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MR guided MR guided Focused Focused Ultrasound Ultrasound SurgerySurgery

Payer Presentation

Non-invasive treatment for uterine fibroids

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• Benign growths in uterus, found in up to 77% of women, symptomatic in 25-30% in women aged 25-50 1,2

• Over 400,000 women annually undergo surgery for uterine fibroids• 177,000 to 366,000 hysterectomies• 40,000 myomectomies• 10,000 UAE

• 2-4 million work days lost before surgery

• 3-7 million work days lost after surgery.

• Symptoms 3-9 include:– Extensive bleeding/ anemia – Pelvic pain and/or pressure, cramping– Incontinence– Sexual dysfunction– Reproductive difficulties and complications during pregnancy

• Symptoms interfere with home, social and work life due to tiredness, weakness, lack of control and unpredictability

• Current treatment options place an undue burden on women

Uterine fibroids are common and debilitating

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Procedure Description Advantages Disadvantages Hysterectomy Surgical removal of the

uterus involves hospital stay and lengthy recovery period.

Permanent solution because the uterus is removed.

Reproductive potential is lost. Other side effects possible. Recovery time of several weeks.

Myomectomy Removal of one or more of the fibroids with open ab. surgery or laparoscopic or endoscopic techniques

Preserves the uterus and cervix.

Recurrence of fibroid symptoms possible if new fibroids grow.

Uterine artery embolization

The uterine artery is blocked with small particles; the fibroid is starved of its blood supply.

Symptom relief with shorter hospital stay than hyst. or myomectomy.

Risks include radiation, menopause, serious infection, bleeding, embolization of other organs.

MRgFUS Focused ultrasound waves used to heat and destroy fibroid tissue. MRI images used for treatment guidance and feedback.

Outpatient, no incisions, no radiation or anesthesia; quick return to normal life.

Fibroid recurrence not proven. Not suitable for persons contraindicated for MRI.

Hormone therapy

A drug treatment that causes fibroid shrinkage.

Non-surgical, conservative method of fibroid treatment.

Temporary. Causes menopausal symptoms. May result in rapid return of symptoms after treatment.

Watchful waiting

No treatment. On going monitoring.

Sometimes fibroid symptoms diminish with menopause.

Fibroids may continue to grow with an increase in symptoms.

Uterine fibroids treatment options

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Uterine fibroids treatment comparison

Watchful Waiting MRgFUS Myomectomy HysterectomyUAEDrug Therapy

Spectrum of Invasiveness

Return to Normal Activity -- 1 Day 10 Days 4-44 Days 28-56 Days

Hospital Days 0 0 1 Day 1-3 Days 2-5 Days

Procedure Time 0 3 Hours .75-2 Hours 1-3 Hours 1.5-3.0 Hours

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What is MR guided Focused Ultrasound (MRgFUS)?

Breakthrough non-invasive technology which combines:

• High intensity focused ultrasound beam that heats and destroys targeted tissue, non-invasively

• Magnetic resonance imaging system (MRI) which visualizes patient anatomy, and controls the treatment by monitoring the tissue effect in real time

.Click once to view

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How does focused ultrasound work?

Focused ultrasound generates heat, ablating tissue only at the focal point. The effect is similar to a magnifying glass used to focus the sun’s energy on

a single point.

1x 2 mm

10 x 30 mm

Spot sizes

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Why is MR guidance and control important?

3D anatomic information for exact tumor targeting

Beam path visualization for safe treatment

Real time MR thermometry to achieve planned outcome

Post treatment contrast imaging for evaluating treatment outcome

CLOSED LOOP

THERAPY

CLOSED LOOP

THERAPY=

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Benefits of MR guided focused ultrasound

• Non-invasive outpatient procedure - replaces invasive surgery

• No hospitalization

• No anesthesia - only limited conscious sedation

• No ionized radiation

• Next day return to normal activity

• Low rate of complications

• Reduced cost to healthcare system

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Clinical results

• 92% of patients have symptom severity improvement; 84.5% have significant

improvement of > 10 points*

• Improvement levels maintained for at least 2 years

• No serious adverse events. Most related to length of treatment and resolve with

analgesic after treatment

• Alternative treatments- rate similar to that of other non-hysterectomy procedures

