TRANSMITTAL OF ADVERTISEMENTS
`AND PROMOTIONAL LABELING FOR
`DRUGS AND BIOLOGICS
`FOR HUMAN USE
`
`11126/2012
`
`2. LABEL REVIEW NO. (Boologocs}
`
`fonn and
`For multiple products. submit completed
`spedmen of advenisinglpromotlonal materials
`to one
`application of choice. and attach separate sheet
`addressing items 3-5 for remainder of products. Refer to
`No. 3 on Instruction sheet.
`
`Form Approved OMS No 0910-0001 Expiration Date· September 30 2014· see OMS Statement on Page 3
`3. NOAIANOAIAADA OR BUVPLAI?MA
`1. DATE SUBMITTED
`Number. 202-236
`Single product g) Multiple products 0
`
`NOTE: Form 2253 is required by law. Reports are required for approved NDAs and ANDAs (21 CFR 314.81)
`5 ESTABUSHEO NAME
`4. PROPRIETARY NAME
`azelastine hydrochloride and lluticasone propionate
`Prod . Code No.
`
`DYMI TA
`
`6. PACKAGE INSERT OATE and 10 NO.
`(latest final printed labeling)
`fN-023A6-01
`
`04/2012
`
`7 MANUFACTURER NAME.
`MEDA Pharmaceuticals, MEDA Pharmaceuticals Inc.
`License No
`IBiologocs)
`
`REVIEWED BY
`
`8
`
`Please check only one : g] Professional
`Material Type
`Dissemination!
`(use FDA codes)
`Publication Date
`a.
`
`b
`
`DATE
`
`FOAICBER USE ONLY
`RETURNED BY
`
`DATE
`
`AOVERllSEMENT I PROMOTIONAL LABELING MATERIALS
`0 Consumer
`
`Applicant's MateriaiiD Code and/or descnpbon
`
`c
`
`Previous review No.
`~ applicable I date
`(PLA Submission>)
`d
`
`COMMENTS:
`.pdf submitted
`
`-
`
`-
`
`-
`
`- - - -
`
`PSL
`
`...
`
`11/26/2012
`
`DYM-1 2-0240: AAM Ph~ sician's Deck
`
`~~~ -WLfO
`svtJ LJgs od.
`Lf'15! 7 r; It/
`
`/?;
`
`I
`I Add Continuation Page
`10 ;??I;~~
`
`I
`
`- 0
`
` Parlii/Flnal
`
`12. RESPONSIBLE OiiCIAf.:._)/
`
`a PHONE NO
`
`770.916.3918
`
`b. FAX NO.
`
`678-718.3253
`
`13 FOR CBER PRODUCTS ONLY: (Check one)
`0 Pant/Draft
`
`9. TYPED NAME AND TITLE OF RESPONSIBLE OFFICIAL OR AGENT
`Kimber! • Skopitz, RAC
`Manager. Regulatory Affairs
`11 APPUCANTS RETURN ADDRESS
`MEDA Pharmaceuticals inc.
`200 Nonh Cobb Parkway, Bldg. 400. Suite 428
`Marietta, GA 30062
`
`FORM FDA 2253 9111
`
`PREVIOUS EDITION IS OBSOLETE.
`
`Page 1 or J
`
`~ l'li>lnloqS......,.(lOI) .. )..G/<0
`
`Ef
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`PLAINTIFFS'
`TRIAL EXHIBIT
`
`PTX0917
`
`MEDA_APTX03478897
`
`PTX0917 -00001
`
`1
`
`CIP2085
`Argentum Pharmaceuticals LLC v. Cipla Ltd.
`IPR2017-00807
`
`

