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`Integrated Phase III Clinical Trials of Low-Concentration, Modified
`‘ ’f3S—4383
`Bromfenac Ophthalmic Solution Dosed Once Daily for Cataract Surgery
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`J.A. Gow,1 D.F. Goldberg} J.H. Peace,3 T.R. Walters,“ J.P. Gira,5 S.M. KIier,1 T.R. McNamara1
`for the Low Concentration Bromfenac Ophthalmic Solution Once Daily Study Group
`1Baus.ch & Lomb Inc‘, Irvine, CA; 3Wo|stan Eye Associates, Torrance, CA; -‘United Medical Research Institute, Inglewood, CA; *"lexan Eye, Austin, TX; Sophthalmology Consultants, Ltd, St. Louis, MO
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`Contact information:
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`’.r‘~;;i9s:i§.>-:1 To evalualn the efficacy and safety of low-concentration,
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`0 Phase 3, placebo—contrcl|ecl,
`modified bromfenac solution dosed QD for cataract surgery.
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`(n— 18} QD. Dosing began 1 day before cataract surgery and
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`Mean
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`v. Subjects received either bromfenac (n=222) or placebo
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`3 ‘A 50
`center study
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`continued daily through posbsurgery Day
`3
`14. Primary efficacy
`5 3
`0 440 subjecls randomized (222 in the bromfenac group, 218 in the
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`Early D's°°""““at'°"s- - -
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`3:
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`endpoint was no ocular inflammation by Day 15; secondary efficacyend oint was no ocular ain at Da 1
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`5 .5: ’“
`placebo group)at 39 clinical sites
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`tSe:E;3:;t:n:’V::TfY'5C°“t'“Ued
`34 (153%)
`95 (4439/D)
`'5 Eligible subjects were scheduled for a unilateral cataract surgery
`$<.+.o:..::-V Brornfenac was superior
`to placebo for primary and
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`(phacoemulsification or extracapsular) with PCIOL implantation
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`1 *1/c Compliance : mi: y ViU'l'-'l‘i9f of cases received X 1+3
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`‘ Sub ects'w,erje‘as'si,grie:d tojreceive[eithe‘,r ljromfenaq sodium
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`QD is safe and effective to treat the inflammation and pain associated
`.L-u.-Iron Lov\-concentration, modified bromfenac solution dosed
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`eligible for <:lini<:al,li’ial
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`Primary efficacy endpoint was clearance ofocularr ;
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`inflammatiorrisummed Ocular Inflammation Score (sols) = .
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`4 Secondary efficacy endpoint-was proportion ofsiibjects pain-
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`.5ubjeJct5 ,—aru?:ed to mg officeyan D(ay 1 for evaluation nfsgafbyty
`and efficacy
`~Sr.il:rjects returned to the office on Day 311 forerraluation of
`safety and efficacy
`‘Subjects returned to the office on Day 81:1 for evaluation of
`safety and efficacy
`-Discontinued test agent on day 14a:-id subjects returned to the
`Office 0" Dav 151:1 FM EVBIUEUOH ofsafelv and Em?-3CY
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`75,931,,
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`Bramfenac
`(ii = 2 12)
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`43 (2110/°)
`15 (7-'3°/t')
`11 (54%)
`8 (3.9%)
`8 (3-9%)
`5 (2 5%)
`‘
`S (2.5%)
`0
`5 (25/0)
`4 (10%)
`
`Adverse Brent
`Subjects reporting an AE affecling
`14 (66%)
`the study eye or both eyes
`6 (18%)
`E‘/E P33"
`5 (24%)
`Anteriw chamber inflammamn
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`2 (0.9%)
`Conjunctival hyperemia
`1 (0-5°/0)
`l°l‘<3t°Ph‘3b|3
`1 (0 5%)
`Corneal edema
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`1 (0.5%)
`Lacnmation increased
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`gcuiar hypemmia
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`'4 The incidence of CME/ME was 0.5% (1/212) in the bmrnfenac
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`group compared wit
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`randomized, double-masked, multl-
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`* P < 0.0001
`Day 15
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`Follow—up Phase: Day 22+3 or 7+3 Days After Final Dose
`» Subjects returned to the office on Day mm or 7+3 days after
`discontinuation oftest agent for termination evaluation
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`I‘”w'c°"ce"t"'fi°"' modified bromfenac s°h'fi°" dosed QDI
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`associated with cataract surgery.
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`'1 Bromtenac is a non-steroidal anti inflammatory drug (NSAID) with
`an extensive history of cllnicl efficacy;
`it acts by blocking
`prostaglandin synthesis by inhi
`ting cyclooxygenase 1 and 2 in
`the arachidonic acid pathway 1
`’» The bromine moiety in bromfenac enhances lipophilicity and
`facilitates penetration throughout ocular tissues 3'3
`'- Bronuck® (bromfenac sodium ophthalmic solution) 0.1% was
`initially approved in Japan in July 2000 and was subsequently
`approved for the treatment of blepharitis, conjunctivitis, scleritis
`(including episcleritis) and post-operative inflammatiom
`){ibrom‘"‘
`(lziromfenac ophthalmic solution) 0.09%, administered
`twice daily, was approved by the Food and Drug Administration
`(FDA) on March 24, 2005 for the treatment of patients with post-
`cataract ocular
`inflammation, and in January 2006 for
`the
`treatment of ocular pain following cataract surgery‘
`.
`.
`..
`V Bromday” (bromfenac ophthalmic solution) 0.09% administered
`once daily, was approved by the FDA on October 16, 2010 for the
`treatment of postoperative inflammation and reduction of ocular
`pain in patients who have undergone cataract extraction‘
`"’ B35“ 0" eXtei"5lV9 P°5t'm3"k9tl"‘9 eXP9Vle"‘C9 5"‘d data fmm
`clinical trials, bromfenac ophthalmic solution has demonstrated a
`favorable safety profile
`0 The modified formulation of bromfenac facilitates
`lntraocular
`penetration,
`thereby allowing a
`lower medication load while
`maintaining clinical efficacy with once daily dosing
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`0 To evaluate the efficacy and safety of low-concentration, modified
`bromfenac sodium ophthalmic solution dosed once daily for the
`treatment of ocular inflammation and ocular pain associated with
`cataract
`surgery in
`subjects who have undergone cataract
`extraction with posterior chamber intraocular lens implantation
`
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`Age (veers)
`Mean (so)
`Sex
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`Presented at the 2012 Annual Meeting of the hmorican Academy of Ophthalmology, November 10-13, 2012, Chicago, IL
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`Page 1 of 1
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`SENJU EXHIBIT 2227
`LUPIN v. SENJU
`IPR2015-01097