* ExAblate® 2000 for the Treatment of Uterine Fibroids Summary of Semi-Annual Report to FDA,June 2006

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Disability days and provider encountersside by side comparison with Total Abdominal Hysterectomy

1.42.9

1.5

18.9

17.1

9.7

0

2

4

6

8

10

12

14

16

18

20

Missed Work Days From Normal Activities Days In Bed

Day

s

MRgFUS

TAH

With MRgFUS: 83% Fewer doctor visits66% Fewer additional diagnostic tests 66% Fewer additional procedures

MRgFUS uses significantly fewer medical resources

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Greater than 10 point improvement in Symptom Severity Score*• Disease specific validated measure for detecting differences in UF symptom severity

and health related quality of life: – eight questions related to fibroid specific symptoms: pain, bleeding and bulk; – twenty nine health-related quality of life questions with six subscales – Patient Satisfaction Survey– SF-36

• Demonstrated correlation with validated QOL instruments*

*James B. Spies M.D., Karin Coyne PhD, et.al. “The UFS-QOL, a new Disease-specific Symptom and Health-related Quality of Life Questionnaire for Leiomyomata. Obstet Gynecol 2002 Feb;99(2):290-300

Clinical endpoints

22.5

44

62

010203040506070

Women WithoutFibroids

Women WithFibroids

Women treated withMRgFUS during

Pivotal StudyPatient Group

Ave

rage

Sym

ptom

Sev

erity

Sco

re

MRgFUS patients were highly symptomatic

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Improvement in Symptom Severity Scores – by protocol

• Commercial treatment guidelines (Group B2) resulted in greater reduction in Symptom Severity at 3,6,12 and 24 months after MRgFUS.

• Majority of symptom relief experienced at 3M (first data point)

• Durable/sustained symptom relief Reference: SSS for women without fibroids

Mean SSS Over Time: UF005 Vs Pivotal Study

15

20

25

30

35

40

45

50

55

60

65

0 3 6 9 12 15 18 21 24 27 30 33 36 39

Months Post-Tx

Mea

n SS

S

Pivotal

UF005-B1

UF005-B2

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• Average of 92% of treated patients under UF005-B2 had symptom improvement at all time points.

• Over 84% of treated patients have had symptom improvement in all groups/protocols at all time points.

• Larger % of patients had symptom improvement under expanded treatment guidelines.

Improvement in Symptom Severity over time

% of Patients with SSS Improvements

89.2%92.2%

85.5%87.5%

85.7%84.1%

86.0% 85.7%

93.1% 93.0%

89.6%

50.0%

60.0%

70.0%

80.0%

90.0%

100.0%

Month-3 Month-6 Month-12 Month-24Months Post ExAblate Tx

% o

f Pat

ient

s

Pivotal UF005-B1 UF005-B2

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Changing treatment guidelines with time

Yes – limited to 2 within a 2 week period

Yes – limited to 2 within a 2 week period

NoSecond treatment session

NoneNone0.5 cm on side closest to serosa

Restricted distance to fibroid capsule

1.5 cm1.5 cm1.5 cmMinimum distance to the serosa

NoneNone1.5 cmMinimum distance to the endometrium

180 minutes180 minutes120 minutesTime restriction first to last sonication

NoneMax Tx 150 cc regardless of number of treatments

Max Tx of 100 cc per fibroid or 150 cc if more

than 1 Fibroid

Volume restriction

Treated volume limited to 50% of all fibroids

Treated Vol. limited to 50% of all fibroids except

submucosal - 33%

Prescribed volume limited to 33% of all

fibroids

Volume restriction as a percentage of fibroid

Commercial Guidelines

Expanded Tx GuidelinesPivotal Study Guidelines

As guidelines relaxed, treatment improved

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Patient is eligiblefor MRgFUS

Recommend Alternative Treatment

HysterectomyMyomectomy

Uterine Artery EmbolizationHormone Therapy

6 fibroids or lessEach > 2cm, < 10 cm in diameterTotal fibroid load < 500 cc -1 txTotal fibroid load <900 cc - 2 txBenign appearance on MRNon-calcifiedLocated in treatable regionNon-pedunculated fibroidFibroid < 12cm beyond skin lineFibroid(s) visible on non-contrast MRINo unidentified pelvic mass outside uterus

