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Uracyst

A summary of the rationale and clinical evidence

Abbreviated Prescribing Information can be found on the last slide of this presentation.PMR-NOV-2010-0615Date of Preparation: November 2010.

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Uracyst

2% solution of sodium chondroitin sulfate

Medical device

Indicated for the replenishment of the GAG layer in the bladder, for patients with damaged or GAG deficient bladder epithelium

Available in 20ml vials (400mg of chondroitin sulfate per vial)

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Mode of Action

Cost comparison

UracystClinical Evidence

Instillation of Uracyst

Roadmap

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The role of the Glycosaminoglycan layer in PBS/IC

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Hurst et al 19876

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Chondroitin sulfate deficit in PBS/IC bladders

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Mode of action of chondroitin sulfate in PBS/IC

Fate of Texas Red labelled chondroitin sulfate after bladder damage with trypsin

Control bladder Damaged bladder

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Chondroitin sulfate restores the barrier effect9

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400mg chondroitin sulfate may be the optimum dose9

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View Dr Robert Hurst’s Presentation

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Mode of Action

Cost comparison

UracystClinical Evidence

Instillation of Uracyst

Roadmap

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Study 1 - Nickel et al 200810

Aim To assess the efficacy and safety of intravesical 2% chondroitin

sulfate (Uracyst) in the treatment of patients with a clinical diagnosis of IC

Method Fifty-three patients with IC were enrolled in a multicentre,

community-based, open-label study, and received intravesical instillations of Uracyst once a week for six weeks, then once a month for 16 weeks

Endpoints The primary endpoint - the percentage of responders to treatment

at week 10*

* assessed by a Global Response Assessment (GRA) scale

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Study 1Uracyst - Proven efficacy in the treatment of PBS/IC10

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Study 1Uracyst - significantly improves quality of life for patients suffering from PBS/IC10

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View Dr Curtis Nickel’s Presentation

View an interview with Dr Curtis Nickel

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Study 2 - Nickel et al 200911

Aim To assess the efficacy of 6 similar weekly treatments of Uracyst

(2% chondroitin sulfate) versus a placebo control.

Method Sixty-five patients were randomised to receive either 6 once-

weekly treatments of Uracyst or the intravesical placebo control.

Endpoints The primary efficacy endpoint was the percent responders to

treatment. A responder was defined as those subjects who had indicated “markedly improved” or “moderately improved”on a 7 point Global Response Assessment (GRA) scale.

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Study 2Uracyst demonstrates almost twice the response rate compared to placebo11

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Tolerability

Uracyst is well tolerated with no significant safety issues apparent during either efficacy study10,11

No serious adverse events have been reported with clinical use

Most issues tend to arise from complications with the catheterisation process

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Mode of Action

Cost comparison

UracystClinical Evidence

Instillation of Uracyst

Roadmap

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Cost comparison – GAG instillations for PBS/IC

Brand Vial Size Cost per Vial (list price)

Uracyst 20ml £65

Gepan 40ml £68*

Cystistat 50ml £98**

iAluRil 50ml £88***

*Gepan Business Case, de Smit Medical

** Cystistat advertisement, Pliva

***iAluRil advertisement, Aspire Pharma

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Mode of Action

Cost comparison

UracystClinical Evidence

Instillation of Uracyst

Roadmap

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Instillation of Uracyst

Catheter

Uracyst in bladder

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Suggested Uracyst treatment plan

Weekly instillations for 4-6 weeks, then monthly thereafter

Optimum response within 4-6 months

Revert back to weekly treatment in cases of symptom flare-up

More frequent therapy may be required in patients with severe PBS/IC

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Summary

PBS/IC patients often have a specific deficit of chondroitin sulfate on the surface of the bladder wall

Intravesical chondroitin sulfate binds extensively to the damaged bladder wall surface, helping to re-establish the GAG layer - the first-line of defence against urine

