g&§‘3§§;§°§ ‘ agfig Randomized, Placebo-Controlled, Integrated Phase III Clinical Trials of a Once Daily, Low-
`125 / C0130
`Concentration, Modified Bromfenac Ophthalmic Solution Following Cataract Surgery:
`
`Focus on Zero to Trace Anterior Chamber Inflammation
`
`J.A. Gowl, J.D. Boyce’, H.J. Reiseri, R. Berry‘, J.T. Dao5, and S.P. Chandler‘
`for the Low Concentration Bromfenac Ophthalmic Solution Once Daily Study Group
`ifiausch & Lomb lnc., Irvine. CA, =0ranoe County Ophthalmology Medical Group, Garden Grove. CA, ‘Eye Care specialists, Kingston. PA, ‘Eye Care Arkansas PA Little Rock, AR,
`'»comea Consultants of Anzona. Phoenix, AZ
`
`Rrvsisits
`
`
`
`Anterior Ch-bar Cells
`
`Anterior C
`
`raiser flare
`
`Cell Gaunt
`
`Grade
`
`Flare Count
`
`?~1¢:l?::.~..I,i'.«'
`-.7:-.-shgn 74:12} .‘n)i)}-:-r::.~:
`
`x Phase 3, placebo-controlled,
`randomized. double-masked, multi-
`center study
`’ 440 sub)ecB randomized (222 in me brornfenac group, 218 in the
`placebo 9roup)at 39 clinical sites
`r Ellurble subyects were scnedued lor a milaberal cataract surgery
`(phacoemulsilication or extzracapsular) with PCIG. implantation
` 0 (Jamplate absence
`Screeningimaee: new -8 in -I.
`
`
`:- Subjects were aesiaied to receive either btoeifenec
`1-5 cells (trace)
`aplitieloiic solution or placebo dated QD
`
`
`- Subjects rniut have met inclusion and exclusion criteria to be
`dlgble for clnlca! till
`- Vrimery efficeq andaoint was clearance of ocular
`
`
`
`
`infiarnliatien [SI.lnlI¢dOtn|I Inflammation score (5015) =
`
`
`0] by fiv IS
`
`
`- secondary efficacy endpoint was proportion of subjects will
`trace inflammation (sols: 0-05)
`
`
`
`6-15
`
`16-25
`
`26-S0
`
`> 5°
`
`Very sllght (barely valhle)
`
`Moderate (iris and lens clsr)
`
`Marked (iris and lens hazy)
`.
`.
`1"‘-EM! ("bflfl Cb!)
`
`/., Yreallient Phase: Day -1 to Day 15
`-Subjects began dosing on Day-I (~ 24 hours before Iirgery)
`-sdaiects returned to the officle on Day 1 for evaluation of
`
`,
`. “kw”, mu“: my “,3 or 7+3 Dav‘ Am, Hm. Do“
`__
`- subjects returned to the olflce on Day 21+:-I or 7«r3 days after
`discontinuation of lest agent for Iarrnlnauon evaluation
`
`,-
`
`,
`So:
`F=m~i-1
`
`
`
`‘
`n tn: ante 1
`
`l. ‘,
`l-!, a-.515 Ssfat-, us:
`Elllli. aJ-(I2 =.
`
`
`.-mp
`.
`3'l'l|'i5V ,Ini73
`-‘-v:l:.n:4 -’ill)'llr'§Fi'9 Ila:
`
`
`
`
`
`I‘! :'v- 304-:
`: l-,
`De
`’
`
`
`
`of 91;]
`[rCC<DrtI<:l'
`cu; um-um-i z
`
`
`
`T Cllél blD'll"E‘l3l: Cfirlrlalplll 5JlU[I'JI'I JJSEE
`IV
`'
`'
`Ualli:l'I
`
`uriiq .»
`nrxra r.-illu elf:-‘ilvell,
`‘rid <-for .-2.1..-s.-i n‘ my Inll.1'rrrlalIrri xnirriater.