All NO Any

YES

Refer to ExAblate Information for

Prescribers for full list of Inclusion/Exclusions and criteria for patient

selection

Patient selection criteria

Evaluate the patient1

Evaluate the fibroids(using MR Screening Exam)2

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AllYES

AnyNO

Contraindication to MR PregnantWeight > 250 lbs Desires future fertilityCannot tolerate prone position Uterine size > 24 weeksScar, clips, IUD in Tx path Hematocrit < 25, ASA > 2Post menopausal Diffuse AdenomyosisAbnormal PAP smear w/in 1 year Contraindication to IVCSAcute pelvic infection Uterine cancerUFS-QOL SSS < 21

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CPT and affiliated APC payment codes

• Category III CPT Codes by AMA CPT

• CPT 0071T Focused ultrasound ablation of uterine leiomyomata, including MR guidance;total leiomyomata volume less than 200cc of tissue

• APC code 0195 - $1595• CPT 0072T Total leiomyomata volume greater or equal to 200cc of

tissue• APC code 0202 - $2454

• Services include: treatment day planning, treatment delivery, MRimage guidance, post-treatment MRI

• Does not include: pre-treatment planning, anesthesia,gadolinium contrast agent, pre-treatment diagnostic tests

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Hospital charge comparison

$16-$23,000$7-$9,000$16-$24,000$7-$9,000$16-$24,000Technical

$4,300$3 -$3,500$3 -$3,500$3 -$3,500$3 -$3,500Professional

UAE

Inpatient

Outpatient

Myomectomy

Outpatient

Myomectomy

InpatientHysterectomy

OutpatientHysterectomy

Inpatient

$16 -$19,000

$10 -$13,000

Technical ProfessionalMRgFUS

$4 -$5,000Complex (CPT 0072T)

$3 -$3,500Simple (CPT 0071T)

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Retreatment rates after uterine fibroid treatments

1.. Marret H, Cottier JP, Alonso AM, Giraudeau B, Body G, Herbreteau D. Predictive factors for fibroids recurrence after uterine artery embolisation, BJOG 2005, 112:461-465

2. Spies JB, Myers ER, Worthington-Kirsch R, Mulgund J, Goodwin S, Mauro M, The Fibroid Registry, Obstetrics & Gynecology, 2005, 106:1309-1318.

3. Broder MS, Goodwin S, Chen G. Comparison of long-term outcomes of myomectomy and uterine artery embolization, Obstetrics & Gynecology, 2002, 100:864-868.

4. Hanafi M. Predictors of Leiomyoma recurrence After Myometomy, Obstetrics & Gynecology, 2005, 105:877-881.

5. Subramanian S, Clark MA, Isaacson K. Outcome and resource use associated with myomectomy, Obstetrics & Gynecology, 2001, 98:583-587.

6. Fedele L, Parazzini F, Luchini L, Mezzopane R, Tozzi L, Villa L. Recurrence of fibroids after myomectomy: a transvaginal ultrasonographic study, Hum Reprod, 1995, 10:1795-1796.

7. Stewart EH, Faur AV, Wise LA, Reilly RJ, Harlow BL. Predictors of Subsequent Surgery for Uterine Leiomyomata After Abdominal Myomectomy, Obstetrics & Gynecology, 2002, 99:426-432.

8. Rossetti A, Sizzi O, Soranna L. Long-term results of laparoscopic myomectomy: recurrence rate in comparison with abdominal myomectomy, Hum Reprod, 2001, 16:770-774.

9. Doridot V, Dubuisson JB, Chapron C, Fauconnier A, Babaki-Fard K. Recurrence of leiomymomata after laparoscopic myomectomy, J. Am. Assoc. Gynecol. Laparosc., 2001, 8:495-500.

