Report on New Patented Drugs - Enablex

Under its transparency initiative, the PMPRB publishes the results of the reviews of new patented drugs by Board Staff, for purposes of applying the PMPRB's Excessive Price Guidelines (Guidelines) for all new active substances introduced after January 1, 2002.

Brand Name: Enablex

Generic Name: (darifenacin hydrobromide)

DIN: 02273217 (7.5 mg/tablet)
02273225 (15 mg/tablet)

Patentee: Novartis Pharmaceuticals Canada Inc.

Indication - as per product monograph: For the treatment of overactive bladder

Date of Issuance of First Patent(s) Pertaining to the Medicine: November 12, 1996

Notice of Compliance: November 14, 2005
Date of First Sale: April 6, 2006 (7.5 mg/tablet)
April 11, 2006 (15 mg/tablet)

ATC Class: G04BD10
Genito Urinary System and Sex Hormones; Urologicals; Other Urologicals, incl. Antispasmodics; Urinary Antispasmotics

Application of the Guidelines

Summary

The introductory prices of Enablex 7.5 mg/tablet and 15 mg/tablet were found to be within the Guidelines because the daily cost of therapy did not exceed the daily cost of therapy of existing drugs in the therapeutic class comparison and the price did not exceed the range of prices in the other comparator countries listed in the Patented Medicines Regulations, 1994 (Regulations) where Enablex 7.5 mg and 15 mg/tablets were sold.

Scientific Review

The PMPRB's Human Drug Advisory Panel (HDAP) recommended that Enablex be reviewed as a category 3 new medicine (provides moderate, little or no therapeutic advantage).

The Therapeutic Class Comparison (TCC) test of the Guidelines provides that the price of a category 3 new drug product cannot exceed the prices of other drugs that treat the same disease or condition. Comparators are generally selected from among existing drug products in the same 4th level of the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) System that are clinically equivalent in addressing the approved indication. See the PMPRB's Compendium of Guidelines, Policies and Procedures for a more complete description of the Guidelines and the policies on TCCs.

The HDAP identified flavoxate (Urispas), oxybutynin (Ditropan XL, Ditropan Syrup, PMS-Oxybutynin) and tolteridine (Detrol/Detrol LA) as the most appropriate comparators for Enablex (darifenacin). All these agents are administered orally, are indicated for the treatment of overactive bladder in adults and share the same 4th level ATC classification.

The Guidelines provide that the dosage recommended for comparison purposes will normally not be higher than the maximum of the usual recommended dosage. The recommended comparable dosage regimens for Enablex and the comparators are based on their respective product monographs, available comparative clinical trial information as well as guidelines relevant to the subject matter.

Price Review

Under the Guidelines, the introductory price of a new category 3 drug product will be presumed to be excessive if it exceeds the prices of all of the comparable drug products based on a TCC test, or if it exceeds the prices of the same medicine in the seven countries listed in the Patented Medicines Regulations. The prices of Enablex 7.5 mg/tablet and 15 mg/tablet were within the Guidelines as the daily cost of treatment did not exceed the daily cost of treatment of the comparator medicines. Furthermore, the Canadian prices of Enablex were the lowest of the four comparator countries in which they were sold.

Introductory Period (April to June 2006)

1. MEDIS McKesseon Canada, May - July 2007
2. Liste de médicaments, Régie de l'assurance maladie du Québec, 15th Ed., Update 13, February 2006
3. Ontario Drug Benefit Formulary, No. 39, September 2005

Introductory Period (April to June 2006)

1. MEDIS McKesseon Canada, May - July 2007
2. Liste de médicaments, Régie de l'assurance maladie du Québec, 15th Ed., Update 13, February 2006
3. Ontario Drug Benefit Formulary, No. 39, September 2005

Where comparators and dosage regimens are referred to in the Summary Reports, they have been selected by the HDAP for the purpose of carrying out the PMPRB's regulatory mandate, which is to review the prices of patented medicines sold in Canada to ensure that such prices are not excessive. The publication of these reports is also part of the PMPRB's commitment to make its price review process more transparent.

The information contained in the PMPRB's Summary Reports should not be relied upon for any purpose other than its stated purpose and is not to be interpreted as an endorsement, recommendation or approval of any drug, nor is it intended to be relied upon as a substitute for seeking appropriate advice from a qualified health care practitioner.

References - Enablex

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2. Chapple CR. Abrams P. Comparison of darifenacin and oxybutynin in patients with overactive bladder: assessment of ambulatory urodynamics and impact on salivary flow. Eur Urol 2005;48:102-9.

3. Zinner N, Tuttle J, Marks L. Efficacy and tolerability of darifenacin, a muscarinic M3 selective receptor antagonist (M3 SRA), compared with oxybutynin in the treatment of patients with overactive bladder. World J Urol 2005;23:248-52.

4. Haab F, Stewart L, Dwyer P. Darifenacin, an M3 selective receptor antagonist, is an effective and well-tolerated once-daily treatment for overactive bladder. Eur Urol 2004;45:420-9.

5. Hill S, Khullar V, Wyndaele J, et al. Dose response with darifenacin, a novel once-daily M3 selective receptor antagonist for the treatment of overactive bladder: results of a fixed dose study. Int Urogynecol J 2006;17:239-47

6. Steers W, Corcos J, Foote J, et al. An investigation of dose titration with darifenacin, an M3-selective receptor antagonist. BJU Int 2005;95:580-6.

7. Zinner N, Susset J, Gittelman M, et al. Efficacy, tolerability and safety of darifenacin, an M3 selective receptor antagonist: an investigation of warning time in patients with OAB. Int J Clin Pract 2006;60:119-26.

8. Cardozo L, Dixon A. Increased warning time with darifenacin: a new concept in the management of urinary urgency. J Urol 2005;173:1214-8.

9. National Collaborating Centre for Women's and Children's Health. Urinary incontinence: the management of urinary incontinence in women. Draft for consultation. Consultation period 5 May - 29 June 2006. http://www.nice.org.uk/page.aspx?o=311416 (accessed June 28, 2006).

10. Johnson S. Urogenital Concerns. J Obstet Gynaecol Can 2006;28:S33-42.

11. American College of Obstetricians and Gynecologists. Urinary incontinence in women. ObstetGynecol 2005;105(6):1533-45.

12. Ouslander JG. Management of overactive bladder. N Engl J Med 2004;350(8):786-99.

13. Chapple C, Steers W, Norton P, et al. A pooled analysis of three phase III studies to investigate the efficacy, tolerability and safety of darifenacin, a muscarinic M3 selective receptor antagonist, in the treatment of overactive bladder. BJU Int 2005;95:993-1001.
14. Foote J, Glavind K, Kralidis G, et al. Treatment of overactive bladder in the older patient: pooled analysis of three phase III studies of darifenacin, an M3 selective receptor antagonist. Eur Urol 2005;48:471-7.

15. DeBisschop ME, Oliphant CM. Management of urinary incontinence. US Pharmacist 2002;27(2):51-9.

16. Anon. Oxybutynin transdermal (Oxytrol) for overactive bladder. The Medical Letter 2003;45(1156):38-9.

17. Canadian Consensus Conference on Urinary Incontinence: Clinical Practice Guidelines for Adults. 2001 The Canadian Continence Foundation.

18. Product Monograph of Detrol. E-CPS 2005.

19. Product Monograph of Detrol LA. E-CPS 2005.

20. Product Monograph of Ditropan . E-CPS 2005.

21. Product Monograph of Ditropan XL. E-CPS 2005.

22. Product Monograph of Oxytrol. E-CPS 2005.