Relugolix/Estradiol/Norethindrone Acetate

Endometriosis can cause severe pain, heavy periods, fatigue, and fertility issues. Credit: LaylaBird via Getty Images. The UK’s National Institute for Health and Care (NICE) has approved Gedeon Richter’s Ryeqo (relugolix–estradiol–norethisterone), a once-daily oral treatment for endometriosis, for use on the National Health Service (NHS). The drug works by blocking gonadotrophin releasing hormone (GnRH) that contributes to endometriosis while simultaneously providing necessary hormone replacement. Unlike traditional GnRH agonists – such as Takeda’s Prostap (leuprorelin) and AstraZeneca’s Zoladex (goserelin) – which are limited to six months of use, Ryeqo can be taken until menopause. NICE estimates that around 1,000 women per year could benefit from the treatment, which has a list price of £72 per 28-day pack. Helen Knight, director of medicines evaluation at NICE, highlighted the benefits of a pill-based treatment: “Instead of travelling to clinics for injections, there is now a daily tablet that can be taken at home. 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, a condition where tissue similar to the womb lining grows outside the uterus, causes severe pain, heavy periods, fatigue and fertility issues. Current treatment options include pain relief, hormonal therapy, and surgery. Ryeqo is now an option for those who have previously undergone medical or surgical treatments but found alternatives like tranexamic acid, hormonal contraceptives, and intrauterine delivery systems ineffective or unsuitable. NICE’s final draft guidance emphasised the need for non-invasive, long-term treatment options for endometriosis symptoms, as there is no cure. Charities, including Endometriosis UK, welcomed the news, but noted that Ryeqo induces a state of “medical menopause” alongside hormone replacement therapy (HRT), meaning it may only be suitable for “a small proportion of the 1.5 million with the disease”. NICE reversed its previous negative stance on the drug after Gedeon Richter provided additional evidence on the drug’s effectiveness and cost-effectiveness. Ryeqo improved endometriosis-associated pain and was well tolerated compared to placebo in the Phase III SPIRIT 1 (NCT03204318) and SPIRIT 2 (NCT03204331) clinical studies, which enrolled over 1,200 women. Beyond the approval of new treatments, Endometriosis UK has called for greater investment in research to find the root cause of the disease, improve management strategies, and to develop a cure. At the Royal Society of Medicine’s Innovation in Women’s Health and Femtech meeting on 3 March 2025, McKinsey partner Anouk Petersen pointed out that despite affecting a similar proportion of the population as diabetes (about 10%), endometriosis receives eight to ten times less funding. A report from McKinsey & Company and the World Economic Forum underscored the economic impact of conditions like endometriosis, finding that while women live longer than men, they spend 25% more of their lives in debilitating health conditions. This has direct productivity consequences, with 60% of the gender health gap occurring during prime working years, contributing to 80% of the economic burden on gross domestic product (GDP). According to GlobalData’s Pharma Intelligence Center, Ryeqo is forecast to generate up to $775m in sales in 2030. GlobalData is the parent company of Pharmaceutical Technology.

The National Institute for Health and Care Excellence (NICE) has recommended Gideon Richter’s Ryeqo (relugolix, estradiol and norethisterone) as the first long-term daily pill for endometriosis. NICE has recommended in final draft guidance that the relugolix combination therapy be used on the NHS in England to treat the symptoms of endometriosis in adults of reproductive age who have had medical or surgical treatment for the chronic condition. The health technology assessment agency’s decision follows an earlier negative recommendation and comes after Gideon provided new evidence on the Ryeqo’s effectiveness and value for money. Affecting approximately 1.5 million women in the UK, endometriosis occurs when tissue similar to the lining of the uterus grows elsewhere in the body. Patients can experience a range of symptoms, including dysmenorrhoea (painful cramping, usually in the lower abdomen), heavy bleeding and pelvic pain. Ryeqo is designed to block the specific hormones that contribute to endometriosis while also providing necessary hormone replacement in a single daily tablet. NICE estimates that around 1,000 patients per year could benefit from the therapy. Helen Knight, director of medicines evaluation at NICE, said Ryeqo “marks a potential step-change in how we manage endometriosis”. She continued: “Instead of travelling to clinics for injections, there is now a daily tablet that can be taken at home. 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.” Among the clinical evidence supporting NICE’s recommendation were positive results from the late-stage SPIRIT programme, in which significantly more patients achieved pain reduction with Ryeqo versus placebo at 24 weeks. In the SPIRIT 1 study, 75% of patients responded to Ryeqo for their dysmenorrhoea compared to 27% in the placebo arm. The same result was seen in SPIRIT 2, with 75% of dysmenorrhoea responders in the Ryeqo cohort compared to 30% for placebo. Additionally, 59% and 66% of patients responded to Ryeqo for their non-menstrual pelvic pain (NMPP) in SPIRIT 1 and 2, respectively, compared to 40% and 43% of those receiving placebo. Positive long-term efficacy data from the SPIRIT open-label extension study, which showed that dysmenorrhoea and NMPP reduction was sustained over two years with Ryeqo treatment, also supported the agency’s decision.