`

`TRANSMITTAL OF ADVERTISEMENTS
`AND PROMOTIONAL LABELING FOR
`DRUGS AND BIOLOGICS
`FOR HUMAN USE
`
`Form Approved· OMS No 091()..0001 E><piretion Date· September 30 2014· see OMS Statement on Page 3.
`1. DATE SUBMITTED
`3. NDAIANDAIAADA OR BLAJPLAJPMA
`Number. 202-236
`Single product ~ Muttiple products O
`For multiple products, submit completed
`form end
`•pedmen of advertising/promotional metertals to one
`application or choice. and attach sepera!e sheet
`addressmg items 3-5 for remainder of products. Refer to
`No. 3 on mstructlon sheet
`
`11 /26/2012
`
`2. LABEL REVIEW NO. (Btologics)
`
`NOTE: Form 2253 is required by law. Reports are required for approved NDAs and ANDAs (21 CFR 314.81)
`4. PROPRIETARY NAME
`5. ESTABLISHED NAME
`aze lastine hydrochloride and nuticasone propionate
`Prod. Code No.
`
`DYMlSTA
`
`6. PACKAGE INSERT DATE and 10 NO
`(latest final printed labeling)
`IN-023A6-0J
`
`04/2012
`
`REVIEW'ED BY
`
`8 .
`
`Please check only one: g) Prolesstonal
`Material Type
`Dtsseminationl
`(use FDA codes)
`Publication Date
`
`a.
`
`b
`
`7. MANUFACTURER NAME·
`M DA Pharmaceuticals, MEDA Pharmaceuticals Inc.
`Ucense No.
`IBioiOII;cs)
`
`DATE
`
`FDAJCBER USE ONLY
`RETURNED BY
`
`DATE
`
`ADVERTISEMENT I PROMOTIONAL L.ABEUNG MATERIALS
`0 Consumer
`
`Appltcant's Matertal iD Code and/or descnpton
`
`c
`
`Previous review No.
`if applicable I dele
`tPlA S~isslons)
`d.
`
`COMMENTS:
`.pdf submitted
`
`PSL
`
`11/26/2012
`
`DYM-12-0240: AAM Physician's Deck
`
`9. TYPED NAME AND TITLE OF RESPONSIBLE OFFICIAL OR AGENT
`Kimberly Skopitz, RAC
`Manager. Regulatory Affairs
`11. APPLICANT'S Kl: 1 UKN AOORt.::>::>
`
`MED Pharmaceuticals Inc.
`200 North Cobb Park\\ ay, Bldg. 400, Suite 428
`Mariena, GA 30062
`
`I Add Continuation Page I
`10;?,~~~
`-
`
`12 RESPONSIBLE oriCIAV/
`
`a PHONE NO.
`
`170.916.3918
`
`b. FAX NO
`
`678-718.3253
`
`13 FOR CBER PRODUCTS ONLY (Ched< one)
`D Pant/Draft
`
`D Part 11/Final
`
`FORM FDA 2253 9/11
`
`PREVIOUS EDITION IS OBSOLETE.
`
`l"'age 1 01 J
`
`PSCI'IIbii .... SoJ\l<<~"(l0 1J ~"" Ef
`
`HIGHLY CONFIDENTIAL
`-SUBJECT TO STIPULATED PROTECTIVE ORDER
`
`MEDA_APTX03478898
`
`PTX0917 -00002
`
`2
`
`

`

`,. ............
`
`(azelagme hydnxh
`and
`llbCaSOne p!llpiOOatl') Nasal Splay
`137 meg /SO ITK9 per Splay
`
`'In patients 12 years of •11• and oldtr wtlo
`azalaslln. hydroc:hlorldt and nutlcason. prop'-lt
`
`The following preaentalion It provided by Meda Ph•rmacaullcalt Inc,
`and does not qualify panlclpants for CME or other lndapend nt medlc.al
`education requirements, All mat.erials prnanted are ntanded to be
`consistent with FDA guidelines and supponlva of the approved Indication
`and label for the product described herein.
`
`Conllden~ 1. Not to be d~tttbuted, reproduced or al&etronlc•lly lnnsmltted.
`DYM 12-4ZAO
`
`Cover Slide
`Customized by Speaker and Date per meeting
`
`HIGHLY CONFIDENTIAL
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`

`Conf!d<.nllal. Not to bo dl>trlbub!d, rrprodua!d or •loctronlarlly tnrmmltted.
`DYM 12.0240
`
`We are now going to look at the unmet medical needs and some patient
`perspectives on SAR collected from market research .
`
`HIGHLY CONFIDENTIAL
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`

`AR-Frequently Underestimated and
`Inadequately Treated 1111![1!'!!11111~~~ii!P,!!I••
`
`Confl dentlal. Not to be distri bute<!, ntproducod or oloctronlally trariSmltted.
`DVM 12-4240
`
`Many patients do not respond sufficiently to treatment
`There are many patients who do not respond to therapy regardless of what is used to treat their
`symptoms.
`
`There exists several challenges when treating our AR patients. They include:
`
`1. Onset-Patients want something that works fast
`
`2. Approximately 75% of patients suffering from AR use multiple therapies, increasing costs(cid:173)
`Patients want something that is effective
`
`3. Patient dissatisfaction with current treatment is a leading cause of increased costs and
`adherence-Patients are still experiencing severe symptoms and are still seeking relief
`
`Survey Methodology:
`Harris Interactive conducted the online survey on behalf of AAFA from October 10-17, 2005,
`using its Chronic Illness Panel database. Total survey sampling includes a national sample of
`1214 U.S. adults aged (!18 years who have been diagnosed with seasonal allergies and are
`currently using prescription allergy medication to treat their allergies.
`Data are weighted to be representative of adults aged ~18 years who have been diagnosed
`with seasonal allergies and are currently using prescription allergy medication. Weighting was
`based on age within sex, education, race/ethnicity, region , income, and propensity to be online.
`In theory, with probability samples of this size, one can say with 95% certainty that the overall
`results have a sampling error of + 4.3 percentage points.
`Sampling error for the sub-samples of patients who see a health care professional for seasonal
`
`HIGHLY CONFIDENTIAL
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`

