Form Approved · OMB No 091[).()001 ExpiraUon Date· December 31 2011· see PRA Statement on last page
`DEPARTMENT OF HEALTH AND HUMAN SERVICES 1. Date Submitted
`3. NDAIANDAIAADA or BLAIPMA
`Type: D
`Number: 202236
`Food and Drug Administration
`06116/2015
`0 Multiple products
`~ Single product
`TRANSMIIT AL OF ADVERTISEMENTS
`For multiple products, submit completed fom1 and
`AND PROMOTIONAL LABELING FOR
`specimen of advertising/promotional materials to
`DRUGS AND BIOLOGICS
`one application of choice, and attach separate
`sheet addressing items 3-5 for remainder of
`FOR HUMAN USE
`products. Refer to No. 3 on instruction sheet.
`
`2. Label Review Number
`(Biologics)
`
`NOTE: Fonn FDA 2253 is required by law. Reports are required for approved NDAs and ANDAs (21 CFR 314.81).
`4. Proprietary Name
`5. Established Name
`azelastine hydrochloride and fluticasone propionate
`
`DYMI TA
`
`6. Package Insert Date and ID Number
`(Latest final printed labeling)
`
`rN-023A6-05
`
`02/2015
`
`Product Code No.:
`7. Manufacturer Name
`MEDA Pharmaceuticals lnc.
`
`License No. (Biologics):
`
`8.
`
`a. Please cheek only one:
`
`Advertisement I Promotional Labeling Materials
`0 Consumer
`18) Professtonal
`
`Material Type
`(use FDA codes)
`
`b.
`
`Sales Aid
`
`Dlssemtnatlon/
`Publication
`Date
`c.
`07/06/2015
`
`Material 10 Code
`
`d.
`US/DYM/041 :5/005-1
`
`201· Fall CV
`
`Material Description
`
`e.
`
`Sales
`
`id
`
`07/06/2015
`
`US/DYM/0415/005-Ia( I) 2015 Fall CVA New Indication Violator
`
`Delete
`Row
`
`Delete
`Row
`
`f. Comments
`
`To delete a row, click the "Delete Row" button for that row (or press the enter key
`
`if you 've tabbed Into the button}. You cannot delete the last remaining row.l Add New Row I
`
`NOTE: U /DYM/0415/0054a( I). 20 15 Fall CV A Ne\ Indication Violator to be used for 6 months only.
`
`9. Applicant's (or Agent's) Return Address
`Address 1 (Street address. P.O. box, company name c/o)
`Meda Pharmaceuticals Inc.
`
`Address 2 (Apartment. swte, unit, building, floor, etc.}
`265 Davidson venue
`
`City
`omerset
`
`Country
`
`U A
`
`I State/Province/Region
`I ZIP or Postal Code
`
`ew Jersey
`
`08873-4120
`
`-IP'
`
`10. Responsible Official's (or Agent's)
`a. Telephone Number (Include area code}
`
`732-56+-2284
`
`b. FAX Number (Include area code)
`
`732-56+-2377
`
`c. Email Address
`
`lorna-jane.breme ~meda. us
`
`FORM FDA 2253 (12/14) PREVIOUS EDITION IS OBSOLETE
`
`Page 1 of 2
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`PTX0916
`
`MEDA_APTX0347 4429
`
`PLAINTIFFS'
`TRIAL EXHIBIT
`
`PTX0916-00001
`
`1
`
`CIP2084
`Argentum Pharmaceuticals LLC v. Cipla Ltd.
`IPR2017-00807
`
`

`

`11 . Typed Name and Tille of Responsible Official or Agent 12. Signature of Responsible Official or Agent
`
`13. Date
`
`Lorna-Jane Bremer, enior Director Regulatory
`Affair
`
`14. For CBER Products Only (Check one)
`
`0 Draft
`
`{./
`0 Final
`
`(
`
`I Sign I 0611 6/2015
`
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`*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.*
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`
`FORM FDA 2263 (12/14) PREVIOUS EDITION IS OBSOLETE
`
`Page 2 of 2
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`MEDA_APTX03474430
`
`PTX0916-00002
`
`2
`
`

