OVALEAP

What it is

OVALEAP is a biosimilar medicine to GONAL-f solution for injection . It contains follitropin alfa (rch) (recombinant human follicle stimulating hormone) in strengths of 300 IU/0.5 mL, 450 IU/0.75 mL or 900 IU/1.5 mL . OVALEAP is produced by a Chinese Hamster Ovary cell line transfected with the human FSH subunit gene through recombinant DNA technology . It is supplied as a solution for injection in packs containing 1 glass cartridge and 10 or 20 injection needles .

Approved indications

— Treatment of anovulatory infertility in women who have been unresponsive to clomiphene citrate or where clomiphene citrate is contraindicated . — Controlled ovarian hyperstimulation in women undergoing assisted reproductive technologies . — Stimulation of spermatogenesis in gonadotrophin-deficient men in whom hCG alone is ineffective, with concomitant human chorionic gonadotrophin (hCG) therapy .

Dosing overview

OVALEAP should be administered subcutaneously under the supervision of a physician experienced in the treatment of fertility disorders . Dosing varies by indication.

Key safety warnings

Mild to moderate uncomplicated ovarian enlargement, which may be accompanied by abdominal distension and/or abdominal pain, occurs in approximately 20% of those treated with follitropin and hCG, and generally regresses without treatment within two or three weeks . Patients undergoing superovulation are at increased risk of developing Ovarian Hyperstimulation Syndrome (OHSS), a condition that 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 . OHSS can become a serious complication of human gonadotrophin therapy and sometimes leads to fatal complications if not adequately treated . Thromboembolic events, including thrombophlebitis, pulmonary embolism, stroke and arterial occlusion, have been reported following gonadotrophin therapy, and in rare cases have resulted in death . In patients undergoing induction of ovulation, the incidence of multiple pregnancy is increased compared with natural conception, with the majority of multiple conceptions being twins, and multiple pregnancies, especially higher order, carry an increased risk of adverse maternal and perinatal outcomes .

Contraindications

OVALEAP is contraindicated in cases of prior hypersensitivity to follitropin alfa or to any excipients, and in tumours of the hypothalamus or pituitary gland . In women, FSH therapy is contraindicated in pregnancy and lactation, ovarian enlargement or ovarian cyst of unknown aetiology, gynaecological haemorrhages of unknown aetiology, and ovarian, uterine or breast carcinoma . FSH is contraindicated when an effective response cannot be obtained, such as in women with primary ovarian failure as indicated by high levels of FSH, malformations of sexual organs incompatible with pregnancy, and fibroid tumours of the uterus incompatible with pregnancy . In men, FSH is contraindicated in elevated gonadotrophin levels that indicate primary testicular failure and infertility disorders other than hypogonadotrophic hypogonadism .

PBS listing

OVALEAP is listed on the PBS in three strengths: 300 IU in 0.5 mL multi-dose cartridge (ex-manufacturer price A$86.42), 450 IU in 0.75 mL multi-dose cartridge (ex-manufacturer price A$129.63), and 900 IU in 1.5 mL multi-dose cartridge (ex-manufacturer price A$327.48) . All strengths have streamlined restrictions .

Regulatory history

OVALEAP was first approved on 10 March 2021, with all three strengths listed on the ARTG on that date . The Pharmaceutical Benefits Scheme Advisory Committee recommended OVALEAP in July 2021 for assisted reproductive technology, anovulatory infertility, and infertility .