New oral treatment for uterine fibroids

Ryeqo contains 40mg relugolix, 1mg estradiol, and 500 microgram norethisterone acetate. The film-coated tablets are taken once daily.

Relugolix is a GnRH receptor antagonist that inhibits the release of luteinizing hormone and follicle-stimulating hormone, thereby suppressing ovulation. It is combined with estradiol to alleviate symptoms associated with a hypoestrogenic state, and norethisterone to reduce the oestrogen-induced risk of endometrial hyperplasia.

Treatment with Ryeqo usually results in reduced menstrual blood loss or amenorrhoea within the first 2 months of treatment, and provides adequate contraception after being taken as indicated for at least 1 month. Alternative contraception must be used as soon as treatment is discontinued.

Dual X-ray absorptiometry is recommended before starting treatment in patients with risk factors for osteoporosis or bone loss, and after 1 year in all patients. The risk of venous or arterial thromboembolism has not been established but patients should be advised to urgently report symptoms. 

Menstrual blood loss

Researchers assessed the efficacy and safety of the relugolix/estradiol/norethisterone combination in two replicate, randomised, double-blind, placebo-controlled 24-week phase III trials in patients aged 18–50 years with heavy menstrual bleeding associated with uterine fibroids. 

Participants were randomised to receive once-daily placebo, relugolix combination therapy, or delayed relugolix combination therapy (relugolix 40mg as monotherapy, followed by relugolix combination therapy, each for 12 weeks). The primary efficacy endpoint in both trials was the percentage of participants with a response in the relugolix combination therapy group compared with the placebo group. Response was defined as menstrual blood loss less than 80ml and at least 50% less in volume than baseline. 

The investigators randomised 388 women in the first trial and 382 in the second trial. Among patients who received relugolix combination therapy, 73% of those in the first trial and 71% of those in the second trial had a response, compared with 19% and 15%, respectively, of those in the placebo groups (p<0.001 for both comparisons).

Both relugolix combination therapy groups showed significant improvements compared with the placebo groups in six of seven key secondary endpoints, including measures of menstrual blood loss (including amenorrhoea), pain, distress from bleeding and pelvic discomfort, anaemia, and uterine volume, although not fibroid volume.

The incidence of adverse events was similar with relugolix combination therapy and placebo. Bone mineral density was also comparable with relugolix combination therapy and placebo.