MHRA licenses first in new class of treatment for patients with endometriosis symptoms in the UK

London, United Kingdom, Wednesday 4 September 2024 – Gedeon Richter UK Ltd. (“Gedeon Richter”) today announced that the Medicines and Healthcare Products Regulatory Agency (MHRA) has granted a licence for Ryeqo    (relugolix 40 mg, estradiol 1 mg, and norethisterone acetate 0.5 mg – herein “relugolix combination therapy”), for the symptomatic treatment of endometriosis in adult women of reproductive age who have a history of previous medical or surgical treatment for their endometriosis.[i] The authorisation makes relugolix combination therapy the first (an oral gonadotropin-releasing hormone [GnRH] receptor antagonist) in a new class of treatment licensed in the UK for these women.¹

“The intense pain associated with endometriosis can be crippling and have a devastating impact on people’s lives, from their work to intimate relationships and mental health,” said Professor Andrew Horne, Director of the Centre for Reproductive Health, University of Edinburgh. “With limited treatments available in the UK, relugolix combination therapy which is taken in a single, once daily tablet may help people take control of their endometriosis-associated pain.”

The MHRA licence is based on outcomes from the Phase 3 SPIRIT programme, which comprised two replicate, 24-week, multicentre, randomised, double-blind, placebo controlled trials (SPIRIT 1 [n=424] and SPIRIT 2 [n=410]).^1,[ii] Pivotal data showed that in both studies, significantly more women achieved pain reduction with relugolix combination therapy versus placebo at 24 weeks.^1,2 In SPIRIT 1, 75% (n=158/212) of women responded[1] to relugolix combination therapy for their dysmenorrhoea (painful cramping, usually in the lower abdomen) compared to 27% (n=57/212) in the placebo arm,^1,2 and in SPIRIT 2, there were 75% (n=155/206) dysmenorrhoea responders compared to 30% (n=62/204) in the placebo arm (co-primary endpoint).^1,2 In SPIRIT 1, 59% (n=124/212) of women responded[2] to relugolix combination therapy for their non-menstrual pelvic pain (NMPP) compared to 40% (n=84/212) in the placebo arm,^1,2 and in SPIRIT 2, there were 66% (n=136/206) NMPP responders compared to 43% (n=87/204) in the placebo arm (co-primary endpoint).^1,2 In an open-label, single-arm, long-term extension study up to 80 weeks [n=802], dysmenorrhoea and NMPP reduction was sustained over 2 years with relugolix combination therapy (co-primary endpoints).^1,[iii] 

The overall incidence of adverse events in the relugolix combination therapy group was 71% (n=151/212) in SPIRIT 1, 81% (n=166/206) in SPIRIT 2 and 74% (n=204/277) in the long-term extension study compared with 66% (n=140/212), 75% (n=153/204) and 78% (n=215/275) respectively in the placebo group.^2,3 Data from the long-term extension study was based on original randomisation in the pivotal SPIRIT 1 and 2 trials and included women receiving relugolix combination therapy or placebo for 24 weeks followed by relugolix combination therapy.³ Headache was the most frequently reported adverse event in all three trials, occurring in 27% (n=57/212) of the relugolix combination therapy group in SPIRIT 1, 39% (n=81/206) in SPIRIT 2 and 14% (n=38/277) in the long-term extension study compared with 22% (n=46/212), 31% (n=64/204) and 14% (n=38/275) respectively in the placebo group.^2,3

“The MHRA’s decision to licence relugolix combination therapy in endometriosis is fantastic news and we are delighted the need for more treatment options has been recognised,” said David Jordan, Medical Director UK and Ireland, Gedeon Richter. “We have been working hard to bring a new way of treating the condition to clinicians and women suffering with painful symptoms and we believe this authorisation will be a welcome step for redefining care. We are now engaging with the relevant health authorities throughout the UK with a view to securing NHS reimbursement as soon as possible.”

Gedeon Richter has initiated discussions with the National Institute of Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC), with decision around the NHS availability of relugolix combination therapy expected to be published in 2025.

[1] Clinically meaningful response was defined as patients achieving a mean reduction from baseline in Numerical Rating Scale score of ≥2.8 for dysmenorrhoea over the last 35 days of treatment, without an increase in analgesic use (ibuprofen or opioid).¹

[2] Clinically meaningful response was defined as patients achieving a mean reduction from baseline in Numerical Rating Scale score of ≥2.1 for NMPP over the last 35 days of treatment, without an increase in analgesic use (ibuprofen or opioid).¹

[i] Ryeqo. Summary of Product Characteristics. 16 July 2024. Available at: https://products.mhra.gov.uk/product/?product=RYEQO%2040%20MG%2F1%20MG%2F0.5%20MG%20FILM-COATED%20TABLETS Last accessed: September 2024  

[ii] Giudice, Linda C et al. Once daily oral relugolix combination therapy versus placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2). Lancet. 2022;399:2267–2279.

[iii] Becker, Christian M et al. Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. Hum Reprod. 2024;39(3):526-537.