Uracyst is effective and well tolerated in the treatment of PBS/IC

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References

1. Screening, treatment and management of interstitial cystitis/painful bladder syndrome. Clinical Proceedings. Association of Reproductive Health Professionals. April 2008.2. Rosenberg M , Newman D and Page S. Interstitial cystitis/painful bladder syndrome: Symptom recognition is key to early identification, treatment. Cleveland Clinic Journal of Medicine. 2007; 74 (S3): S54-S62..3. Hurst RE, Roy J and Parsons C. The role of Glycosaminoglycans in normal bladder physiology and the pathophysiology of interstitial cystitis. Interstitial Cystitis. 1997. Philadelphia. Lippincott-Raven Publishers.4. Kelada E and Jones A. Interstitial cystitis. Arch Gynecol Obstet. 2007; 275:223-229.5. Hurst RE et al. A deficit of proteoglycans on the bladder uroepithelium in interstitial cystitis. European Urology Supplements. 2 (2003) 10-13.6. Hurst RE et al. Functional and structural characteristics of the glycosaminoglycans of the bladder luminal surface. The Journal of Urology. 1987; 138: 433-437.7. Hurst RE et al. A deficit of chondroitin sulfate proteoglycans on the bladder uroepithelium in interstitial cystitis. Urology. 1996;48 (5); 817-821.8. Kyker K, Coffman J and Hurst RE. Exogenous glycosaminoglycans coat damaged bladder surfaces in experimentally damaged mouse bladder. BMC Urology. 2005; 5:4 9. Hauser P et al. Restoring barrier function to acid damaged bladder by intravesical chondroitin sulfate. J Urol 2009; 182: 2477-2482.10. Nickel JC et al. A real-life multicentre clinical practice study to evaluate the efficacy and safety of intravesical chondroitin sulphate for the treatment of interstitial cystitis. BJU International. Epub 3 September 2008.11. Nickel JC et al. Chondroitin sulfate is a promising therapy for interstitial cystitis/painful bladder syndrome (IC/PBS). Abstract P114 presented at NAUA, October 2009. CUAJ 2009; 3(Suppl 3): S170.12. Instillation of Uracyst Information Sheet. Stellar Pharmaceuticals Inc. September 2006.13. Uracyst Package Insert. Stellar Pharmaceuticals. November 2008.14. Interstitial cystitis and Uracyst Patient Information Booklet. Stellar Pharmaceuticals Inc.

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Uracyst Prescribing Information

The full Prescribing Information should be consulted prior to use.Uracyst® Abbreviated Prescribing Information. Description: Each ml of Uracyst contains 20mg sodium chondroitin sulfate (400mg of chondroitin sulfate per 20ml vial). Chondroitin sulfate is an acidic mucopolysaccharide and is one of the glycosaminoglycans (GAGs). The luminal surface of the bladder is coated with a layer of GAGs that provide a protective impermeable barrier to the bladder. Damage to this GAG layer may result in deficiencies to its protective barrier, inducing irritations in the bladder wall. Chondroitin sulfate is an important component of the bladder GAGs that can replenish the deficient GAG layer on the bladder epithelium. Indications: For replenishment of the glycosaminoglycan (GAG) layer in the bladder, for patients with damaged or GAG deficient bladder epithelium. Dosage and administration: Instil 20ml into the bladder after any residual urine has been removed. For optimum results, Uracyst should be used full strength without dilution, and retained in the bladder as long as possible (not less than 30 minutes). Repeat the instillation of 20ml weekly for 4 to 6 weeks, then, monthly thereafter until symptoms are relieved. Most patients benefit from 6 weekly 20ml instillations, then monthly instillations thereafter depending on their symptomatic response. Contraindications: Do not administer to patients with known hypersensitivity to the solution. Warnings: For Bladder Instillation only. Uracyst contains neither preservatives nor antimicrobials; therefore, any unused portion must be discarded. Precautions: Bring the contents of vial to room temperature before use. Adverse effects: No known adverse effects. Short-term discomfort may be caused by the catheterisation process. Legal category: Medical device. CE Number: CE 0473. CE Mark Holder: Stellar Pharmaceuticals Inc, 544 Egerton Street, London, Ontario, Canada N5W 3Z8. Package quantities and price: Single-dose glass vial of 20ml. Packages of four: £260 (UK), €300 (Ireland). Storage: Store 2 to 25oC. Do not freeze. Discard unused portions. Distributed by: Galen Limited. Date of preparation: May 2009.

Galen Limited, Seagoe Industrial Estate, Craigavon, BT63 5UA. Galen Ireland, c/o Allphar Services Ltd, 4045 Kingswood Road, Citywest Business Park, Co Dublin, Ireland. Telephone: +44 (0) 28 3833 4974. Fax: +44 (0) 28 3839 1640. Website: www.galen.co.uk. Email: info@galen.co.uk.

Adverse incidents should be reported. Reporting forms and information can be found at www.mhra.gov.uk or www.imb.ie. Adverse incidents should also be reported to Galen Limited on +44 (0)28 3833 4974 and select the customer services option, or e-mail info@galen.co.uk. Medical information enquiries should also be directed to Galen Limited.