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ISSUE 1 FEBRUARY
New drug

Corifollitropin alfa

Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.

Elonva (Schering-Plough)
refilled syringes containing 100 microgram and 150 microgram/0.5 mL
Approved indication: ovarian stimulation
Australian Medicines Handbook section 10.5

Follicle stimulating hormone is used in the management of infertility. Two recombinant forms are available, follitropin alfa and follitropin beta. Women preparing for in vitro fertilisation need daily injections to stimulate follicular development. To reduce the number of injections, the hormone has been genetically engineered to form corifollitropin which has a more prolonged effect on the ovaries.

Corifollitropin combines follicle stimulating hormone with part of the human chorionic gonadotropin molecule. This extends the time to peak serum concentration and approximately doubles the half-life. A single injection can therefore sustain the growth of multiple follicles for a week. Corifollitropin is distributed and metabolised like follicle stimulating hormone with most of the dose being excreted in the urine. The appropriate dose is determined by the patient's weight.

In a placebo-controlled dose-ranging study of 55 women with anovulatory infertility, the follicular response increased with the dose of corifollitropin. Although a single subcutaneous dose induced a follicular response in 28 of the women, only eight ovulated.1

An open-label study compared different doses of corifollitropin alfa with daily injections of recombinant follicle stimulating hormone. The 99 women who were randomised were preparing for in vitro fertilisation or intracytoplasmatic sperm injection. More oocytes were retrieved from the women given corifollitropin than from the ovaries of women given recombinant follicle stimulating hormone. However, there was no significant difference in the number of good quality embryos produced.2

Corifollitropin and recombinant follicle stimulating hormone were then compared in a double-blind trial involving 1506 women weighing 60–90 kg. The women either had daily injections of follicle stimulating hormone or one injection of corifollitropin followed, after a week, by daily follicle stimulating hormone. Significantly more oocytes were retrieved from the women who had corifollitropin in the first week of treatment.3

Similar results were found in a trial of 396 women weighing 60 kg or less.4

In the trial of women of normal weight, 2.1% of those given corifollitropin discontinued treatment because of serious adverse effects compared with 0.4% of the group given recombinant follicle stimulating hormone. Ovarian hyperstimulation syndrome affected 7% of the corifollitropin group and 6.3% of the control group. Other adverse events also occurred with similar frequencies in each group.3Common adverse effects include pelvic pain, headache, breast symptoms and nausea.

Although, statistically, significantly more oocytes were retrieved from women given corifollitropin rather than recombinant follicle stimulating hormone, the difference between treatments was only 1.2 oocytes. Embryo quality was similar and there was no significant difference in the pregnancy rate. Pregnancies lasting at least 10 weeks occurred in 38.9% of the corifollitropin group and 38.1% of the control group, with multiple pregnancies in 28.2% and 23.1%.3

Read about The Transparency Score manufacturer provided additional useful information

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

 

References

  1. Balen AH, Mulders AG, Fauser BC, Schoot BC, Renier MA, Devroey P, et al. Pharmacodynamics of a single low dose of long-acting recombinant follicle-stimulating hormone (FSH-carboxy terminal peptide, corifollitropin alfa) in women with World Health Organization group II anovulatory infertility. J Clin Endocrinol Metab 2004;89:6297-304.
  2. Devroey P, Fauser BC, Platteau P, Beckers NG, Dhont M, Mannaerts BM. Induction of multiple follicular development by a single dose of long-acting recombinant follicle-stimulating hormone (FSH-CTP, corifollitropin alfa) for controlled ovarian stimulation before in vitro fertilization. J Clin Endocrinol Metab 2004;89:2062-70.
  3. Devroey P, Boostanfar R, Koper NP, Mannaerts BM, Ijzerman-Boon PC, Fauser BC, et al. A double-blind, non-inferiority RCT comparing corifollitropin alfa and recombinant FSH during the first seven days of ovarian stimulation using a GnRH antagonist protocol. Hum Reprod 2009;24:3063-72.
  4. The corifollitropin alfa Ensure study group. Corifollitropin alfa for ovarian stimulation in IVF: a randomized trial in lower-body-weight women. Reprod Biomed Online 2010;21:66-76.