`.\tl'
`‘mired ztzézzrz
`0 Bromfenac 5 a non-steroodd anti Inflamrnatory dnig [llSAlD) wth an
`extensive history of clinical efficacy;
`It mu by blocking pmelaghndln
`gzhmwfs, by Inmbmng "down-“S. 1 and 2 I" am amdmonk “Id
`7
`A The uomlne rnotety in uurnfeno: enhances Ipophiltlty and faulltaoas
`penetration throughout ocular bssua 5"’
`° Bronuckil [blomfenac aodluln ophthalmic solution) 0.1% was initially
`approved in Japan in lily 2000 and was subsequently spproied for the
`treatment of biepharitia, coiijuncflvlus. scierlua (including eplsclerlas) and
`past-operative lnfammauon‘
`A Xbrom” (bnomfenac ophthalmic solution) 0.09%, edmillaterd mite
`daily. Nu: -ppmv-1 by the road and Drug Mnunuu-at-on (rm) an rim»:
`24, 2005 for
`the uuovielt of patients with posbnararacx ocular
`inflammation, and In January 2006 for the troxinont of ocular pain
`follornrlq cataract surgery‘
`9 Bromday“ (bmrnfenac oohtilalmic solution) 0.09% administered once
`daily, was approved by the FDA on Ocmbec 16, 2010 for the treatment of
`pclstopermve iriflainmatlon a'id rmucmn of ocular pain In pments who
`have undergone zatarrict extraction‘
`'-* Based on extensive
`t-rnrkdlng experience and data from clinical
`trials, brornienac op malrrie solution has dernonstratnd a favorable
`safety profle
`° The
`advance!
`forrnilauor
`of
`broinfenac
`faclitztes
`Intraocuiar
`penetraoon, tr-erwy allowing a lower medication load wiiie maintaining
`clinics drlcacy ivltn once dallv dosing
`....
`E’«.:r;w.~.*7:;~.
`_
`_
`_
`trace anterior chamber inflarnrnation of
`inflammation to 0 or
`< To evaluate in a past-koc analysis
`the reduction of ocular
`.
`,
`.
`advanced formulation.
`lair-concentration, brvmfenac ophthalrnic
`Sfllllifin dosed once daily :ompared to placebo following cataract
`sugar in 2 hteqrated clincal trials.
`
`
`
`
`
`Pggoqnl; congilgnog
`Mean:
`Early Dleoontineatioes
`Subjects who discontinued
`96 (44.0%)
`34 (15.3%)
`test agent early
`52 (233%)
`7 (3.2%)
`Due to lack of efficacy
`Mr. |"lf‘l[lli-'(v'>'- : inn .- l'lfTlf>'( 'll:3*»';4 ya mun. .1
`lr‘.
`
`
`
`Mun: Eve“
`Subjects reporting an AE afiectirig
`the study eye or both eyes
`Eve Pain
`Anterior chamber inflammation
`Con]un:t'xvaI hy peremla
`Pliotuphobh
`
`H (6.6%)
`6 (2.8%)
`5 (2.4%)
`2 (0.9%)
`1 (O. 5%)
`
`4: (2i.1nx.)
`16 (7.8%)
`11 (5.4%)
`8 (3.9%)
`B (3.9%)
`
`1 (95%)
`1 (0.5%)
`
`COMBO‘ 269ml
`5 (25%)
`Lacrimaoon increased
`5 (2.5%)
`Foreign body sensation
`5 (2 9%)
`Ocular liyperemla
`4 (2.0%)
`
`
`\'."’:~’t(-- C3
`3' a s’
`t-lo: 2' ‘ ‘ms. 5
`F‘
`'2 The incidence of CMEIME was 0.5.
`1/212) in the bromfenac
`
`t
`9"°“" ‘°"‘l”'°‘ """" 2'0"“ (‘/2°‘) '" "‘° °"°"’° 9"""l"'
`x
`A
`gig.-3;‘-_-$,;5-,;g;;;s__:._;
`,
`_
`'°W'¢°||°¢fl*|'fl|°l|
`' AUVHVION‘
`'°|'m|ll3‘|°'|:
`bromfenac ophthalmic solution dosed once daily
`effectively
`and
`safely
`reduced
`ocular
`Inflammation associated with cataract surgery.
`' Once
`daily bromfenec ophthalmic
`solution
`0.07% was approved on April 5"‘, 2013 by the
`U.S. Food and Drug Administration (FDA) as
`PROt.ENsA"“
`
`
`
`‘rri.t‘:'eL-¢m\.'l.'I'
`llgvno"
`
`
`
`r'!lA'IIi-lA)Em:.\‘&L§‘\'IffiIoJmnti'¢ win on v.-.. -m\
`i
`....?..‘l..W....at..‘.u3.°?.
