1. Sodium Oxybate in the Treatment of Fibromyalgia Sodium Oxybate in the Treatment of Fibromyalgia: Results from an International Phase 3 Clinical Trial Norman Rosenthal, MD Medical Director Capital Clinical Research Associates Rockville, MD Sodium Oxybate is not FDA approved for the treatment of Fibromyalgia

2. Fibromyalgia (FM) Chronic condition characterized by widespread musculoskeletal pain. Associated symptoms: fatigue, sleep disturbance, tenderness, functional disability, depression and cognitive difficulty. 1 Prevalence of FM 2 - 5% worldwide. 2 Impact of FM on patient function: increased disability and reduced productivity. 3 Associated with high health care costs. 4 1 Mease et al. J Rheum 2009;36(10):2318; 2 Branco et al. Semin Arthritis Rheum. 2009 ePub ahead of press 3 Al-Allaf J Clin Rheum 2007;13:199-201; 4 Boonen A et al. Ann Rheum Dis 2005;64:396-402

3. Current FDA Approved Treatments for FM Pregabalin: anti-convulsant that binds the α2-δ subunit of the voltage-gated Ca 2+ channel; approved in 2007 for the management of FM Duloxetine: selective serotonin and norepinephrine reuptake Inhibitor (SSNRI) approved in 2008 for the management of FM Milnacipran: selective serotonin and norepinephrine reuptake inhibitor (SSNRI) approved in 2009 for the management of FM

4. Sodium Oxybate (SXB) Sodium salt of  -hydroxybutyrate (GHB), an endogenous neurotransmitter and/or neuromodulator and metabolite of GABA 1 Approved for treatment of narcolepsy symptoms (EU, US, Canada) 2 –Standard of care for narcolepsy 3 Approved in some EU countries as an IV anesthetic and for treatment of alcohol withdrawal Increases slow-wave-sleep and reduces sleep disruption 1 1 Pardi et al. CNS Drugs 2006;20:993-1018 2 XYREM ® (sodium oxybate) oral solution, product labeling 3 Morgenthaler TI et al. Sleep 2007; 30:1705-11

5. Study Design - Sodium Oxybate for Fibromyalgia Design: Randomized, double-blind, placebo-controlled, parallel-group design at 108 sites US and EU (n=573) Treatment Groups: – Sodium oxybate 4.5 g/night (SXB4.5g) – Sodium oxybate 6 g/night (SXB6g) – Placebo (PBO) Data on file, Jazz Pharmaceuticals, Inc.

6. Study Objectives Secondary outcomes Patient Function Fibromyalgia Impact Questionnaire (FIQ) Patient’s Report of Improvement Patient Global Impression of Change (PGIC) Fatigue Fatigue VAS Sleep Quality Jenkins Sleep Scale (JSS) Functional Outcomes Sleep Questionnaire (FOSQ) HRQoL (SF-36) Primary outcome Pain VAS ≥30% reduction Data on file, Jazz Pharmaceuticals, Inc.

7. Subject Baseline Disposition & Demographics # of SubjectsPBO SXB 4.5g SXB 6gTotal Screened1544 Randomized (ITT) 188 195 190573 Completed 70% 66%61%66% Dropout Due to AE 6% 15%21%14% Dropout Due to Lack of Efficacy 12%9%10%11% Data on file, Jazz Pharmaceuticals, Inc. Demographic Characteristics Age mean, years (SD) 46.6 (10.7) Gender n(%) 513 (90%) females Race n(%) 524 (91%) Caucasian Body Mass Index, kg/m 2 mean (SD) 27.6 (4.6) Time Since First FM Symptoms, years mean (SD) 9.7 (8.8)

8. Pain VAS Responders at Week 14 (LOCF) PBO (n=183) SXB 4.5 g (n=193) SXB 6 g (n=183) Data on file, Jazz Pharmaceuticals, Inc.

9. Pain VAS- Mean Change from Baseline over Time (LOCF) Data on file, Jazz Pharmaceuticals, Inc.

10. FIQ & PGIC Responders – Week 14 (LOCF) Data on file, Jazz Pharmaceuticals, Inc. FIQPGIC

11. Event Placebo (n=188) SXB 4.5g (n=194) SXB 6g (n=189) Nausea 16 ( 9%) 37 (19%) 40 (21%) Dizziness 3 ( 2%) 23 (12%) 25 (13%) Vomiting 6 ( 3%) 10 ( 5%) 16 (9%) Anxiety 3 ( 2%) 10 ( 5%) 15 ( 8%) Edema, peripheral 4 ( 2%) 3 ( 2%) 12 ( 6%) Somnolence 3 ( 2%) 7 ( 4%) 11 ( 6%) Fatigue 4 (2%)6 (3%)11 (6%) Muscle Spasms2 (1%)8 (4%)10 (5%) Insomnia6 (3%)15 (8%)8 (4%) Data on file, Jazz Pharmaceuticals, Inc. Most Common Treatment-Emergent AEs with incidence ≥ 5% and at least twice the rate of placebo

