First Combination Pill for Long-Term Endometriosis Approved

The first long-term daily pill to treat endometriosis has been recommended for routine NHS use in England.

In its final draft guidance, the National Institute for Health and Care Excellence (NICE) said relugolix-estradiol-norethisterone should be an option for treating endometriosis symptoms in adults of reproductive age who have not responded to previous medical or surgical treatment.

The drug, also known as relugolix combination therapy (relugolix CT), is the first of its type to be approved for long-term endometriosis treatment by the NHS. Around 1000 women per year are expected to benefit.

Improved Treatment Access

Helen Knight, director of medicines evaluation at NICE, highlighted the convenience of the new treatment. “Instead of travelling to clinics for injections, there is now a daily tablet that can be taken at home,” she said in a statement. “The treatment can also be stopped and started more easily, which is particularly important for those planning to have children and for managing side effects.”

Endometriosis UK welcomed the approval but cautioned that relugolix CT induces a type of “medical menopause” combined with hormone replacement therapy. The charity noted that it may only be suitable for a small proportion of the 1.5 million people affected by the condition.

NICE had already recommended relugolix-estradiol-norethisterone for treating moderate-to-severe symptoms of uterine fibroids.

Clinical Evidence and Effectiveness

Standard treatments for endometriosis include pain relief, hormonal therapies, gonadotropin-releasing hormone (GnRH) agonists, and surgery. 

The regulator emphasised that unlike current injectable GnRH agonist treatments, which can initially cause a flare-up of symptoms, the new tablet works more quickly, combines all necessary hormones in one pill, and returns hormone levels to normal faster when discontinued. The treatment can also be taken at home, reducing the need for clinic visits.

Clinical trials demonstrated that relugolix CT reduced pain compared with placebo. 

The SPIRIT 1 and 2 phase 3 double-blind randomised controlled trials assessed its effectiveness in pre-menopausal adults aged 18-50 years with moderate-to-severe endometriosis-related pain. 

The two co-primary outcomes were the proportion of people with dysmenorrhoea or non-menstrual pelvic pain whose condition responded to treatment. For those with dysmenorrhoea, a response was seen in 75% of people who had relugolix CT compared with 27% and 30% of people who had placebo at 24 weeks in SPIRIT 1 and SPIRIT 2, respectively. 

For those with non-menstrual pelvic pain, there was a response of 59% and 66% of people who had relugolix CT compared with 40% and 43% of people who had placebo at 24 weeks in SPIRIT 1 and SPIRIT 2, respectively. 

Addressing an Unmet Need

A recent report from the Women and Equalities Committee urged the NHS to “urgently implement a training programme to improve the experience of treatment and diagnosis of reproductive health conditions.” It also stressed that improving early diagnosis, including follow-up appointments, should be a key performance indicator for the Women’s Health Strategy for England.

NICE underlined that there was no cure for endometriosis and that there was an unmet need for long-term and non-invasive treatments to manage its symptoms. 

It pointed out that, although relugolix CT had not been directly compared in a clinical trial with usual treatment, indirect comparisons suggested that it was likely to reduce pelvic pain almost as well as GnRH agonists. However, it was unclear how well relugolix CT worked compared with surgery. 

“This new treatment marks a potential step-change in how we manage endometriosis, putting control back in patients’ hands while ensuring value for the taxpayer,” Knight said. “This convenience not only benefits patients but reduces pressure on NHS services.”

Dr Rob Hicks is a retired NHS doctor. A well-known TV and radio broadcaster, he has written three books and has regularly contributed to national newspapers, magazines, and online. He is based in the UK.