`L»:
`;
`...Z.n?.’..
`-
`vPV*a-r-uqurnivwri/'-It!
`Y «wt ,
`ei.
`.,
`lJ'_‘l
`p
`
`5
`E""""'*"'- "*W'""'*'“‘i"*‘ E °-"'31“
`3 mr;..:._i':m.:_tu:.xlu’=n;a . L‘orlwr:.wniv\cay' .un :m At.
`-‘I
`
`u
`K‘!!\U1'3h:a.‘lJ mm.-:i sauszna
`r. viz zen
`
`EK:lJ:hELcrTD lnc. .r‘-ire C-'-. LE»:
`Fiflall :4 ii:
`nr
`-:1 r......, :- 3..-., an :1 c.., .. uLrv.4l|<IlL. L4 Eat;-J
`3;; E-_-.t.
`
`
`
`lb I’: u .7-‘. 7 I‘ -'h.iri1-i an. -#711410-re. ill Flair
`
`
`
`PercentofSubjectsAchievingTraceInflammation
`
`
`
`Bromfenac 007% (n-222)
`"""Pl3C9b° (W218)
`
`
`
`gflzggdmelgriecgto the office on Day 3:1 fdrevaiuation of
`safety and efficacy
`-subjects returned to the office on Day on for evaluation of
`safety and etflarzy
`,
`-Discontinued host agent on day 14 and sulrjeae returned to the
`E_ office on Day 15:) for evaluation of safety and effiucy
`
`
`
` rmnau lnnmnmiofi-"‘
`I
`.r.
`i;c«. M11
`Preaeeted at tli 8!" Annual Meeting oi The Association for Research II Vision and Oplitlialeiology, Inc; May 5-9, 2013; Seattle, WA.
`LL
`L
`I’:
`C ll
`iv_ 3| AR’.
`I6-‘.l'r\-‘.l¢'Il
`§.l_i
`
`Page 1 of 1
`
`SENJU EXHIBIT 2224
`
`LUPIN v. SENJU
`1PR2"15'9110“ PROL0280756
`125 / C0130
`Concentration, Modified Bromfenac Ophthalmic Solution Following Cataract Surgery:
`
`Focus on Zero to Trace Anterior Chamber Inflammation
`
`J.A. Gowl, J.D. Boyce’, H.J. Reiseri, R. Berry‘, J.T. Dao5, and S.P. Chandler‘
`for the Low Concentration Bromfenac Ophthalmic Solution Once Daily Study Group
`ifiausch & Lomb lnc., Irvine. CA, =0ranoe County Ophthalmology Medical Group, Garden Grove. CA, ‘Eye Care specialists, Kingston. PA, ‘Eye Care Arkansas PA Little Rock, AR,
`'»comea Consultants of Anzona. Phoenix, AZ
`
`Rrvsisits
`
`
`
`Anterior Ch-bar Cells
`
`Anterior C
`
`raiser flare
`
`Cell Gaunt
`
`Grade
`
`Flare Count
`
`?~1¢:l?::.~..I,i'.«'
`-.7:-.-shgn 74:12} .‘n)i)}-:-r::.~:
`
`x Phase 3, placebo-controlled,
`randomized. double-masked, multi-
`center study
`’ 440 sub)ecB randomized (222 in me brornfenac group, 218 in the
`placebo 9roup)at 39 clinical sites
`r Ellurble subyects were scnedued lor a milaberal cataract surgery
`(phacoemulsilication or extzracapsular) with PCIG. implantation
` 0 (Jamplate absence
`Screeningimaee: new -8 in -I.
`
`
`:- Subjects were aesiaied to receive either btoeifenec
`1-5 cells (trace)
`aplitieloiic solution or placebo dated QD
`
`
`- Subjects rniut have met inclusion and exclusion criteria to be
`dlgble for clnlca! till
`- Vrimery efficeq andaoint was clearance of ocular
`
`
`
`
`infiarnliatien [SI.lnlI¢dOtn|I Inflammation score (5015) =
`
`
`0] by fiv IS
`
`
`- secondary efficacy endpoint was proportion of subjects will
`trace inflammation (sols: 0-05)
`
`
`
`6-15
`
`16-25
`
`26-S0
`
`> 5°
`
`Very sllght (barely valhle)
`
`Moderate (iris and lens clsr)
`
`Marked (iris and lens hazy)
`.
