Report on New Patented Drugs - Cetrotide

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 Price Guidelines, for all new active substances introduced after January 1, 2002.

Brand Name: Cetrotide

Generic Name: cetrorelix

DIN: 02247766 - 0.25mg/vial - Injection, 02247767 - 3.0mg/vial - Injection

Patentee: Serono Canada Inc.

Indication - as per product monograph: For the prevention of premature ovulation in patients undergoing controlled ovarian stimulation (COS)

Notice of Compliance: August 13, 2003

Date of First Sale: February 25, 2004

ATC Class: H01CC02
Systemic Hormonal Preparation, Excl. Sex Hormones and Insulins; Pituitary and Hypothalamic Hormones and Analogues; Hypothalamic Hormones; Anti-Gonadotropin-Releasing Hormone

Application of the Guidelines

Summary:

The introductory prices of the Cetrotide drug products were found to be within the Guidelines because the cost of therapy did not exceed the cost of therapy of existing drugs in the therapeutic class comparison and the prices did not exceed the range of prices in other comparator countries where Cetrotide is sold.

Scientific Review:

The PMPRB's Human Drug Advisory Panel (HDAP) recommended that Cetrotide be reviewed as a category 3 new drug product (provides moderate, little or no therapeutic advantage over comparable medicines).

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 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.

Cetrotide is used in assisted reproduction techniques to prevent premature luteinising hormone (LH) surges in women undergoing controlled ovarian stimulation (COS), allowing the follicles to mature for planned oocyte retrieval. The HDAP identified Orgalutran as the most appropriate comparator to Cetrotide. This agent belongs to the same 4th level ATC, shares the same indication and is clinically equivalent in addressing the approved indication.

The PMPRB's 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 Cetrotide and its comparator are based on the respective product monographs and supported by clinical literature.

Price Review:

Under the Guidelines, the introductory price for a new category 3 drug product will be presumed to be excessive if it exceeds the price of all of the comparable drug products in the 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 Cetrotide were within the Guidelines as the cost per treatment did not exceed the cost per treatment of the comparator medicine.

1 PPS, July 2004

In 2004 Cetrotide 0.25mg/mL was also sold in France, Germany, Italy, Sweden, Switzerland, the United Kingdom and the United States, and Cetrotide 3mg/3mL was also sold in France, Germany, Sweden, Switzerland, the United Kingdom and the United States. In compliance with the Guidelines, the price in Canada did not exceed the range of prices in those countries; the price of Cetrotide 0.25mg/mL in Canada was third lowest, below the international median price, and the price of Cetrotide 3mg/3mL was second lowest, below the international median price.

Evidence/References:

The references are available on the PMPRB website, under Patented Medicines; Reports on New Patented Drugs for Human Use; Cetrotide.

The comparators and dosage regimen referred to in the Summary Report have been selected by Board Staff and 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. This publication is also part of the PMPRB's commitment to make its price review process more transparent.

The information contained in the PMPRB's Summary Report 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.

Evidence/References Considered by HDAP

1. Cetrotide. Product Monograph, dated July 23, 2003.

2. Griesinger G, Felberbaum RE, Schultze-Mosgau A, Diedrich K. Gonadotropin-releasing hormone antagonists for assisted reproductive techniques: Are there clinical differences between agents? Drugs 2004;64(6):563-75.

3. Olivennes F, Belaische-Allart J, Emperaire JC, et al. Prospective, randomized, controlled study of in vitro fertilization-embryo transfer with a singe dose of a luteinizing hormone-releasing hormone (LH-RH) antagonist (cetrorelix) or a depot formula of an LH-RH agonist (triptorelin). Fertil Steril 2000;73(2):314-20.

4. Albano C, Felberbaum RE, Smitz J, et al. Ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the luteinizing hormone-releasing hormone (LHRH)-analog cetrorelix and LHRH-agonist buserelin. Hum Reprod 2000;15(3):526-31.

5. Nikolettos N, Al-Hasani S, Felberbaum R, et al. Comparison of cryopreservation outcome with human pronuclear stage oocytes obtained by the GnRH antagonist, cetrorelix, and GnRH agonists. Eur J Obstet Gynecol Reprod Biol 2000;93:91-5.

6. Akman MA, Erden HF, Tosun SB, Bayazit N, Aksoy E, Bahceci M. Comparison of agonistic flare-up-protocol and antagonistic multiple dose protocol in ovarian stimulation of poor responders: results of a prospective randomized trial. Hum Reprod 2001;16(5):868-70.

7. Ludwig M, Felberbaum RE, Devroey P, et al. Significant reduction of the incidence of ovarian hyperstimulation syndrome (OHSS) by using LHRH antagonist cetrorelix (cetrotide) in controlled ovarian stimulation for assisted reproduction. Arch Gynecol Obstet 2000;264:29-32.

8. Diedrich K, Diedrich C, Santos E, et al. Suppression of the endogenous luteinizing hormone surge by gonadotrophin-releasing hormone antagonist cetrorelix during ovarian stimulation. Hum Reprod 1994;9(5):788-91.

9. Olivennes F, Fanchin R, Bouchard P, et al. The single or dual administration of the gonadotrophin-releasing hormone antagonist cetrorelix in an in vitro fertilization-embryo transfer program. Fertil Steril 1994;62(3):468-76.

10. Olivennes F, Fanchin R, Bouchard P, Taieb J, Selva J, Frydman R. Scheduled administration of a gonadotrophin-releasing hormone antagonist (cetrorelix) on day 8 of in-vitro fertilization cycles: a pilot study. Hum Reprod 1995;10(6):1382-6.

11. Albano C, Smitz J, Camus M, Riethmuller-Winzen H, Van Steirteghem A, Devroey P. Comparison of different doses of gonadotropin-releasing hormone antagonist Cetrorelix during controlled ovarian hyperstimulation. Fertil Steril 1997;67(5):917-22.

12. Felberbaum R, Reissman T, Kupker W, et al. Hormone profiles under ovarian stimulation with human menopausal gonadotropin (hMG) and concomitant administration of the gonadotropin releasing hormone (GnRH) antagonist cetrorelix at different dosages. J Assist Reproduct Genet 1996;13(3):216-22.

13. Olivennes F, Alvarez S, Bouchard P, Fanchin R, Salat-Baroux J, Frydman R. The use of GnRH antagonist (cetrorelix) in single dose protocol in IVF-embryo transfer: a dose finding study of 3 versus 2 mg. Hum Reprod 1998;13(9):2411-4.

14. Felberbaum RE, Albano C, Ludwig M, et al. Ovarian stimulation for assisted reproduction with HMG and concomitant midcycle administration of the GnRH antagonist cetrorelix according to the multiple dose protocol: a prospective uncontrolled phase III study. Hum Reprod 2000;15(5):1015-20.

15. Al-Inany H, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception (Cochrane Review). In: The Cochrane Library, Issue 2, 2004. Chichester, UK: John Wiley & Sons, Ltd.

16. Ludwig M, Katalinic A, Diedrich K. Use of GnRH antagonists in ovarian stimulation for assisted reproductive technologies compared to long protocol: Meta-analysis. Arch Gynecol Obstet 2001;265:175-82.

17. Huirne AF, Lambalk CB, vanLoenen ACD et al. Contemporary pharmacological manipulation in assisted reproduction. Drugs 2004;64(3):297-322.

18. Leong D. Current drug therapies for female infertility: Parts 1 and 2. Drug Information Perspectives 2000;20(4) and 2001;21(1).