`

`DYMISTA~
`(azelasline hydrochloride and
`fluticasone propionate) Nasal Spray
`137mcg/50 meg per Spray
`POLLEN MISERY DEFLECTED
`
`For seasonal allergic rhinitis (SAR) sufferers 6 and older
`""""~"'~-
`
`DON'T LET
`POLlEN
`.. • 4!.
`GET
`THE
`BETTER
`OF YOUR
`PATIENTS
`
`Only Oymista offers fast reliefa and inflammation control-with every dose1· 2
`As demOilSfr,tle<l 111 paoerus 12 1rd Older as! re el del ned as me IllS! hmepoon1 (30 mlllllles) al whdl DymiStl "' s s.gr ilicantl SUPenor to pl.1cebo rn lhe
`mea~ chall!r. ' om b.l
`ne " rnsl 1 :taneous 10 I nasal symploJm score ! rTNSSI and was sust.1 ned thcJealter
`
`Indications
`DYMISTA con atns an Hl·receptor antagomst and a corttcosterotd and tS tndtcated for the relief of
`symptoms of seasonal allergic rhtnttts tn patten s 5 years of age ana older who reqUtre treatment wtth both
`azelasttne hydrochlorrde and ftutrcasone proptonate or symptomatic reltel
`Important Safety Information
`• Somnolencr Avotd engagmg tn hazardous occupattons requtnng complete mental a!er ness such as
`dnvrng or operattng machtner wnen taKtng DYMISTA
`• Avord concurrent use of alcohol oro her central nervous system <CNS) depressants wrth DYMISTA
`because urther decreased alertness and tmpatrment of CNS performance may occur
`• Eptstaxts. nasal ulcera tons. nasal septal perforatron. tmpatred wouncl healtng. Candida albrcans tnfectton
`Mont tor pa tents oenodrcally for stgns of adverse effects on the nasal mucosa Avotd use rn pa'rents wtth
`recent nasal ulcers nasal surgery or nasal trauma.
`
`Please see additional Important Safety Information throughout and Full Prescribing Information
`in pocket.
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULA TEO PROTECTIVE ORDER
`
`MEOA_APTX03474431
`
`PTX0916-00003
`
`3
`
`

`

`3 pivotal clinical studies of total nasal symptom scores showed
`
`RAPID RELIEF
`BECAUSE PATIENTS HAVE WAITED LONG ENOUGH
`
`Onset of nasal
`symptom relief
`as fast as
`
`minutesl
`
`vs placebo (P <.OS)
`
`Onset was defined as the first timepoint at
`which Dymista was significantly superior to
`placebo in the mean change from baseline
`in iTNSS and was sustained thereafter
`in patients 212'·•
`
`TNSS os caleulined as ttle sum of the pat-ents sronng ol the~ 1/11Jwiduat nasal symptoms irl11norr11e.1 congestm sneenng. nnd ncf1,ngl on .t 0 to 3 categor~e<1l
`seventy sea e 10-ab>anL I m1ld 2-moderate. 3~>verej
`
`Important Safety Information continued
`• Glaucoma or postenor subcapsular cataracts Mon1 or oat•ents closely wrth a change 1n v1510n or w1lh
`a r •story or .ncreased Intraocular pressure glaucoma and/or catarac s.
`• Paten 1al worsenrng of exrstrng tuberculosrs. fungal. bacterial. vrral, or parasrtrc ln'ectrons. o r ocular hNoes
`s1mplex. More senous or even latal course of chickenpox or measles 1n suscept•ble pat1ents Use caution 111
`par1ents WI h the above because of the potent1al for worsen1ng of these 1nfect•ons
`• Hypercor •c•sm and adrenal suppress•on w1th very h•gh dosages or at he regular dosage rn suscep •ble
`1nd1v1duals If such changes occur d1scont1nue DYMISTA slowly
`
`Please see additional Important Safety Information throughout
`and Full Prescribing Information in pocket.
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`MEDA_APTX03474432
`
`PTX0916-00004
`
`4
`
`