`.
`1"‘-EM! ("bflfl Cb!)
`
`/., Yreallient Phase: Day -1 to Day 15
`-Subjects began dosing on Day-I (~ 24 hours before Iirgery)
`-sdaiects returned to the officle on Day 1 for evaluation of
`
`,
`. “kw”, mu“: my “,3 or 7+3 Dav‘ Am, Hm. Do“
`__
`- subjects returned to the olflce on Day 21+:-I or 7«r3 days after
`discontinuation of lest agent for Iarrnlnauon evaluation
`
`,-
`
`,
`So:
`F=m~i-1
`
`
`
`‘
`n tn: ante 1
`
`l. ‘,
`l-!, a-.515 Ssfat-, us:
`Elllli. aJ-(I2 =.
`
`
`.-mp
`.
`3'l'l|'i5V ,Ini73
`-‘-v:l:.n:4 -’ill)'llr'§Fi'9 Ila:
`
`
`
`
`
`I‘! :'v- 304-:
`: l-,
`De
`’
`
`
`
`of 91;]
`[rCC<DrtI<:l'
`cu; um-um-i z
`
`
`
`T Cllél blD'll"E‘l3l: Cfirlrlalplll 5JlU[I'JI'I JJSEE
`IV
`'
`'
`Ualli:l'I
`
`uriiq .»
`nrxra r.-illu elf:-‘ilvell,
`‘rid <-for .-2.1..-s.-i n‘ my Inll.1'rrrlalIrri xnirriater.
`.\tl'
`‘mired ztzézzrz
`0 Bromfenac 5 a non-steroodd anti Inflamrnatory dnig [llSAlD) wth an
`extensive history of clinical efficacy;
`It mu by blocking pmelaghndln
`gzhmwfs, by Inmbmng "down-“S. 1 and 2 I" am amdmonk “Id
`7
`A The uomlne rnotety in uurnfeno: enhances Ipophiltlty and faulltaoas
`penetration throughout ocular bssua 5"’
`° Bronuckil [blomfenac aodluln ophthalmic solution) 0.1% was initially
`approved in Japan in lily 2000 and was subsequently spproied for the
`treatment of biepharitia, coiijuncflvlus. scierlua (including eplsclerlas) and
`past-operative lnfammauon‘
`A Xbrom” (bnomfenac ophthalmic solution) 0.09%, edmillaterd mite
`daily. Nu: -ppmv-1 by the road and Drug Mnunuu-at-on (rm) an rim»:
`24, 2005 for
`the uuovielt of patients with posbnararacx ocular
`inflammation, and In January 2006 for the troxinont of ocular pain
`follornrlq cataract surgery‘
`9 Bromday“ (bmrnfenac oohtilalmic solution) 0.09% administered once
`daily, was approved by the FDA on Ocmbec 16, 2010 for the treatment of
`pclstopermve iriflainmatlon a'id rmucmn of ocular pain In pments who
`have undergone zatarrict extraction‘
`'-* Based on extensive
`t-rnrkdlng experience and data from clinical
`trials, brornienac op malrrie solution has dernonstratnd a favorable
`safety profle
`° The
`advance!
`forrnilauor
`of
`broinfenac
`faclitztes
`Intraocuiar
`penetraoon, tr-erwy allowing a lower medication load wiiie maintaining
`clinics drlcacy ivltn once dallv dosing
`....
`E’«.:r;w.~.*7:;~.
`_
`_
`_
`trace anterior chamber inflarnrnation of
`inflammation to 0 or
`< To evaluate in a past-koc analysis
`the reduction of ocular
`.
`,
`.
`advanced formulation.
`lair-concentration, brvmfenac ophthalrnic
`Sfllllifin dosed once daily :ompared to placebo following cataract
`sugar in 2 hteqrated clincal trials.
`
`
`
`
`
`Pggoqnl; congilgnog
`Mean:
`Early Dleoontineatioes
`Subjects who discontinued
`96 (44.0%)
`34 (15.3%)
`test agent early
`52 (233%)
`7 (3.2%)
`Due to lack of efficacy
`Mr. |"lf‘l[lli-'(v'>'- : inn .- l'lfTlf>'( 'll:3*»';4 ya mun. .1
`lr‘.