`allergies (n=1194), patients who are not satisfied with their current prescription
`allergy medication (n=348), and patients who are not satisfied with the allergy
`care provided by their doctor or health care provider (n=242) is higher and varies.
`This online sample is not a probability sample.
`
`HIGHLY CONFIDENTIAL
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`

`Confldontlal. Nollo bt! dlrtributrd, ropn>duud Of olectn>nlully lr.~n>mltted.
`OYM 12.0240
`
`We will now review some of the current therapeutic options to treat and manage
`SAR.
`
`HIGHLY CONFIDENTIAL
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`

`

`Management of Rhinitis:
`Multiple Thera peut;.;ic~O~p~t~io~n~s~~iii!!!ilill
`
`COnRdenll>l. Not to be dlsuibuted, rept"Oduce<l 01 electronically tronsmlttecl.
`DYM12-IINO
`
`As noted previously, as many as 75% of patients use multiple therapies to
`achieve symptom control.
`These are the major therapeutic classes of drugs used to treat SAR.
`Speaker opens a discussion with the audience:
`What are the agents you routinely employ? Why?
`
`HIGHLY CONFIDENTIAL
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`
`5
`
`MEDA_APTX03478904
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`
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`

`Patients Use Multiple Medications
`Looking for Relief
`
`Confldontlal. Not to be dl>trlbutod, roproclucod oroi<'Cir.,.,lcolly tnln>mlttod.
`DYM 12-G240
`
`Can you provide some insight on your therapy selection?
`
`Recall-Approximately 75% of patients suffering from AR use multiple therapies,
`leading to issues of increased costs.
`
`How can we become more efficient in our management of SAR?
`
`HIGHLY CONFIDENTIAL
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`
`MEDA_APTX03478905
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`

`Oral Antihistamines Plus Intranasal Antihistamine:
`Lack of Additive Benefit
`
`Confidontlill. Not t.o be dl<trtbutod, roproduad or olortronlc.ally tnorumlttod.
`DVM 1l.(ll•O
`
`Speaker Note: Please briefly review the methodology, primary efficacy variable, and results
`with the audience. It is important for them to appreciate the lack of added benefits to
`polypharmacy for SAR patients.
`
`Study Designs:
`Berger
`Two-week , multicenter, placebo-controlled , randomized , double-blind study in patients with moderate-to-severe
`symptoms of seasonal allergic rhinitis.
`Following a 1-week, open-label lead-in period, during which the patients received loratadine 10 mg daily, those
`patients who met the symptom qualification criteria (<25% to 33% improvement taking loratadine) were
`randomized to treatment with (1) azelastine nasal spray 2 sprays per nostril twice daily plus placebo capsule once
`daily, (2) azelastine nasal spray 2 sprays per nostril twice daily plus loratadine 10 mg tablets once daily, (3)
`desloratadine 5 mg tablets once daily plus placebo nasal spray 2 sprays per nostril twice daily, or (4) placebo
`nasal spray 2 sprays per nostril twice daily plus placebo capsule once daily.
`The primary efficacy variable was the change from baseline to day 14 in the total nasal symptom score,
`consisting of runny nose, sneezing, itchy nose, and nasal congestion symptom scores recorded twice daily (am
`and pm) in patient diary cards.
`1. Berger WE, et al. Ann Allergy Asthma lmmunol. 2003;91 :205-211 .
`
`LaForce:
`This was a multicenter, randomized , double blind, placebo controlled, 2-week study in patients with moderate-to(cid:173)
`severe seasonal allergic rhinitis.
`The study began with a 1-week, open-label lead-in period, during which patients received fexofenadine, 60 mg
`twice daily. Patients who improved less than 25% to 33% with fexofenadine were randomized to treatment with (1)
`azelastine nasal spray 2 sprays per nostril twice daily plus placebo capsules twice daily, (2) azelastine nasal
`spray 2 sprays per nostril twice daily plus fexofenadine 60 mg tablets twice daily, or (3) placebo nasal spray 2
`sprays per nostril twice daily plus placebo capsules twice daily.
`The primary efficacy variable was the change from baseline to day 14 in the total nasal symptom score (TNSS),
`consisting of runny nose, sneezing, itchy nose, and nasal congestion symptom scores.
`
`2. LaForce CF, et al. Ann Allergy Asthma lmmunol. 2004;93:154-159.
`
`HIGHLY CONFIDENTIAL
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`
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`
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`PTX0917 -00010
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`
`

