DEFINITION/
`DEFINITION/
`BACKDROP
`BACKDROP
`
`Pharmaceuticals
`
`Urinary Incontinence
`
`New Therapies Expanding The Market
`
`Urinary incontinence (UI), the loss of bladder control or the
`leakage of urine, results from numerous causes, including
`
`pelvic muscle instability, pregnancy, surgery, urinary tract
`infections, and certain foods and medications.
` Urinary
`23% CGR 2003-08
`incontinence includes urge incontinence (characterized by a
`frequent desire to urinate) and stress incontinence (characterized by weak bladder
`muscles). Overactive bladder encompasses both increased urinary frequency and
`urge to urinate. More than 13MM Americans suffer from some form of urinary
`incontinence, and 18MM+ from overactive bladder. Pharmacologic therapies, pelvic
`muscle rehabilitation, and surgery are most frequently used to treat urinary
`incontinence and overactive bladder. Currently available pharmaceutical treatments
`address symptoms of urge incontinence but side effects are an issue. Stress and
`mixed incontinence account for over half of incontinence sufferers, providing a
`ready market for new therapies.
`
`Urinary Incontinence Category Market Share By $ Sales
`
`
`
`
`
`
`
`2003
`$1.3B
`WPI
`2%
`
`PARTICIPANTS
`
`JNJ
`29%
`
`2008P
`$3.9B
`
`Other
`9%
`
`WPI
`3%
`
`NVS
`10%
`
`JNJ
`14%
`
`PFE
`44%
`
`PFE
`69%
`
`LLY
`20%
`
`
`
`MAJOR TRENDS &
`ISSUES
`
`Pfizer’s Detrol/Detrol LA (tolterodine) franchise should continue to lead the
`overactive bladder/urge incontinence market through 2008, driven by the strong
`clinical profile of Detrol LA. J&J's Ditropan XL dollar share could decline given that
`newer therapies, including Watson Pharmaceuticals' Oxytrol, Indevus' Trospium,
`Novartis’ Enablex, and Yamanouchi/GlaxoSmithKline's Vesicare, may offer fewer side
`effects. Eli Lilly's Duloxetine, for stress and mixed urinary incontinence, should be a
`major force in this market.
`
`– The UI and overactive bladder patient populations are large, but difficult to
`penetrate given lack of effective therapies and embarrassment over the
`consequences of the ailments.
`
`– New drug therapies with improved side-effect profiles have brought many
`patients into the treatment stream. The move from generics to new treatments
`has "re -branded" the category.
`
` March 05, 2004
`
`
`
`519
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1059 - Page 1
`
`

`
`
`
`Pharmaceuticals
`
`– Branded products for urge incontinence and overactive bladder, led by Pfizer’s
`Detrol LA and JNJ’s Ditropan XL, appear comparable in terms of effectiveness and
`side effects. Oxytrol’s (Watson) improved side-effect profile and twice-weekly
`patch delivery system provide a differentiated alternative to oral anticholinergic
`therapies.
`
`Indevus’
`– Yamanouchi/GlaxoSmithKline's Vesicare, Novartis’ Enablex, and
`Trospium may improve upon the tolerability of current agents, although their
`mechanisms are similar. Head-to-head comparison studies will be required to
`claim superiority. Trospium appears most differentiated based on a lower CNS
`side-effect profile, but the current twice-daily dosing regimen will be a hurdle.
`
`– Eli Lilly's Duloxetine could double the potential market by targeting a new patient
`population of stress and mixed incontinence sufferers.
`
`– Our scatter plot shows that through 2008, Pfizer should dominate the
`incontinence market. Indevus should see the majority of its sales growth from
`this category.