`

`DYMISTA®
`
`(azelastine hydrochloride and
`fiuncasone propionate) Nasal Spray
`137 meg/ 50 meg per Spray
`POLLEN MISERY DEFLECTED
`
`SUPERIOR EFFICACY
`VS AZELAST/NE HCL OR
`FLUTICASONE PROPIONATE COMPARATORS
`
`Dymlsta demonstrated significantly greater improvement in reflective total nasal
`symptom relief in patients 12' •
`
`MAGNITUDE OF NASAL SYMPTOM RELIEF
`
`M
`
`\
`
`EN
`
`t
`t
`The azelastine HCI and
`,r t
`t
`1
`1
`fluticasone propronate comparators were delivered via the same device and vehicle as Dymista and
`are not commercially available.' •
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULA TEO PROTECTIVE ORDER
`
`MEOA_APTX03474433
`
`PTX0916-00005
`
`5
`
`

`

`A supportive SAR trial showed
`
`SIGNIFICANT IMPROVEMENT
`VS PRODUCTS YOUR PATIENTS MAY HAVE TRIED
`
`Dymista demonstrated significantly greater improvement in total nasal symptom relief
`vs Astelin (azelastine HCI) or generic Flonase (fluticasone propronate) in patients 122 4
`
`MAGNITUDE OF NASAL SYMPTOM RELIEF
`
`0
`
`t.
`
`Important Safety Information continued
`• Potential reductton tn growth veloctty tn chtldren Monttor growth routtnely tn pedtatnc oa ents receMng
`DYMISTA
`
`Please see additional Important Safety Information throughout
`and Full Prescribing Information In pocket.
`
`V
`
`I
`
`1#4 '-oL)
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`MEDA_APTX03474434
`
`PTX0916-00006
`
`6
`
`

`

`DYMISTA®
`
`(azelastine h)Urochlonde and
`fiuticasooe propionate) Nasal Spray
`137 meg/50 meg per Spray
`POLLEN MISERY DE hE• D
`
`A supportive SAR trtal showed
`
`SUSTAINED IMPROVEMENT
`VS PRODUCTS YOUR PATIENTS MAY HAVE TRIED
`
`Dymista demonstrated significantly greater improvement in tota l nasal symptom relief
`vs active comparators and placebo over t ime (P< 001) in patients 12M
`
`SUSTAINED IMPROVEMENT OVER 2 WEEKS
`
`8
`
`<1>
`Ol c
`"' L u
`c
`re"' E ~
`"'
`l{l"' OiE
`Sl~
`"' "' ~
`Lf) z
`
`VJ
`
`f-
`
`•
`
`• A!,t In
`(r 152)
`
`S udy 1ay
`A ger er c F- OI'IC!<
`en 151)
`
`etla e
`(n 151)
`
`Ps.OI 'IS Asl~'" , ~nenc Fionase and placebo.
`P< 01 vs Aslel1n and placebo.
`
`•
`
`1 nt
`
`'1"
`
`Dn 2
`
`Important Safety Information continued
`• Potent inhibitors of cytochrome P450 CCYP) 3A4. May 1ncrease blood levels of flut1casone prop1onate.
`• Ritanov1r CoadministratiOn 1s not recommended
`• Other potent CYP3A4 1nhib1tors. such as ketoconazole: use caution w1 h coadm1nis rat1on
`· The most common adverse reactions react1ons (22% incidence) are dysgeusia, eplstax•s. and headache
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULA TEO PROTECTIVE ORDER
`
`MEOA_APTX03474435
`
`PTX0916-00007
`
`7
`
`

`

`SAFETY AND TOLERABILITY
`DYMISTA HAS BEEN WIDELY STUDIED IN >4000 PATIENTS
`
`Adverse reactions occurring wtth
`2% incidence and more frequently
`than with placebo'
`
`Dysgeusia
`
`Epistaxis
`
`Headache
`
`4%
`
`2%
`
`2%
`
`2%
`
`2%
`
`<1%
`
`2%
`
`mal:;n' IStnal•. ar open·o.lllel at'io-<:C"Uolled 'ud>i n•·1tld14G4pallents t2years01ageandoldel wtlhC/11onrc
`I spray per oostn ~"·00 da , and 207 IJ<lileniS \'o'Jre reated l'filh t IC<lSOne prOI)IQI'late
`I '
`•• treated wrlll Dymb
`
`Please see additional Important Safety Information throughout
`and Full Prescribing Information in pocket.
`
`0
`
`(.
`
`,
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`MEDA_APTX03474436
`
`PTX0916-00008
`
`8
`
`