`

`Speaker Note: Please initiate a discussion around these therapeutic choices for treating
`AR.
`
`Have you experienced similar results?
`
`What agents do you think would provide a benefit to your patients? Why?
`
`HIGHLY CONFIDENTIAL
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`7
`
`MEDA_APTX03478907
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`PTX0917 -00011
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`
`

`

`What To Do When a Patient Needs More Relief?
`
`Conflolenllol. NO! to be distributed, reproduto<l or ~IK!n>nlcally tron...,ltted.
`DVM 12.0140
`
`Is there a reason why we do this?
`
`HIGHLY CONFIDENTIAL
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`
`8
`
`MEDA_APTX03478908
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`
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`

`Confidontl•l. Not to be distribuU.d, reproduced or electJonlcally ttarumltted.
`DYM 12~2AG
`
`Naw
`
`DYMISTA
`
`We will now review some of the clinical data on Dymista rM.
`
`HIGHLY CONFIDENTIAL
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`
`9
`
`MEDA_APTX03478909
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`
`

`

`A Comprehensive Clinical Program Designed To
`Demonstrate Significant Superiority
`
`Confidontl•l. Not to be dlstrlbuted, reptoduced or electronlcolly tnn•mltted.
`DVM 12-ll2.0
`
`The 3 pivotal studies were designed to evaluate the efficacy and safety of
`Dymista TM to the 2 components of Dymista TM, azelastine HCI and fluticasone
`propionate, in a head-to-head comparison for rapid and more complete
`symptom relief of SAR.
`
`A long-term safety (12-month) study was conducted comparing Dymista™ to
`commercially available fluticasone propionate.
`
`The FDA recently provided guidance to industry on the clinical trial design for
`new formulations of 2 or more drugs when each drug alone has activity and can
`be administered individually.1
`
`Reference
`1. Center for Drug Evaluation and Research Guidance for Industry. Codevelopment of Two or More
`Unmarketed Investigational Drugs for Use in Combinations. December 2010.
`
`HIGHLY CONFIDENTIAL
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`
`10
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`MEDA_APTX03478910
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`
`

`

`Robust Sample Size and Comparative Trials To
`Demonstrate Significant Superio ·
`
`Confidential. Not to be distributed, "'produced or electronically transmitted.
`DYM 12-0:UO
`
`New
`DYMISTA-
`
`The clinical development program for Dymista TM enrolled over 4000 patients,
`surpassing the clinical programs used for approval of the 4 most recently
`approved drugs for the treatment of AR.
`
`*The 4 most recent drugs approved for AR had the following number of
`patients enrolled in their pivotal clinical trials: Patanase (1598); Veramyst
`(1829); Xyzal (2412); Astepro 0.15% (3077). None of these clinical trials
`involved head-to-head comparisons to current therapies. 1
`
`Each of the clinical trials designed for Dymista TM involved active comparators.
`The next slide provides a listing of the comparators used in each trial. The total
`enrollment for the Dymista ™ clinical trials totaled 4617 for all comparator trials.
`
`HIGHLY CONFIDENTIAL
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`
`

`

`Patient Inclusion: Pivotal Trials
`
`ConfldentloJ. Not to be dlstrlbllted, reprodU<td or tlmroniQJiy tronsmltttd.
`DYM 1Z-4ZAO
`
`The clinical trial program for DymistaTM Nasal Spray included four 2-week,
`randomized , double-blind , placebo- and active-controlled, parallel-group, clinical
`studies: MP4001 , MP4002, MP4004, and MP4006. These studies share several
`characteristics:
`Study population: patients aged ~12 years with symptomatic seasonal allergic
`rhinitis
`All had positive skin-prick tests to relevant pollen
`All patients had rTNSS scores of at least 8 out of 12 and a nasal congestion
`score of 2 out 3
`At least one of the following : disruption of sleep, emotional distress, work and
`school interference
`
`Speaker review rTNSS with the audience if needed
`
`HIGHLY CONFIDENTIAL
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`