10. ExAblate ® 2000 for the treatment of uterine fibroids semi-annual report to FDA, June 2006l report

7.8%14%MRgFUS

2 – 13.7%1.2 – 16%UAE

0 – 11%2.1 – 37%Myomectomy

HysterectomyRetreatment

(not hysterectomy)

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Clinical partners

St. Mary’s HospitalImperial CollegeLondon, UK

Breastopia Namba HospitalMiyazaki, Japan

Fukuoka Tokushukai HospitalFukuoka, Japan

Brigham andWomen's HospitalBoston, MA

Weill Medical CollegeCornell UniversityNew York, NYExAblate of Long IslandGreat Neck, NY

Charité HospitalHumboldt UniversityBerlin, Germany

Beverly Tower WilshireBeverly Hills, CA

Sheba Medical CenterTel Aviv, Israel

Semmelweis MedicalBudapest, Hungary

Iseikai Hospital (Osaka University)Osaka, Japan

University MRIBoca Raton, FL

Shinsuma Hospital (Kobe University)Kobe, Japan

Lahey ClinicBurlington, MA

Mayo ClinicRochester, MN

Virtua HealthMt. Holly, NJ

Itabashi Chuo HospitalTokyo, Japan

Amour ClinicYokohama, Japan

UCSDSan Diego, CA

Aizu Chuo HospitalAizuwakamatsu, Japan

ExAblate of DallasPlano, Tx

RNC Rentgenoradiology,Nll Gertsena,NMSC Pirogova-Lyadov,Botkin Medical CenterMoscow, Russia

Seattle RadiologistsSeattle, WA

15 – N. America16 – ROW

Toronto GeneralToronto, Ont. Canada

Central Texas ExAblateAustin, TxSightLineHouston, Tx

KNIKalamazoo MI

KK Women’s and Children;sHospitalSingapore

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Bone TumorsBone Tumors

Liver TumorsLiver Tumors

Breast CancerBreast Cancer

Brain TumorsBrain Tumors

Uterine FibroidsUterine FibroidsProstate CancerProstate Cancer

InSightec research activities

All studies under investigational use

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• Founded in 1999; 130 employees, headquarters near Haifa, Israel; US offices in Dallas, Texas; Asian offices in Beijing, China, and Tokyo, Japan

• Technology developed by GE and InSightec. Available only with GE SIGNA (1.5T and 3T)

• Over 30 patents and other intellectual property

• Awards: • European Union’s 2004 IST grand prize • 2004 Wall St. Journal’s Technology

Innovation Award• 2005 Diagnostic Imaging Technology

Award

• GE Worldwide Distributor

About InSightec

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ExAblate 2000 uterine fibroids bibliography

Smart OC, Hindley JT, Regan L, Gedroyc WMW Magnetic Resonance guided Focused Ultrasound Surgery of Uterine Fibroids – The Tissue Effects of GnRHAgonist Pre-treatment, European J of Radiology, 2006.Stewart EA, Rabinovici J, Tempany C, Inbar Y, Regan L, Gostout B, Hesley G, Kim HS, Hengst S, Gedroyc W Clinical Outcomes of Focused Ultrasound Surgery for the Treatment of Uterine Fibroids, Fertility and Sterility, 2006, 85(1):22-29.Rabinovici J, Inbar Y, Eylon-Cohen S, Schiff E, Hananel A, Freundlich D Pregnancy and Live Birth after Focused Ultrasound Surgery for Symptomatic FocalAdenomyosis: A Case Report, Human Reproduction, 2006, pp. 1-5Fennessy FM, Tempany CM MRI-guided Focused Ultrasound Surgery of Uterine Leiomyomas, Acad Radiol., 2005, 12:1158-1166Hindley J, Gedroyc WM, Regan L, Stewart E, Tempany C, Hynynen K, McDannold N,Inbar Y, Itzchak Y, Rabinovici J, Kim K, Geschwind JF, Hesley G, Gostout B, EhrensteinT, Hengst S, Sklair-Levy M, Shushan A, Jolesz F MRI Guidance of Focused Ultrasound Therapy of Uterine Fibroids: Early Results, AJR, 2004, 183:1713-1719.Yagel S High-Intensity Focused Ultrasound: a Revolution in Non-invasive

Ultrasound Treatment?, Ultrasound Obstet Gynecol, 2004, 23(3):216-7.Stewart EA, Gedroyc W, Tempany CM, Quade B, Inbar Y, Ehrenstein T, Shushan A,Hindley J, Goldin R, David M, Sklair M, Rabinovici J Focused Ultrasound Treatment of Uterine Fibroids: Safety and Feasibility of a Noninvasive ThermoablativeTechnique, Am J Obstet Gynecol, 2003, pp. 48-54Tempany CM, Stewart EA, McDannold N, Quade B, Jolesz F, Hynynen K MRI Guided Focused Ultrasound Surgery (FUS) of Uterine Leiomyomas: A Feasibility Study,Radiology, 2003, 227:897-905.