`
`
`
`Mun: Eve“
`Subjects reporting an AE afiectirig
`the study eye or both eyes
`Eve Pain
`Anterior chamber inflammation
`Con]un:t'xvaI hy peremla
`Pliotuphobh
`
`H (6.6%)
`6 (2.8%)
`5 (2.4%)
`2 (0.9%)
`1 (O. 5%)
`
`4: (2i.1nx.)
`16 (7.8%)
`11 (5.4%)
`8 (3.9%)
`B (3.9%)
`
`1 (95%)
`1 (0.5%)
`
`COMBO‘ 269ml
`5 (25%)
`Lacrimaoon increased
`5 (2.5%)
`Foreign body sensation
`5 (2 9%)
`Ocular liyperemla
`4 (2.0%)
`
`
`\'."’:~’t(-- C3
`3' a s’
`t-lo: 2' ‘ ‘ms. 5
`F‘
`'2 The incidence of CMEIME was 0.5.
`1/212) in the bromfenac
`
`t
`9"°“" ‘°"‘l”'°‘ """" 2'0"“ (‘/2°‘) '" "‘° °"°"’° 9"""l"'
`x
`A
`gig.-3;‘-_-$,;5-,;g;;;s__:._;
`,
`_
`'°W'¢°||°¢fl*|'fl|°l|
`' AUVHVION‘
`'°|'m|ll3‘|°'|:
`bromfenac ophthalmic solution dosed once daily
`effectively
`and
`safely
`reduced
`ocular
`Inflammation associated with cataract surgery.
`' Once
`daily bromfenec ophthalmic
`solution
`0.07% was approved on April 5"‘, 2013 by the
`U.S. Food and Drug Administration (FDA) as
`PROt.ENsA"“
`
`
`
`‘rri.t‘:'eL-¢m\.'l.'I'
`llgvno"
`
`
`
`r'!lA'IIi-lA)Em:.\‘&L§‘\'IffiIoJmnti'¢ win on v.-.. -m\
`i
`....?..‘l..W....at..‘.u3.°?.
`L»:
`;
`...Z.n?.’..
`-
`vPV*a-r-uqurnivwri/'-It!
`Y «wt ,
`ei.
`.,
`lJ'_‘l
`p
`
`5
`E""""'*"'- "*W'""'*'“‘i"*‘ E °-"'31“
`3 mr;..:._i':m.:_tu:.xlu’=n;a . L‘orlwr:.wniv\cay' .un :m At.
`-‘I
`
`u
`K‘!!\U1'3h:a.‘lJ mm.-:i sauszna
`r. viz zen
`
`EK:lJ:hELcrTD lnc. .r‘-ire C-'-. LE»:
`Fiflall :4 ii:
`nr
`-:1 r......, :- 3..-., an :1 c.., .. uLrv.4l|<IlL. L4 Eat;-J
`3;; E-_-.t.
`
`
`
`lb I’: u .7-‘. 7 I‘ -'h.iri1-i an. -#711410-re. ill Flair
`
`
`
`PercentofSubjectsAchievingTraceInflammation
`
`
`
`Bromfenac 007% (n-222)
`"""Pl3C9b° (W218)
`
`
`
`gflzggdmelgriecgto the office on Day 3:1 fdrevaiuation of
`safety and efficacy
`-subjects returned to the office on Day on for evaluation of
`safety and etflarzy
`,
`-Discontinued host agent on day 14 and sulrjeae returned to the
`E_ office on Day 15:) for evaluation of safety and effiucy
`
`
`
` rmnau lnnmnmiofi-"‘
`I
`.r.
`i;c«. M11
`Preaeeted at tli 8!" Annual Meeting oi The Association for Research II Vision and Oplitlialeiology, Inc; May 5-9, 2013; Seattle, WA.
`LL
`L
`I’:
`C ll
`iv_ 3| AR’.
`I6-‘.l'r\-‘.l¢'Il
`§.l_i
`
`Page 1 of 1
`
`SENJU EXHIBIT 2224
`
`LUPIN v. SENJU
`1PR2"15'9110“ PROL0280756
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