`Efficacy and Tolerability of DYMISTA Were Evaluated in
`3 Well-Designed, Head-to-Head, Pivotal Studies
`
`1. Dymista PI
`Sect 14.1/p1511J7-
`8 & p11/111 & table
`2.
`
`2. DOF. 4002
`CSR, Synopsis. P
`4.J115 & 1 0; p5J111
`&4.
`
`4004 CSR,
`Synopsis. P 4.1!17:
`p 51113 & 6.
`
`4004 CSR,
`Synopsis P 4.J1)6;
`p5J1)2&5.
`
`Confldeni.la.l. Not to be dlltributrd, ..,produc~d or oloctronlcally tron.,lttod.
`OYM 12·0z.t0
`
`Efficacy and Tolerability of DYMISTA Were Evaluated in 3 Well-Designed,
`Head-to-Head, Pivotal Studies
`ista- PL-
`.-,_-oym-
`Sect 14.1/p1511J7·
`8 & p17J1)1 & table
`2.
`
`--,
`
`Key Takeaway:
`In a robust clinical development program, DYMISTA was evaluated in 3
`head-to-head studies that enrolled more than 3300 patients with SAR1·2
`Efficacy and tolerability of DYMISTA were compared with those of
`fluticasone, azelastine, and placebo (total of 4 study arms)
`
`Additional Information:
`Note that in these studies, fluticasone and azelastine were delivered
`2. ooF. 4002
`using the same vehicle as DYMISTA
`~~~· :~~~~~;
`In all studies, DYM ISTA, fluticasone, and azelastine were administered ris4·
`1 spray per nostril twice daily
`The study population was 12 to 78 years of age
`
`4004 csR.
`Synopsis. P 4.11f7;
`P 51113 & 6·
`4004 CSR,
`Synopsis. P 4.11J6;
`p 51112 & 5.
`
`References:
`1. Dymista [package insert]. Somerset, NJ: MEDA Pharmaceuticals Inc; 2012.
`
`HIGHLY CONFIDENTIAL
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`

`2. Data on file. MEDA Pharmaceuticals Inc.
`
`HIGHLY CONFIDENTIAL
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`
`MEDA_APTX03478914
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`
`

`

`Primary Endpoint
`
`Confidt!ntial. Not ta be dlsttlbuted 1 reproducrd or el~ronically tnumnlrted.
`DYM12-0240
`
`Primary endpoint: change from baseline to Day 14 in combined 12-hour AM
`and PM rTNSS
`
`Baseline-average of all combined rTNSS scores over 7 -day placebo lead-in
`period, including the AM day 1 diary scores (predosing)
`
`Patients used diary cards to record severity of their symptoms
`
`HIGHLY CONFIDENTIAL
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`
`MEDA_APTX03478915
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`

`Secondary Endpoints
`
`Confident!•!. otto be distributed, roprodu<ed or el<'<lronlcally transmitted.
`DVM 1Z.02AO
`
`Selected secondary endpoints:
`Change from baseline to Day 14 in individual symptom scores
`Onset of action
`Change from baseline in the RQLQ (overall score and 7 individual domains) in
`subjects aged ~18 years
`
`Individual symptom scores-Recorded change from baseline for individual symptom
`(nasal congestion, runny nose, itchy nose, and sneezing)
`
`Onset of action-Determined at the first office visit for each patient-nasal symptoms were
`scored at 15- to 30-minute intervals after the first dose of study medication during a 4-hour
`observation period.
`
`Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)
`28 items in 7 domains (activities, sleep, non-nose/eye symptoms, practical problems, nasal
`symptoms, eye symptoms, and emotional) evaluated on a 7 -point scale where O=no
`impairment and 6=maximum impairment.
`Administered to patients aged ~18 years.
`
`HIGHLY CONFIDENTIAL
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`

`An overall RQLQ score is calculated from the mean of all items in the
`instrument.
`A change from baseline of at least 0.5 points is considered a clinically
`meaningful improvement.
`
`HIGHLY CONFIDENTIAL
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`15
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`MEDA_APTX03478917
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`

`Results: Dymista™ Demonstrated Significant Improvement
`Compared To Placebo
`
`Conlldentlal. Not to be dlstrlbut•d. n>produce.d or elcdrunlc.olly tnnsmlttecl.
`oYM u .oz.a
`
`This graph represents the first part of the combination rule that Dymista TM was
`to be compared to placebo.
`
`It also represents the typical study design of recently approved AR therapies.1
`1. http://www.centerwatch.com/, Accessed 8.30.12
`
`Dymista rM showed improvement in rTNSS regardless of the allergy season
`when compared to placebo.
`
`HIGHLY CONFIDENTIAL
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`
`MEDA_APTX03478918
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`
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`

