REKOVELLE

What it is

Rekovelle is follitropin delta, a recombinant human follicle-stimulating hormone (FSH) produced in a human cell line by recombinant DNA technology. It is presented as a solution for injection in a pre-filled multidose pen with injection needles. Rekovelle is available in three strengths: 12 micrograms in 0.36 mL, 36 micrograms in 1.08 mL, and 72 micrograms in 2.16 mL.

Approved indications

— Controlled ovarian stimulation for the development of multiple follicles in women undergoing assisted reproductive technologies (ART) such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) cycles.

Dosing overview

For the first treatment cycle, the individual daily dose is determined on the basis of the woman's serum anti-Müllerian hormone (AMH) concentration and her body weight. For women with AMH less than 15 pmol/L the daily dose is 12 micrograms irrespective of body weight. For women with AMH 15 pmol/L or greater the daily dose decreases from 0.19 to 0.10 micrograms per kilogram by increasing AMH concentration. The maximum daily dose for the first treatment cycle is 12 micrograms. In subsequent treatment cycles following an inadequate initial response, the dose may be adjusted to a maximum of 24 micrograms. Dosing with Rekovelle should be initiated on day 2 or 3 after start of menstrual bleeding in a protocol using a gonadotropin-releasing hormone antagonist, or approximately 2 weeks after the start of agonist treatment in a protocol using down-regulation with a GnRH agonist. Treatment should continue until adequate follicular development has been achieved as assessed by monitoring with ultrasound alone or in combination with measurement of serum oestradiol levels. Adequate follicular development is achieved on average by the ninth or tenth day of treatment.

Key safety warnings

Patients undergoing stimulation of follicular growth may experience ovarian enlargement and may be at risk of developing ovarian hyperstimulation syndrome. Adherence to the Rekovelle dose and regimen of administration and careful monitoring of therapy will minimise the incidence of such events. Ovarian hyperstimulation syndrome (OHSS) is a condition that can manifest itself with increasing degrees of severity. It comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can result in an accumulation of fluid in the peritoneal, pleural and, rarely, in the pericardial cavities. Symptoms of severe OHSS may include abdominal pain, discomfort and distension, severe ovarian enlargement, weight gain, dyspnoea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhoea. Very rarely, severe OHSS may be complicated by ovarian torsion or thromboembolic events such as pulmonary embolism, ischaemic stroke or myocardial infarction. Because of the risk of developing OHSS, patients should be followed for at least two weeks after hCG administration. Women with recent or ongoing thromboembolic disease or women with generally recognised risk factors for thromboembolic events, such as personal or family history, severe obesity (body mass index greater than 30 kg/m²) or thrombophilia may have an increased risk of venous or arterial thromboembolic events during or following treatment with gonadotropins. Treatment with gonadotropins may further increase the risk for aggravation or occurrence of such events. In these women, the benefits of gonadotropin administration need to be weighed against the risks. Ovarian torsion has been reported for ART cycles. It may be associated with other risk factors such as OHSS, pregnancy, previous abdominal surgery, past history of ovarian torsion, previous or current ovarian cyst and polycystic ovaries. Damage to the ovary due to reduced blood supply can be limited by early diagnosis and immediate detorsion.

Contraindications

Rekovelle is contraindicated in hypersensitivity to the active substance or to any of the excipients, tumours of the hypothalamus or pituitary gland, ovarian enlargement or ovarian cyst not due to polycystic ovarian syndrome, gynaecological haemorrhages of unknown aetiology, ovarian uterine or mammary carcinoma, and pregnancy and lactation. Rekovelle must not be used when an effective response cannot be obtained, such as primary ovarian failure, malformations of sexual organs incompatible with pregnancy, or fibroid tumours of the uterus incompatible with pregnancy.

PBS listing

Rekovelle 12 micrograms, 36 micrograms and 72 micrograms are each listed on the PBS with streamlined restriction. The ex-manufacturer prices are A$84.03 for the 12 microgram strength, A$252.07 for the 36 microgram strength, and A$504.16 for the 72 microgram strength.

Regulatory history

Rekovelle was first registered on the ARTG on 21 September 2017 in three strengths: 12 micrograms, 36 micrograms and 72 micrograms. In November 2017, the PBAC recommended Rekovelle for assisted reproductive technology (controlled ovarian stimulation) on a cost-minimisation basis against follitropin alfa.