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References1. Cramer SF, Patel A. The frequency of uterine leiomyomas. Am J Clin Pathol 1990; 94(4):435-438.2. AHRQ:Evidence Report/Technology Assessment: Number 34 Management of Uterine Fibroids, 01-E051, 2001 3. Spies JB, Coyne K, Guaou GN, Boyle D, Skyrnarz-Murphy K, Gonzalves SM. The UFS-QOL, a new disease-specific symptom and

health-related quality of life questionnaire for leiomyomata. Obstet Gynecol 2002; 99(2):290-3004. Day BD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women:

ultrasound evidence. Am J Obstet Gynecol 2003; 188(1):100-1075. Chavez NF, Stewart EA. Medical treatment of uterine fibroids. Clin Obstet Gynecol 2001; 44(2):372-384.6. Wegienka G, Baird DD, Hertz-Picciotto I, Harlow SD, Steege JF, Hill MC et al. Self-reported heavy bleeding associated with uterine

leiomyomata. Obstet Gynecol 2003; 101(3):431-437.7. Ryan GL, Syrop CH, Van Voorhis BJ. Role, epidemiology, and natural history of benign uterine mass lesions. Clin Obstet Gynecol 2005;

48(2):312-324.8. Lippman SA, Warner M, Samuels S, Olive D, Vercellini P, Eskenazi B. Uterine fibroids and gynecologic pain symptoms in a population-

based study. Fertil Steril 2003; 80(6):1488-1494.9. Stovall DW. Clinical symptomatology of uterine leiomyomas. Clin Obstet Gynecol 2001; 44(2):364-371.10. Farquhar CM, Steiner, CA. Hysterectomy Rates in the United States 1990-1997 Obstetrics & Gynecology, Feb 2002 99:2; 229-23411. Qidwai GI, Caughey AB, Jacoby AF. Obstetric Outcomes in Women With Sonographically Identified Uterine Leiomyomata, Obstet. &

Gynecol., 2006, 107(2):376-382.12. Coronado GD, Marshall LM, Schwartz SM. Complications in Pregnancy, Labor, and Delivery With Uterine Leiomyomas: A Population-

Based Study, Obstet. & Gynecol., 2000, 95(5):764-769.13. Pron G, Cohen M, Soucie J, Garvin G, Vanderburgh L, Bell S. The Ontario Uterine Fibroid Embolization Trial. Part 1. Baseline patient

characteristics, fibroid burden, and impact on life. Fertil Steril 2003; 79(1):112-119.14. Hartmann K, Wu, E, Birmbaum H, Ben-Hamadi R, Spalding J Stang, P, Annual Costs Associated with Clinically detected uterine fibroids:

An employer’s perspective. ACOG 2006 poster, accepted for publication15. Goodwin SC, Bradley LD, Lipman JC, Stweart EA, Nosher JL, Sterling KM, Barth MH, Siskin GP, Shlansky-Goldberg RD. Uterine artery

embolization versus myomectomy: a multicenter comparative study. Fertil Steril. 2006 Jan;85(1):14-21 16. Smith WJ, Upton E, Shuster EJ, Klein AJ, Schwartz, ML. Patient satisfaction and disease specific quality of life after uterine artery

embolization. Am J Obstet Gynecol. 2004, 190:1697-1706

17. Wu, E, Birnbaum H, Farrell M, Spalding J, Stang P, Hartmann K. Lifetime costs of patients with clinically-detected uterine fibroids: an Employer Perspective. ACOG 2006, poster

18. ExAblate® 2000 for the Treatment of Uterine Fibroids Summary of Semi-Annual Report to FDA,June 2006

19. RAND Institute report on UAE