12. Conclusions - Efficacy Sodium oxybate administration resulted in statistically significant and clinically meaningful improvements in: Pain (≥ 30% and ≥ 50% reduction) ≥ 30% pain reduction seen as early as 1 week Patient Functionality (FIQ ≥ 30%) Patient’s Global Impression of Change (PGIC)

13. Conclusions – Safety Generally well-tolerated Adverse event (AE) profile similar in FM clinical studies to that seen in the narcolepsy population

14. Overall Conclusion Data from this study is comparable with previous Phase 2 and Phase 3 clinical trials of SXB treatment in fibromyalgia. References: 1.Scharf et al. 2003 J Rheum 30(5): 1070-1074. 2.Russell et al. 2009 Arthritis Rheum 60(1):299-309 3.Russell et al 2009 Arthritis Rheum 60 (Suppl 10): 1410 4.Mease et al 2009 Arthritis Rheum 60 (Suppl 10): 1412

15. Disclosures This study was supported by Jazz Pharmaceuticals, Inc. (JPI) Dr. Norman Rosenthal received research support from JPI in conducting this study.

17. Baseline Fibromyalgia Symptom Scores Baseline Statistic* Placebo (n=188) SXB4.5g (n=195) SXB6g (n=190) Pain VAS [0–100mm]72.6 (12.9) 70.5 (13.0) 72.2 (14.0) FIQ Score [0–100]63.7 (14.1) 62.3 (15.2) 62.1 (15.1) Fatigue VAS [0–100mm]73.5 (15.0) 71.1 (15.4) 71.5 (17.2) CGI-s [1–7] 4.3 (1.1) 4.5 (1.0) 4.4 (1.0) JSS Total Score [0–20]15.6 (4.4) 15.0 (4.6) 14.9 (4.7) * Reported as Mean (SD) FIQ=Fibromyalgia Impact Questionnaire; CGI-s=clinical global impression of severity; JSS=Jenkins Sleep Score Data on file, Jazz Pharmaceuticals, Inc

18. Sleep Quality (Jenkins Sleep Score) Results: LS mean change from BL showed that treatment with both doses of SXB had greater reductions in sleep disturbance compared to placebo (both p<0.001). How often in the past month did you: 1.Have trouble falling asleep? 2.Wake up several times per night? 3.Have trouble staying asleep (including waking up too early)? 4.Wake up after your usual amount of sleep feeling tired and worn out? Data on file, Jazz Pharmaceuticals, Inc.

19. GHB and Sodium Oxybate (SXB) History of Medicinal Use GHB widely available in health food stores until banned by FDA (1990) Developed in US as pharmaceutical agent at request of FDA 1 (1994) SXB/GHB approved in – Germany (Somsanit ® ) as an anesthetic – Italy and Austria (Alcover ® ) for alcohol and opiate withdrawal – US, EU, Canada (Xyrem ® )for the treatment of cataplexy in narcolepsy and excessive daytime sleepiness (sch.) EU Schedule IV for medicinal use, non-restricted distribution US ( ) and Canada special distribution; very low rate of abuse (0.039%), dependence (0.016%), and diversion (0.0009%) 1 Standard of care for the treatment of narcolepsy (American Academy of Sleep Medicine, 2007) 2 Scheduled by DEA (2000) 3 1 Wang YG et al. J Clin Sleep Med 2009 5(4):365 2 Mongenthaler TI et al. Sleep 2007; 30:1705-11. 3 Neuman Ariel. Available at: http://leda.law.harvard.edu/leda/data/629/Neuman.html. Accessed March 18, 2008.http://leda.law.harvard.edu/leda/data/629/Neuman.html

20. GHB and Sodium Oxybate (SXB) History of Abuse and Misuse Reported abuse, misuse (including facilitated sexual assault), dependence, respiratory depression, coma, and death (since 1980’s) 1 Drug Abuse Warning Network (DAWN) 2006 report. http://dawninfo.samhsa.gov/files/ED2006/DAWN2k6ED.pdf http://dawninfo.samhsa.gov/files/ED2006/DAWN2k6ED.pdf Accessed April 28, 2008. GHB = gamma-hydroxybutyrate COC = cocaine BZP = benzodiazepine COD = oxycodone/combinations Emergency Department visits 1

21. Post-marketing Data of Sodium Oxybate (Xyrem ® ) 1 Abuse, Misuse, Dependence and Diversion Post-marketing data since Xyrem ® was introduced onto market (2002) through March 2008: – 26,000 patients received SXB –Spontaneous AE reports from 15 countries Abuse: 10 cases (0.039%)* Dependence: 4 cases (0.016%)* Misuse: 2 confirmed cases (0.008%) of SXB-facilitated sexual assault Diversion: 5 incidents (0.009%) † 1 Wang et al. 2009 J Clin Sleep Med; 5(4):365 *DSM-IV criteria † 600,00 bottles distributed during this period