`

`DYMISTA®
`
`{azelastine hydrochlorid~ and
`HutiGlSO~ propionat~) Nasal Spray
`137 meg/50 meg per S~y
`POLLEN MISERY OEFLECTEO
`
`SAFETY AND TOLERABILITY
`IN CHILDREN 6-77 YEARS OF AGE
`
`Adverse reactions occurring with 2% incidence and more frequently than with placebo'
`
`Dymista
`
`placebo
`
`Overall incidence
`
`Dysgeusia
`
`Epistaxis
`
`lr
`
`16%
`
`4%
`
`4%
`
`N
`
`12%
`
`0%
`
`3%
`
`1 spray per nostril, twice daily'
`
`Important Safety Information continued
`• Somnolence· Avo1d engag1ng 1n hazardous occupat1ons
`requ~r1ng complete mental aler ness such as dr.vmg or
`operating mach1nery when tak1ng DYMISTA
`• Avo1d concurrent use of alcohol or other central nervous
`system (C S) depressants WI h DYMISTA because urther
`decreased alertness and 1mpa1rment of CNS performance
`may occur
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULA TEO PROTECTIVE ORDER
`
`MEOA_APTX03474437
`
`PTX0916-00009
`
`9
`
`

`

`For seasonal allergic rhinitis sufferers 6 and older
`
`DON'T LET POLLEN GET THE BETTER
`OF YOUR PATIENTS
`
`Only Dymista offers fast relieta and inflammation control-with every dose1·2
`def!OOd as lhe f>rsl f mepoi,l 30 mtnutes al ~hEn [)ym ta .vas SlfJ'lfotalltlv ~nor I~ pJaQ;bo m th'.:
`~ d on ~ral·ld n e>:ll en" 12 and Oldef last 1e
`p n scote oTNSS! aoo was sustaoroeil m •rea«er
`mean change 11omb; ;el m IOSiillUaneOuS 1 Ia nas;''
`
`"' 1 spray per nostril, twice daily'
`
`"' 30 minutes fast
`
`.,.. 90% greater improvement '
`
`'"
`
`I•
`
`0,
`
`Dymista: Low spray volume at the maximum recommended adult dose'·5•6
`Product
`Astelln '
`generic Flonase·
`Astelin '
`genome Flonase '
`+
`(azelastine HCI)'
`(flutlcasone
`(azelastine HCI)
`(flutocasone
`propionate)'
`propionate)
`
`Dymtsta
`
`There IS no demonstraled clinical benefit regarding spray volume.
`lrtl
`AI ma"m tm '" on mt.nd !d adulf doso, ol 2 p lVS
`"
`Important Safety Information continued
`• Epis axts. nasal ulcera tons. nasal septal per ora •on. mpa1red wound healing Cand1da a!D1cans onfec ton
`Mont tor patoents penodtcally tor stgns of adverse effec son the nasal mucosa Avotd use tr pa oents wtth
`recent nasal ulcers. nasal surgery, or nasal trauma
`• Glaucoma or postenor su capsular cataracts Monttor pat tents closely wtth " ch nge on VtSoon or woth
`a htstory of tncreased tntraocular oressure. glaucoma. and/or cataracts
`
`Please see additional Important Safety Information
`throughout and Full Prescribing Information in pocket.
`,;
`
`DYM/STACOM
`
`MEDA ~.~J.~:=-..,._ .. _.,
`
`-"'
`
`DYMISTA®
`
`(azelastine hydrochloride and
`fiuticasone prop1011ate) Nasal Spray
`137 meg/50 meg per S~ay
`POLLEN MISERY DEFLECTED
`
`·=-
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULA TEO PROTECTIVE ORDER
`
`MEOA_APTX03474438
`
`PTX0916-0001 0
`
`10
`
`