`Results: Dymista m Demonstrated Significant Improvement
`Compared To Fluticasone Propionate and Azelastine HC
`
`Confidomt.l. Not to be dlnrlbutod, "'PrudU<od or oll!d11>nlally tr.orumlttod.
`DYM 12.(1240
`
`This slide represents the find ings of the 3 pivotal studies with respect to the
`primary endpoint rTNSS.
`Across the 3 pivotal clinical trials, the improvement with Dymista m ranged
`from 40% to 67% greater improvement relative to either comparator 1·2
`The azelastine HCI and fluticasone propionate comparators used the same
`device and vehicle as Dymista m and are not commercially marketed 2
`Results shown are placebo subtracted
`
`Speaker Note: You may initiate a discussion on the data seen in the slide
`above.
`What are your thoughts regarding this data?
`
`Are there patients under your care that may be candidates for Dymista m
`now? Why?
`
`What would Dymista TM be replacing? Why?
`
`1. Dymista [package insert]. Somerset, NJ: Meda Pharmaceuticals Inc; 2012.
`2. Data on file. Meda Pharmaceuticals.
`
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`FDA Regulatory Guidance for Approval
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`18
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`DYM-12-0216 C..nfld<!ntlal. Not to 1M! dl.trtbutod, mpraducod or electronically tnommltlod.
`
`The FDA recognized that creating formulations of existing agents used together
`as a new single agent holds great promise for advancing patient care. Innovative
`drug, biological product, device combinations have the potential to make
`treatments safer, more effective, or more convenient or acceptable to patients.
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`Results: Rapid Symptom Relief
`
`Confld<lntlill. No! to IMI dlstribvtod, repruduatd or elt<tronlc.olly lr.lln<mltbld.
`OYM 12.0240
`
`Within 30 minutes of administration of Dymista™, patients began to
`experience significant relief of their nasal symptoms.
`
`How important is rapid relief to your patients? What impact will this have on
`your practice/prescribing for SAR?
`
`References
`1. Marple BF, Fornadley JA, Patel AA, et al. Keys to successful management of patients
`with allergic rhinitis: focus on patient confidence, compliance, and satisfaction. Otolaryngol
`Head Neck Surg. 2007;136:S107-S124.
`2. Dymista [package insert]. Somerset, NJ: Meda Pharmaceuticals Inc; 2012.
`3. Data on file. Meda Pharmaceuticals Inc.
`
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`Results: Improved Quality Of life1•2
`
`Conlidtntlol. Not to be dlSirlbuted, reproduced or oledronlu!ly t llln•mirted.
`DVM 12-0240
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`Are these typical quality of life issues that your AR patients present with? How do
`you address them currently?
`
`This information is supportive of the more complete symptom relief seen with
`DymistaTM.
`
`In the 3 pivotal trials, Dymista™ demonstrated a statistically significant greater
`decrease from baseline in the overall RQLQ than placebo
`Ranged from -0.55 (95% Cl: -0.72 , -0.39) to -0.80 (95% Cl : -1 .05, -0.55)
`
`The treatment differences between Dymista ™ Nasal Spray and the monotherapies
`were less than the minimum important difference of 0.5 points.
`
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`DYMISTA Delivers Substantially Less Spray Volume Than
`Concomitantly Administered Fluticasone and Azelastine
`
`1 Dymista Pl. Sect
`3/p~ .
`
`2. Flonase Pl. 2004.
`pMine 25; p 11/llnes
`424428.
`
`4. Aslelin Pl. 2011.
`p1f113; p8f114.
`
`Confidential. Not to be distribute<!, reproduced or etectroniQilV tron.,IUed.
`DVM 12.02.0
`
`DYMISTA Delivers Substantially Less Spray Volume Than Concomitantly
`Administered Fluticasone and Azelastine
`
`1 Dymista Pl.
`Sect 31p2f116.
`
`Key Takeaway:
`In comparison with the combination of fluticasone and azelastine(cid:173)
`administered as 2 separate sprays- DYMISTA delivers substantially less
`volume in a single spray, which can minimize throat rundown and nose
`runout1-4
`
`Additional Information:
`Patient surveys show that throat rundown and nose run out can affect
`patient preferences and adherence to treatment4·5
`It should be noted that practice guidelines state that there are inadequate
`data about the optimal interval between administration of an intranasal
`corticosteroid and an intranasal antihistamine, when administered as 2
`separate sprays6
`
`References:
`1. Dymista [package insert]. Somerset, NJ: MEDA Pharmaceuticals Inc; 2012.
`
`2 Flonase Pl.
`2004. p1nlne 25;
`p11nines 424-
`428.
`
`4. Astelin Pl.
`2011 . p1f113;
`p8f114.
`
`3. Meltzer 2007.
`p 18/c2J114;
`p19/c1f111 .
`
`6. Wallace
`2008. p
`S 19/table VI.