`
`Urinary Incontinence
`
`IDEV
`
`WPI
`
`NVS
`
`JNJ
`
`GSK
`
`LLY
`
`PFE
`
`$0.20
`
`$0.40
`
`$1.40
`$1.20
`$1.00
`$0.80
`$0.60
`2008 Sales Contributed By Company To Category ($ In B)
`
`$1.60
`
`$1.80
`
`$2.00
`
`80%
`
`60%
`
`40%
`
`20%
`
`0%
`
`% Of Company 2003-08 Sales Growth From Category
`
`-20%
`$0.00
`
`520
`
` March 05, 2004
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1059 - Page 2
`
`

`
`
`
`
`
`Pharmaceuticals
`
`ESTIMATED U.S. MARKET FOR URINARY INCONTINENCE (STRESS + URGE) DRUGS*
`
`2003
`
`2004E
`
`2005E
`
`2006E
`
`2007E
`
`2008E
`
`CGR
`
`Comment
`
`+3%
`
`- 18MM+ Americans with overactive bladder
`
`22,827
`+3%
`100%
`22,827
`+3%
`49%
`11,071
`54%
`6,016
`54%
`3,273
`14%
`33,848 +16% - Newer products for urge incontinence and
`+13%
` 2005 introduction of Duloxetine for SUI
`
`+3%
`
`- Includes portion of patients with mixed UI
`
`- Patients seeking treatment increase with better
` diagnosis, availability of newer treatments
`- Drug therapy market share expected to climb
` significantly with introduction of Duloxetine
`- Newer products with fewer side effects and longer
` duration and new products for stress incontinence
`
`+8%
`
`+13%
`
`+17%
`
`35%
`11,723
`$2.70
`$1,130 +16%
`24%
`8,239
`
`$2.70
`$800
`17%
`5,804
`$2.70
`$550
`4%
`1,389
`$2.40
`$110 +37%
`6%
`2,011
`$2.70
`$190
`
`NA
`
`+8%
`
`NA
`
`- Once-daily LA launched 1/01
`- Improved side-effect profile compared to Detrol
`
`- Eli Lilly expected to launch in Q1:2005
`- Stress urinary incontinence; first in class product
`
`-
`- New treatments with lower side effects clip
`- Launched 2/99 for overactive bladder
`
`- Oxybutynin patch; improved side-effect profile
`- Marketed by Women's Health, GP Division & CSO
`
`- Sold by Pfizer to Novartis in Q1:2003
`- NDA Q1:2003; H2:2004 launch assumed
`
`- Side-effect profile clips potential
`
`- NDA Filing 4/03; H2 2004E launch
` U.S. trials positive on side effects/efficacy
`
`U.S. Population/Prescriptions (000's)
`Overactive Bladder Sufferers
` % Growth
` % With Urge & Stress Symptoms
`Urge/Urge Predominant UI Sufferers
` % Growth
`% Incontinence Pts Seeking Treatment
` Incontinence Pts Seeking Treatment
`Drug Therapy Market Share
`Incontinence Pts Placed On Drug Tx
`Drug Therapy Retention Factor
`Incontinence Pts Compliant With Tx
`% Incontinence Pts Compliant With Tx
`Number of Scrips Filled/Year
` % Growth
`
`Detrol LA (PFE) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Detrol LA Sales ($MM)
`Duloxetine (LLY) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Duloxetine Sales ($MM)
`Ditropan XL (JNJ/AZA) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Ditropan XL Sales ($MM)
`Oxytrol (WPI) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Oxytrol Sales ($MM)
`Enablex (NVS) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Enablex Sales ($MM)
`
`19,634
`+3%
`100%
`19,634
`+3%
`38%
`7,366
`44%
`3,209
`47%
`1,504
`8%
`15,837
`+5%
`
`40%
`6,382
`$2.40
`$545
`
`20,262
`+3%
`100%
`20,262
`+3%
`38%
`7,695
`45%
`3,461
`50%
`1,741
`9%
`18,296
`+16%
`
`43%
`7,865
`$2.50
`$700
`
`28%
`4,512
`$2.40
`$379
`2%
`331
`$2.15
`$23
`
`28%
`5,185
`$2.50
`$455
`4%
`752
`$2.25
`$55
`2%
`353
`$2.50
`$30
`
`Trospium (IDEV) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Trospium Sales ($MM)
`Vesicare (YM-905) Market Share
` Prescriptions (000's)
` Price Therapy/Day
`Vesicare Sales ($MM)
`8%
`Detrol (PFE) Market Share
`1,199
` Prescriptions (000's)
`$2.40
` Price Therapy/Day
`$102
`Detrol Sales ($MM)
`14%
`Generic Oxybutynin Market Share
`2,161
` Prescriptions (000's)
`$28
`Oxybutynin Generics Sales ($MM)
`$18
`Other Therapies Sales ($MM)
`$1,095
`U.S. Incontinence Drug Sales ($MM)
`+17%
` % Growth
`Source: SG Cowen estimates, IMS Monthly Prescriptions.
`* Patient population and scrips in 000's; sales in $MM.
