austin, Texas 78746
`
`Dear Dr. Lehmann:
`
`Please refer to your supplemental new drug application submitted under section 505(b) of the
`Federal Food, Drug, and Cosmetic Act for Aloxi® (palonosetron) Injection, 0.025mg/5mL.
`
`We also refer to your submission dated July 27, 2007 asking for additional clarification
`regarding the electronic data sets being requested in the July 2, 2007 filing letter.
`
`We are reviewing the statistical section of your submission and have the following comments
`and information requests. We request a prompt written response in order to continue our
`evaluation of your supplemental application.
`
`The list below attempts to clarify our original requests as well as request additional information
`and data variables.
`
`Part 1. Response to specific questions in your July 27, 2007 submission
`
`Response to Specific Question #1
`
`For each of the two Studies (PALO-04—O6 and PALO-04-07), please provide a single data set
`for the requested variables/information in a horizontal structure (i.e., one record per patient
`where each parameter for a given time interval becomes a single variable). This data set is
`further clarified. We are asking only for two analysis data sets, one per study, which we will
`analyze. It is not necessary for you to modify your original programs to reproduce hand-
`tabulated in-text tables. Please submit whatever SAS programs (source code listings) you
`have used to generate the tables or input for the tables.
`
`(b)
`(4)
`
`

`

`NDA 21—372/S—08. E43010
`
`b
`
`Page 2
`
`Response to Specific Question #2
`
`Please add to the two data sets (described in “Response to Specific Question#1”) the
`additional time intervals (2 to 6 hours, 6 to 48 hours, and 6 to 72 hours) needed to generate
`the requested tables. (Part III of this correspondence shows the listing of variables to be
`included in the requested data sets.)
`
`Response to Specific Question #3
`
`For Study PALO-04-06, please provide your SAS programs which used the FAS population
`to generate Tables 12 to 21, and 23 while for Study PALO-04-07, please provide SAS
`programs which used the PFAS population to generate Tables 13, 14, 19, 20, 21, 22, 23, 24,
`25, and 27.
`‘
`
`In order to facilitate the review process, as requested in item #2 of FDA’s filing letter dated
`July 2, 2007, for each of the two requested data, please add any additional variables that were
`needed to generate the requested tables.
`
`As stated for #1, it is not necessary for you to modify your original programs so as to
`reproduce hand-tabulated in—text tables or to generate new tables from the new data sets.
`Please submit whatever SAS programs (source code listings) you have used to generate the
`tables or input for the tables.
`
`Response to Specific Question #4
`
`Please provide SAS programs to generate Table 21 for Study PALO-04-06 and Table 25 for
`Study PALO-04-07. You do not need to provide data for the severity of nausea.
`
`Response to Specific Question #5
`
`We are not requesting data for rescue medication nor the SAS programsused to analyze it.
`
`Response to Specific Question #6
`
`Please provide the SAS programs used to calculate the correlation between nausea and
`vomiting and the SAS analysis programs used for the Quality of Life assessments presented
`in Tables 3.12.1.1 to 3.12.1.6 in section 16.5 for Study PALO-04-06. The Quality of Life
`data are not being requested.
`
`No data and no programs are being requested for Quality of Life for Study PALO—04-O7.
`
`Additional comments: If further clarification is still needed regarding this communication, we
`recommend you request a TCON.
`
`(b)
`(4)
`
`

`

`('0)
`NBA 21-372/S-OE (4)010
`Page 3
`
`Part II. Additional information request
`
`1.
`
`(b) (4)
`
`2. Please add a new variable to the requested data set for Study PALO-04-07 as an indicator
`for potential un-blinding:"yes’for a patient involved1n the un-blindinglssue; or‘‘”no
`for a patient not involved. (Part III