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`2. Flonase [package insert]. Research Triangle Park, NC: GlaxoSmithKiine;
`2003.
`3. Meltzer EO. Formulation considerations of intranasal corticosteroids for the
`treatment of allergic rhinitis. Ann Allergy Asthma lmmunol. 2007;96: 12-21 .
`4. Astelin [package insert]. Somerset, NJ: MEDA Pharmaceuticals Inc; 2011 .
`5. Mahadevia PJ , ShahS, Leibman C, Kleinman L, O'Dowd L. Patient
`preferences for sensory attributes of intranasal corticosteroids and willingness
`to adhere to prescribed therapy for allergic rhinitis : a conjoint analysis. Ann
`Allergy Asthma lmmunol. 2004;93:345-350.
`6. Wallace DV, Dykewicz MS, Bernstein Dl , et al. The diagnosis and
`management of rhinitis: an updated practice parameter. J Allergy Clin
`lmmunol. 2008;122(2):S1-S84.
`
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`Results : Adverse Reactions
`
`Confidonti•l. Not to be dl•trlbutod, ~produced or olectronlc.llytnon>mit1od.
`
`This table contains adverse reactions reported with frequencies greater than or
`equal to 2% and more frequently than placebo in patients treated with Dymista TM
`Nasal Spray in the seasonal allergic rhinitis controlled clinical trials.
`
`In these trials, somnolence was reported in <1% of patients treated with
`Dymista™ Nasal Spray (6 of 853) or vehicle placebo (1 of 861 ).
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`MP4000: Long-Term Safety Trial
`(12 Month, Open Label)
`
`PATIENT
`POPULATION
`
`• Patients >12 years
`with PAR or VMR
`
`• Oymlsta TM n=-405
`(1 spray per nostril
`2 limes dally)
`
`• Fluticasone n=207
`(2 sprays per nostril
`once per day)
`
`PRIMARY ENDPOINT:
`To evaluate safety and tolerability of
`Dymista '" over a 1-year period
`
`SECONDARY ENDPOINT:
`Change tn baseline in 12-hour rTNSS
`Change in Baseline from RQLQ
`
`Confidutlol. Nol to be distributed, reproduced or electronically transmitted.
`DVM 12-4240
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`• Study Design-randomized, 12-month, open-label, active-controlled , parallel-group study in
`subjects with perennial allergic rhinitis or vasomotor rhinitis
`
`1-week screening period preceded the 12-month treatment period
`
`Qualified subjects were randomized in a 2:1 ratio to treatment with :
`
`Dymista™ (1 spray per nostril twice daily= total daily dose 548 meg AZE; 200 meg
`FP)
`
`Fluticasone (2 sprays per nostril once daily=total daily dose 200 meg)
`
`• Clinic visits at months 1, 3, 6, 9, and 12
`
`• Phone contact at months 2, 4, 5, 7, 8, 10, and 11
`• Frequency of subject-reported adverse events
`Monthly contact to review diary cards
`• Focused nasal examinations
`Baseline, months 1, 3, 6, 9, and 12
`• Slit-lamp examination by an ophthalmologist
`Baseline, months 6 and 12
`• Laboratory assessments
`Hematology, chemistry, urinalysis
`Fasting AM serum cortisol levels at selected sites
`Baseline, months 6 and 12
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`• Efficacy assessment
`PM rTNSS baseline, daily over entire study period
`
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`Results: Long-Term Safety Trial
`
`Conflclen~al. Not to be cllftributed. reprodu<ecl or electronically t,.nl mlttecl.
`DYM 1Z-42AO
`
`• The overall incidence of adverse reactions was 47% in the Dymista™ Nasal Spray
`treatment group and 44% in the fluticasone propionate nasal spray group.
`• The most frequently reported adverse reactions (~ 2%) with Dymista TM Nasal Spray were
`headache, pyrexia, cough , nasal congestion , rhinitis, dysgeusia (2.5%), viral infection , upper
`respiratory tract infection, pharyngitis, pain , diarrhea, and epistaxis.
`• In the Dymista™ Nasal Spray treatment group, 7 patients (2%) had mild epistaxis and 1
`patient (<1 %) had moderate epistaxis. In the fluticasone propionate nasal spray treatment
`group, 1 patient (<1 %) had mild epistaxis. No patients had reports of severe epistaxis.
`
`• Somnolence was reported in <1% of patients treated with Dymista™ Nasal Spray
`
`• Less then 1% of treatment groups had adverse ocular effects
`In the Dymista™ treatment group, 1 patient had increased intraocular pressure at Month 6.
`In addition, 3 patients had evidence of posterior subcapsular cataract at Month 6 and 1
`at Month 12 (end of treatment).
`In the fluticasone propionate treatment group, 3 patients had evidence of posterior
`subcapsular cataract at Month 12 (end of treatment).
`
`• Effects of Dymista TM on the HPA axis were evaluated in a subset of patients
`Mean fasting serum cortisol levels were similar between patients treated with Dymista ™
`and patients treated with fluticasone at baseline, Month 6, and Month 12
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`HIGHLY CONFIDENTIAL
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`