`
`1%
`125
`
`$2.50
`$10
`1%
`125
`$2.50
`$10
`5%
`907
`$2.50
`$80
`9%
`1,700
`$22
`$19
`$1,381
`+26%
`
`20,890
`+3%
`100%
`20,890
`+3%
`41%
`8,565
`48%
`4,090
`52%
`2,139
`10%
`22,318
`+22%
`
`41%
`9,117
`$2.55
`$830
`10%
`2,224
`
`$2.55
`$200
`24%
`5,363
`$2.55
`$480
`4%
`967
`$2.35
`$75
`4%
`784
`$2.55
`$70
`
`3%
`577
`
`$2.55
`$50
`3%
`577
`$2.55
`$50
`3%
`654
`$2.60
`$60
`6%
`1,400
`$18
`$10
`$1,843
`+33%
`
`21,517
`+3%
`100%
`21,517
`+3%
`44%
`9,454
`51%
`4,811
`52%
`2,514
`12%
`26,082
`+17%
`
`38%
`10,019
`$2.60
`$930
`16%
`4,253
`
`$2.60
`$400
`21%
`5,479
`$2.60
`$500
`4%
`1,136
`$2.40
`$90
`5%
`1,209
`$2.60
`$110
`
`3%
`879
`
`$2.60
`$80
`3%
`879
`$2.60
`$80
`2%
`405
`$2.80
`$40
`5%
`1,270
`$17
`$13
`$2,260
`+23%
`
`22,163
`+3%
`100%
`22,163
`+3%
`47%
`10,350
`53%
`5,461
`53%
`2,899
`13%
`30,023
`+15%
`
`36%
`10,887
`$2.65
`$1,030
`21%
`6,273
`
`$2.65
`$600
`19%
`5,644
`$2.65
`$525
`4%
`1,263
`$2.40
`$100
`5%
`1,617
`$2.65
`$150
`
`4%
`1,078
`
`$2.65
`$100
`4%
`1,078
`$2.65
`$100
`1%
`405
`$2.80
`$40
`4%
`1,225
`$16
`$14
`$2,675
`+18%
`
`522
`
`
` March 05, 2004
`
`NA
`
`NA
`
`-17%
`
`- NDA Filing 12/02; H2:2004E launch
` GlaxoSmithKline co-marketing in U.S.
`
`- Continued conversion to LA
`
`- Price increases bolster switch to Detrol LA
`
`- Share decline with launch of new UUI therapies
`
`4%
`
`1,270
`$2.70
`$120
`4%
`1,270
`$2.70
`$120
`1%
`405
`$2.80
`$40
`4%
`1,225
`-11%
`$16
`-5% - Other generics (flavoxate, imipramine, etc.)
`$14
`$3,090 +23% - Improved treatments, better compliance
`+16%
` (Market sales include generics)
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1059 - Page 3
`
`

`
`
`
`Pharmaceuticals
`
`Detrol/LA and Ditropan XL Dominate The Treatment Market
`
`Both Detrol/LA and Ditropan XL are advances over prior therapy due to their
`reduced incidence of side effects (particularly dry mouth) and improved dosing
`regimen. Immediate-release oxybutynin generally is dosed at 2.5mg two or three
`times daily. At the 5mg dose, up to 70% of patients discontinue use of immediate-
`release oxybutynin within six months due to side effects, particularly dry mouth.
`Detrol is dosed at 2mg twice daily, with no titration. Detrol LA is dosed at 2-4mg
`once-daily and Ditropan XL is dosed at 5-30mg once daily, with the dose titrated to
`efficacy and patient tolerance. In the clinical studies published in the package
`inserts, Detrol and Detrol LA show superior tolerability to Ditropan XL, with dry
`mouth incidence reported at 39.5% for Detrol and 23.5% for Detrol LA, versus 60.8%
`for Ditropan XL. On the efficacy front, the drugs appear similar in their reduction
`(17-22%) of urinary frequency, although Ditropan XL may be superior in terms of
`reducing incontinence episodes. Detrol, Detrol LA and Ditropan XL garnered 80%+ of
`new prescriptions in the incontinence market in 2003.
`
`-
`
`Pfizer’s Detrol Franchise Holding Steady
`Detrol and Detrol LA have dominated
`the overactive bladder/urinary
`incontinence market. A wide-reaching patient and physician education program
`has increased treatment of incontinence and overactive bladder. Detrol is
`efficacious in reducing the number of micturitions and in increasing the volume
`voided per micturition, and Detrol LA has shown similar results with an
`improved dosing profile. The Detrol franchise continues to capture nearly 50%
`of new prescriptions, bolstered by once-daily Detrol LA. Detrol LA's NRx share
`decreased modestly to 41.0% in January 2004 from 41.5% in February 2003, and
`Detrol market share declined from 10.4% in February 2003 to 7.4% in January
`2004, trimmed by the launch of Watson’s Oxytrol. With Pfizer’s primary care
`reps currently promoting Detrol LA in the U.S., the Detrol franchise has
`maintained strong penetration of the general practitioner market. In January
`2004, nearly 54% of all Detrol LA prescriptions were written by general
`practitioners.
`
`Detrol LA Specialty Prescribers
`
`
`
`Jan-04
`
`Nov-03
`
`Sep-03
`
`Jul-03
`
`May-03
`
`Mar-03
`
`Jan-03
`
`Nov-02
`
`Sep-02
`
`Jul-02
`
`May-02
`
`Mar-02
`
`Jan-02
`
`Nov-01
`
`Sep-01
`
`Jul-01
`
`May-01
`
`Mar-01
`
`Jan-01
`
`UROLOGY
`
`GENERAL
`
`OB/GYN TOTAL
`
`OTHER
`
`250,000
`
`200,000
`
`150,000
`
`100,000
`
`50,000
`
`0
`
`Source: SG Cowen, IMS Monthly Prescriptions
`
`524
`
`
` March 05, 2004
`
`Petitioner Mylan Pharmaceuticals Inc. - Exhibit 1059 - Page 4