`Dymista TM : Rapid And More Complete
`Symptom Relief
`
`Con-ntlot Not to be dl<trtbuted, reproduced or olectronla lly tronsmltto<I(cid:173)
`DYM 12-02AO
`
`• Previous clinical studies have shown that there is not an additional benefit in
`using an:
`Intranasal steroid with an oral antihistamine
`Intranasal antihistamine with an oral antihistamine
`
`• Market research has shown that patients want:
`Rapid (under 30 minute) relief from their symptoms of SAR
`Are willing to use multiple therapies to seek a more complete relief from
`the symptoms of SAR
`Are dissatisfied with their current therapies, especially during severe
`episodes
`
`• Dymista™ has demonstrated in clinical trials :
`Rapid onset of relief within 30 minutes compared to placebo
`Across the 3 pivotal clinical trials , Dymista has shown more complete
`relief vs. active comparators
`Treatment with Dymista also resulted in significant improvement in
`health-related quality of life (QoL) variables vs placebo
`
`HIGHLY CONFIDENTIAL
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`Confidential . Not to be dl>ltibutod, roproduced or electronically t"'nsmlned.
`DYM12~1CO
`
`Dymista TM is a unique fine mist formulation that contains both the antihistaminic
`properties of azelastine HCI and anti-inflammatory properties of fluticasone
`propionate
`
`Dymista TM demonstrated significant improvement in:
`TNSS vs monotherapy comparators*
`RQLQ vs placebo
`Onset of action vs placebo
`
`Adverse reactions: In each of the 2-week pivotal trials, incidence and types of
`adverse reactions were comparable in all treatment groups (N=3411)
`
`Conclusion:
`Dymista™ provides rapid and more complete relief from seasonal allergic
`rhinitis symptoms vs. fluticasone propionate or azelastine HCI
`
`*The azelastine HCI and fluticasone propionate comparators used the same device and vehicle as
`Dymista and are not commercially marketed.
`
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`ConHclentlal. Not to..., dl<tributl!d, repruclload or •ltctnxdaUy tronsndtted.
`
`DVM 1l.02AO
`
`We will now review some highlights of the prescribing information (PI) for
`DymistarM.
`
`Pis to be distributed to the attendees.
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`

`Indication and Usage
`
`of seasonal allergic rhinitis
`in patients 12 years of age
`and older who require
`treatment with both
`azelastine hydrochloride
`and fluticasone propionate
`for symptomatic relief.
`
`... .....,._ __ ........... ___ .. ......_, ___ , __
`"-·-.......... --
`, . ...,.... ,......,....__....., _____ ··-----·-
`.... _.,.._......, ___ ~ ............ _ ... _ .. _... ...
`. "'--.. ·---·--.--.-.... .... ,, .. _
`.. -----~·-·-
`
`r1 ----.•r·-o~-...-.....-•-,ot-I""P"-1''
`u _.._
`
`flo _ ,_ ,__ ..... 1 ____ ...... - - · -
`
`. ·----o~~--.. .... - .......... __ ..... "'
`...... ~----...--.......... ..,-
`
`Please see Full Prescribing Information.
`
`Confid•ntlill . Not to b.. dl.rtributod, n!pmduced or ele<tronl<.ally transmltte<L
`
`DVM 12-4240
`
`Dymista ™ Nasal Spray is indicated for the relief of the symptoms of seasonal
`allergic rhinitis (SAR) in patients 12 years of age and older who require
`treatment with both azelastine